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Ethnopharmacological Relevance: Ginkgo biloba L. fruit, also known as Bai Guo, Ya Jiao Zi (in pinyin Chinese), and ginkgo nut (in English), has been used for many years as an important material in Chinese traditional medicine to treat coughs and asthma and as a disinfectant, as described in the Compendium of Materia Medica (Ben Cao Gang Mu, pinyin in Chinese), an old herbal book. Ginkgo nuts are used to treat phlegm-associated asthma, astringent gasp, frequent urination, gonorrhoea and turgidity; consumed raw to reduce phlegm and treat hangovers; and used as a disinfectant and insecticide. A similar record was also found in Sheng Nong's herbal classic (Shen Nong Ben Cao Jing, pinyin in Chinese). Recent research has shown that Ginkgo biloba L. exocarp extract (GBEE) can unblock blood vessels and improve brain function and exhibits antitumour and antibacterial activities., Aim of Study: To investigate the inhibitory effect of Ginkgo biloba L. exocarp extract (GBEE) on methicillin-resistant S. aureus (MRSA) biofilms and assess its associated molecular mechanism., Materials and Methods: The antibacterial effects of GBEE on S. aureus and MRSA were determined using the broth microdilution method. The growth curves of bacteria treated with or without GBEE were generated by measuring the CFU (colony forming unit) of cultures at different time points. The effects of GBEE on bacterial biofilm formation and mature biofilm disruption were determined by crystal violet staining. Quantitative polymerase chain reaction (qPCR) was used to measure the effects of GBEE on the gene expression profiles of MRSA biofilm-related factors at 6, 8, 12, 16 and 24 h., Results: The minimum inhibitory concentration (MIC) of GBEE on S. aureus and MRSA was 4 μg/mL, and the minimum bactericidal concentration (MBC) was 8 μg/ml. Moreover, GBEE (4-12 μg/mL) inhibited S. aureus and MRSA biofilm formation in a dose-dependent manner. Interestingly, GBEE also destroyed mature biofilms of S. aureus and MRSA at 12 μg/ml. The expression of the MRSA biofilm-associated factor icaA and sarA were downregulated after 6 h of treatment with GBEE, while sigB was downregulated after 12 h. MeanwhileMeanwhile, icaR was upregulated at 12 h. In addition, GBEE also downregulated the virulence gene hld and inhibited the synthesis of staphyloxanthin., Conclusions: GBEE has excellent antibacterial effects against S. aureus and MRSA and inhibits their biofilm-forming ability by altering related gene expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Doxorubicin (Adriamycin, ADM) is an antimitotic drug used in the treatment of a wide range of malignant tumors, including acute leukemia, lymphoma, osteosarcoma, breast cancer, and lung cancer. Multidrug resistance-associated proteins (MRPs) are members of a superfamily of ATP-binding cassette (ABC) transporters, which can transport various molecules across extra- and intra-cellular membranes. The aim of this study was to investigate whether there was a correlation between MRP4 and primary ADM resistance in osteosarcoma cells. In this paper, we chose the human osteosarcoma cell line MG63, ADM resistant cell line MG63/DOX, and the patient's primary cell GSF-0686. We checked the ADM sensitivity and cytotoxicity of all the three cells by cell proliferation assay. The intracellular drug concentrations were measured by using LC-MS/MS. We also examined MRP4 gene expression by RT-PCR and Western Blot. We found that the intracellular ADM concentration of the parent osteosarcoma cell line MG63 was higher than the ADM resistant osteosarcoma MG63/DOX cell line or the GSF-0686 cell after ADM treatment (P < 0.05). In addition, MRP4 mRNA and protein levels in ADM resistant osteosarcoma cells were higher than in MG63 cell (P < 0.05). Taking together, this work suggests that overexpression of MRP4 may confer ADM resistance in osteosarcoma cells.

Abstract During coronavirus infection, in addition to the well-known coronavirus genomes and subgenomic mRNAs, an abundance of defective viral genomes (DVGs) can also be synthesized. In this study, we aimed to examine whether DVGs can encode proteins in infected cells. Nanopore direct RNA sequencing and liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis were employed. With the protein databases generated by nanopore direct RNA sequencing and the cell lysates derived from the RNA–protein pull-down assay, six DVG-encoded proteins were identified by LC–MS/MS based on the featured fusion peptides caused by recombination during DVG synthesis. The results suggest that the coronavirus DVGs have the capability to encode proteins. Consequently, future studies determining the biological function of DVG-encoded proteins may contribute to the understanding of their roles in coronavirus pathogenesis and the development of antiviral strategies.

Background: Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. Result: Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. Conclusion: This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus. [ABSTRACT FROM AUTHOR]

The inulin-type fructans in Jerusalem artichoke (Helianthus tuberosus L.) tubers exhibit different degrees of polymerization and are critical for germination. We aimed to characterize the sugar metabolism dynamics in the tubers without bud eyes or shoots (T) and BE/S of indoor- and field-grown Jerusalem artichokes during germination. Ht1-FEH II and Ht1-FEH III (1-fructan exohydrolases II and III, inulin-degrading enzymes) expression increased 5 days after planting indoors, whereas Ht1-FEH II expression increased 72 days after planting in the field in T and BE/S. Ht1-SST (sucrose:sucrose 1-fructosyl transferase, inulin synthesis initiator), and Ht1-FFT (fructan:fructan 1-fructosyl transferase, inulin elongator) expression generally decreased in indoor-grown T. The enzyme activities of 1-FEH and 1-FFT were unchanged during germination in both indoor- and field-grown T and BE/S, whereas 1-SST activity decreased in indoor-grown T, while 1-FEH and 1-FFT activities increased as a function of germination time in BE/S of both indoor- and field-grown tubers. The total soluble sugar content gradually decreased in T after germination indoors or in the field, while at the end of germination, the sucrose and fructan contents decreased, and fructose content increased in the field. The enzyme activities of soluble vacuolar (VI) or neutral invertase (NI) did not change significantly, except at the late germination stage. Sucrose synthase (SS) and sucrose-phosphate synthase (SPS) activities were not significantly changed in T and BE/S in indoor-grown artichokes, while SS activity gradually increased, and SPS activity gradually decreased in field-grown artichokes, alongside sucrose degradation. Compared to T, BE/S generally had higher enzyme activities of 1-FEH and 1-FFT, promoting inulin hydrolysis. This work shows that the process of tuber germination is similar indoors and in the field, and germination studies can therefore be conducted in either environment.

Coronaviruses are able to establish persistence. However, how coronaviruses react to persistence and whether the selected viruses have altered their characteristics remain unclear. In this study, we found that the persistent infection of bovine coronavirus (BCoV), which is in the same genus as SARS-COV-2, led to alterations of genome structure, attenuation of gene expression, and the synthesis of subgenomic mRNA (sgmRNA) with a previously unidentified pattern. Subsequent analyses revealed that the altered genome structures were associated with the attenuation of gene expression. In addition, the genome structure at the 5′ terminus and the cellular environment during the persistence were responsible for the sgmRNA synthesis, solving the previously unanswered question regarding the selection of transcription regulatory sequence for synthesis of BCoV sgmRNA 12.7. Although the BCoV variants (BCoV-p95) selected under the persistence replicated efficiently in cells without persistent infection, its pathogenicity was still lower than that of wild-type (wt) BCoV. Furthermore, in comparison with wt BCoV, the variant BCoV-p95 was not able to efficiently adapt to the challenges of alternative environments, suggesting wt BCoV is genetically robust. We anticipate that the findings derived from this fundamental research can contribute to the disease control and treatments against coronavirus infection including SARS-CoV-2.

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier. [ABSTRACT FROM AUTHOR]

Key message: We find that the MYB family transcription factor, LiMYB108, has a novel function to regulate the floral fragrance affected by light intensity. Floral fragrance determines the commercial value of flowers and is influenced by many environmental factors, especially light intensity. However, the mechanism by which light intensity affects the release of floral fragrance is unclear. Here, we isolated an R2R3-type MYB transcription factor LiMYB108, the expression of which was induced by light intensity and located in the nucleus. Light of 200 and 600 μmol m−1 s−1 significantly increased the expression of LiMYB108, which was consistent with the improving trend of monoterpene synthesis under light. Virus-induced gene silencing (VIGS) of LiMYB108 in Lilium not only significantly inhibited the synthesis of ocimene and linalool, but also decreased the expression of LoTPS1; however, transient overexpression of LiMYB108 exerted opposite effects. Furthermore, yeast one-hybrid assays, dual-luciferase assays, and electrophoretic mobility shift assays (EMSA) demonstrated that LiMYB108 directly activated the expression of LoTPS1 by binding to the MYB binding site (MBS) (CAGTTG). Our findings demonstrate that light intensity triggered the high expression of LiMYB108, and then LiMYB108 as a transcription factor to activate the expression of LoTPS1, thus promoting the synthesis of the ocimene and linalool, which are important components of floral fragrance. These results provide new insights into the effects of light intensity on floral fragrance synthesis. [ABSTRACT FROM AUTHOR]

Lilium is a popular cut flower that is highly favored by consumers due to its snowy white color and strong fragrance, which originates from the release of monoterpenes. However, the underlying molecular mechanism of monoterpene synthesis remains poorly understood. In this study, the content of three main monoterpenes (linalool, ocimene, and myrcene) was examined in Lilium 'Siberia', and RNA sequencing of the 11 stages of flower development was conducted. The biosynthesis of the three monoterpenes increased with flower development, reaching their peak levels at the full flowering stage. Transcriptome data revealed 257,140 unigenes, with an average size of 794 bp, from which 43,934 differentially expressed genes were identified and enriched in the KEGG pathways partly involved in plant hormone signal transduction and monoterpenoid biosynthesis. Furthermore, the essential factor LiMYB305 was identified by WGCNA after the release of the flower fragrance. The transient silencing of LiMYB305 in petals using VIGS technology showed that the mRNA expression levels of LiLiS, LiOcS, and LiMyS were significantly downregulated and that the release of linalool, ocimene, and myrcene had decreased significantly. Y1H, LUC, and EMSA experiments revealed that LiMYB305 directly bound and activated the LiOcS promoter to increase the synthesis of monoterpenes. Taken together, these results provide insight into the molecular mechanism of monoterpene synthesis and provide valuable information to investigate the formation of the flower fragrance in Lilium. [ABSTRACT FROM AUTHOR]

Apple epidermal wax protects plants from environmental stresses, determines fruit gloss and improves postharvest storage quality. However, the molecular mechanisms underlying the biosynthesis and regulation of apple epidermal waxes are not fully understood. In this study, we isolated a MdDEWAX gene from apple, which localized in the nucleus, expressed mainly in apple fruit, and induced by drought. We transformed the MdDEWAX gene into Arabidopsis , and found that heterologous expression of MdDEWAX reduced the accumulation of cuticular waxes in leaves and stems, increased epidermal permeability, the rate of water loss, and the rate of chlorophyll extraction of leaves and stems, altered the sensitivity to ABA, and reduced drought tolerance. Meanwhile, overexpression or silencing of the gene in the epidermis of apple fruits decreased or increased wax content, respectively. This study provides candidate genes for breeding apple cultivars and rootstocks with better drought tolerance. • Heterologous expression of MdDEWAX in Arabidopsis reduces the accumulation of cuticular wax in leaves and stems. • Heterologous expression of MdDEWAX in Arabidopsis enhances permeability and reduces drought tolerance. • Overexpression or silencing of MdDEWAX in the epidermis of apple fruits decreases or increases wax content, respectively. [ABSTRACT FROM AUTHOR]

The increasing drug resistance of pathogenic bacteria is a crisis that threatens public health. Antimicrobial peptides (AMPs) have been suggested to be potentially effective alternatives to solve this problem. Here, we tested housefly Phormicin-derived peptides for effects on Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) infections in vitro and in vivo. A decreased bacterial load of MRSA was observed in the mouse scald model after treatment with Phormicin and in the positive control group (vancomycin). A mouse scrape model indicated that Phormicin helps the host fight drug-resistant MRSA infections. The protective effect of Phormicin on MRSA was confirmed in the Hermetia illucens larvae model. Phormicin also disrupted the formation of S. aureus and MRSA biofilms. Furthermore, this effect coincided with the downregulation of biofilm formation-related gene expression (agrC , sigB , RNAIII , altA , rbf , hla , hld , geh and psmɑ). Notably, virulence genes and several regulatory factors were also altered by Phormicin treatment. Based on these findings, housefly Phormicin helps the host inhibit MRSA infection through effects on biofilm formation and related gene networks. Therefore, housefly Phormicin potential represents a candidate agent for clinical MRSA chemotherapy. Unlabelled Image • Phormicin effectively inhibits MRSA infection in skin scratch or scald mice model and promotes the healing of scald wounds. • Phormicin improves the survival of Hermetia illucens larvae infected with MRSA in vivo. • Phormicin inhibits biofilm formation of Staphylococcus aureus and MRSA. • Phormicin altered gene expression of MRSA biofilm formation and virulence. [ABSTRACT FROM AUTHOR]

Although dramatic progress has been achieved in the understanding and treatment of multiple sclerosis (MS) and ischemic stroke (IS), more precise and instructive support is required for further research. Recent large-scale genome-wide association studies (GWASs) have already revealed risk variants for IS and MS, but the common genetic etiology between MS and IS remains an unresolved issue. This research was designed to overlapping genes between MS and IS and unmask their transcriptional features. We designed a three-section analysis process. Firstly, we computed gene-based analyses of MS GWAS and IS GWAS data sets by VGEAS2. Secondly, overlapping genes of significance were identified in a meta-analysis using the Fisher's procedure. Finally, we performed gene expression analyses to confirm transcriptional changes. We identified 24 shared genes with Bonferroni correction (P combined < 2.31E-04), and five (FOXP1 , CAMK2G , CLEC2D , LBH , and SLC2A4RG) had significant expression differences in MS and IS gene expression omnibus data sets. These meaningful shared genes between IS and MS shed light on the underlying genetic etiologies shared by the diseases. Our results provide a basis for in-depth genomic studies of associations between MS and IS. [ABSTRACT FROM AUTHOR]

It has been shown that the inflammatory cytokine tumor necrosis factor α (TNFα) plays a role in the development of hypertension and end-stage renal diseases. We hypothesize that TNFα contributes to endothelial dysfunction and cardiac and vascular injury in deoxycorticosterone acetate (DOCA)/salt-hypertensive mice. The wild-type or TNFα-deficient mice were uninephrectomized and implanted with DOCA pellet treatment for 5 weeks; the mice were given either tap water or 1% NaCl drinking water. DOCA mice developed hypertension (systolic blood pressure (SBP): 167 ± 5 vs. 110 ± 4 mmHg in control group, p < 0.05), cardiac and vascular hypertrophy, and the impairment of endothelium-dependent relaxation to acetylcholine (EDR). TNFα deficiency improved EDR and lowered cardiac and vascular hypertrophy with a mild reduction in SBP (152 ± 4 vs. 167 ± 5 mmHg in DOCA group, p < 0.05) in DOCA mice. The mRNA expressions of the inflammatory cytokines, including TNFα, interleukin 1β (IL1β), monocyte chemotactic protein 1 (MCP1), and monocyte/macrophage marker F4/80 were significantly increased in the aorta of DOCA-hypertensive mice; TNFα deficiency reduced these inflammatory gene expressions. DOCA-hypertensive mice also exhibited an increase in the vascular oxidative fluorescence intensities, the protein expressions of gp91phox and p22phox, and the fibrotic factors transforming growth factor β and fibronectin. TNFα deficiency reduced oxidative stress and fibrotic protein expressions. The DOCA mice also showed a decrease in the protein expression of eNOS associated with increased miR155 expression; TNFα deficiency prevented a decrease in eNOS expression and an increase in miR155 expression in DOCA mice. These results support the idea that TNFα significantly contributes to vascular inflammation, vascular dysfunction, and injury in hypertension. [ABSTRACT FROM AUTHOR]

Background. Clinical data demonstrated that failure rate of titanium implant in irradiated bone was 2-3 times higher than that in nonirradiated bone and it is difficult to get the ideal results in irradiated bone. Purpose. The aim of the study was to investigate the effects of HBO, BMP2, VEGF165, and combined use of BMP2/VEGF165 on osseointegration and stability of titanium implant in irradiated bone. Materials and Methods. Sixty rabbits were randomly assigned to 5 groups (control group, HBO group, VEGF165 group, BMP2 group, and BMP2/VEGF165 group) after receiving 15 Gy radiation. Implant surgery was performed on tibias eight weeks later. They were sacrificed at two or eight weeks after operation. Implant stability, calcium, and ALP activity in serum, the ratio of bone volume to total volume, the rate of bone growth, and gene expression were assessed. Result. There was no mortality and no implants failed during the experiment. Implant stability was significantly compromised in the control group compared to the other four experimental groups, and the BMP2/VEGF165 group had the highest implant stability. HBO, BMP2, and VEGF165 significantly increased BV/TV and the rate of bone growth, while the BMP2/VEGF165 showed the best effect among groups. The expression of RUNX2 in HBO, BMP2, and VEGF165/BMP2 group was higher than that in the VEGF165 and control groups at two weeks. The expression of OCN in HBO, BMP2, VEGF165, and VEGF165/BMP2 groups was higher than that in the control group, and the gene expression of CD31 was higher in HBO, VEGF165, and BMP2/VEGF165 groups than that in control and BMP2 groups. Conclusion. HBO, BMP2, and VEGF165 could increase bone formation around the implant and improved the implant stability in irradiated bone. The combination use of BMP2 and VEGF165 may be promising in the treatment of implant patients with radiotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. OBJECTIVES: We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). METHODS: The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in > 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. RESULTS: Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. CONCLUSIONS: Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment. [ABSTRACT FROM AUTHOR]

Background MicroRNA-126(miR-126) has been shown to be frequently down-regulated in a variety of malignancies and act as a potential tumor suppressor. However, its correlations with the clinicopathological characters of cervical cancer remain unclear. Methods TaqMan quantitative RT-PCR was used to determine the expression level of miR-126 in tissue samples. The associations of miR-126 expression with clinicopathologic variables were analyzed. Kaplan-Meier survival analysis was performed to analyze the association of miR-126 expression with overall survival (OS) of patients. Univariate and multivariate Cox regression analyses were performed Results miR-126 expression level in human cervical cancer tissues was significantly lower than that in adjacent nontumorous tissues (mean < SD: 0.59 < 0.44 vs. 1.00 < 0.51, P < 0.0001). Decreased miR-126 expression in cervical cancer was found to be significantly associated with lymphatic invasion (P = 0.002), distant metastasis (P < 0.001), FIGO stage (P = 0.009), and histological grade (P = 0.005). Kaplan-Meier analysis showed that patients with lower levels of miR-126 had significantly poorer survival than those with higher expression of this miRNA in patients, with a 5-year OS of 45.7% and 70.9%, respectively (P = 0.002). Multivariate analysis revealed that miR-126 expression (HR = 3.97, 95% CI: 2.01-20.22; P = 0.003) was independently associated with the OS. Conclusion Our data suggests the potential of miR-126 as a prognostic biomarker for cervical cancer. [ABSTRACT FROM AUTHOR]

Berberine has multiple pharmacological activities, such as anti-oxidative, anti-inflammation and anticancer activity. It reduces the proliferation and induces apoptosis in the multiple myeloma cell line, U266. Here we explored the detailed mechanism by analysing the gene expression profiles in U266 treated with or without berberine. DNMT1 and DNMT3B, encoding for a highly conserved member of the DNA methyltransferases, decreased significantly. By dissection of biochemical network database (BNDB) with Kyoto Encyclopaedia of Genes and Genomes (KEGG) annotation, the p53 signalling pathway related genes were altered. By using epigenetic chromatin modification enzymes PCR Array, gene expression microarray, RT-PCR and Bisulphite sequencing, the results show that berberine can repress the expression of DNMT1 and DNMT3B, which triggers hypomethylation of TP53 by changing the DNA methylation level and the alteration of p53 dependent signal pathway in human multiple melanoma cell U266. [ABSTRACT FROM AUTHOR]

Purpose: Ezrin is a cytoskeletal protein involved in tumor growth and invasion. However its prognostic value for survival in patients with solid tumor remains controversial. Methods: Several databases were searched, including Pubmed, Embase and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS). The pooled hazard ratio (HR) or odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: Twenty-seven eligible trials involving 4693 patients were ultimately identified. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive Ezrin expression had an impact on overall survival (OS) [1.95, 95% confidence interval (CI) 1.60–2.39; P<0.001] in all eligible studies and progress free survival (PFS): (2.30 95% CI 1.0–3.61; P = 0.001). Similar results were also observed in subgroup analysis, according to tumor types, regions, patients' number and publication year. Conclusions: Our findings suggested that Ezrin protein expression might be a factor for a poor prognosis in patients with solid tumor. So large well-designed prospective studies are now needed to confirm the clinical utility of Ezrin as an independent prognostic marker. [ABSTRACT FROM AUTHOR]

Background: The significance of ezrin immunoexpression and prognosis for osteosarcoma is still controversial. The aim was to provide a meta-analysis for ezrin immunoexpression and prognostic features of osteosarcoma patients. Methods: A detailed search was made in MEDLINE, EMBASE and the Web of Knowledge for relevant original articles published in English; methodological quality of the included studies was also assessed. Two reviewers extracted data independently. Studies were pooled and summary hazard ratios (HRs) and odds ratio (ORs) with corresponding confidence intervals (CIs) were calculated. Results: Final analysis of 318 patients from 5 eligible studies was performed. Combined HR of ezrin immunohistochemical staining suggested that positive immunoexpression had an unfavorable impact on osteosarcoma patients' overall survival (n = 223 in 4 studies; HR = 4.79; 95% CI: 1.50–15.30; P = 0.008) but not on event-free survival (n = 202 in 3 studies; HR = 1.59; 95% CI: 0.61–4.15; P = 0. 0.342). Combined OR of ezrin immunohistochemical staining indicated that positive immunoexpression was associated with recurrence (n = 134 in 2 studies; OR = 3.79; 95% CI: 1.49–9.64; P = 0.005) but not with serum ALP level (n = 160 in 2 studies; OR = 2.16; 95% CI: 0.09–52.50; P = 0.637) and histological response to neoadjuvant chemotherapy(n = 260 in 4 studies; OR = 0.87; 95% CI: 0.37–2.03; P = 0.740). Conclusions: The results of this meta-analysis suggest that ezrin positive immunoexpression confers a higher risk of recurrence and a worse survival in osteosarcoma patients. Large prospective studies are needed to provide solid data to investigate the precise prognostic significance of ezrin. [ABSTRACT FROM AUTHOR]

Melatonin receptors are members of the G protein-coupled receptor (GPCR) family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A) and MT2 (or Mel1b or MTNR1B) receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C), has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor. [ABSTRACT FROM AUTHOR]

Mercury is a toxic heavy metal that is an environmental and industrial pollutant throughout the world. Mercury exposure leads to many physiopathological injuries in mammals. However, the precise toxicological effects of mercury on pancreatic islets in vivo are still unclear. Here, we investigated whether mercuric compounds can induce dysfunction and damage in the pancreatic islets of mice, as well as the possible mechanisms involved in this process. Mice were treated with methyl mercuric chloride (MeHgCl, 2 mg/kg) and mercuric chloride (HgCl2, 5 mg/kg) for more than 2 consecutive weeks. Our results showed that the blood glucose levels increased and plasma insulin secretions decreased in the mice as a consequence of their exposure. A significant number of TUNEL-positive cells were revealed in the islets of mice that were treated with mercury for 2 consecutive weeks, which was accompanied by changes in the expression of the mRNA of anti-apoptotic (Bcl-2, Mcl-1, and Mdm-2) and apoptotic (p53, caspase-3, and caspase-7) genes. Moreover, plasma malondialdehyde (MDA) levels increased significantly in the mice after treatment with mercuric compounds for 2 consecutive weeks, and the generation of reactive oxygen species (ROS) in the pancreatic islets also markedly increased. In addition, the mRNA expression of genes related to antioxidation, including Nrf2, GPx, and NQO1, were also significantly reduced in these islets. These results indicate that oxidative stress injuries that are induced by mercuric compounds can cause pancreatic islets dysfunction and apoptosis in vivo. [ABSTRACT FROM AUTHOR]

Tissue engineering is thought to be the ideal therapy for bone defect reconstructive treatment. In this study, we present a method of utilizing micro/nano porous polycarbonate membranes (PCMs) as the extracellular matrix to cultivate the human periodontal ligament cells (hPDLCs) and investigate the osteogenic differentiation of those cells. We also compared the osteogenic enhancing abilities of different pore size PCMs. The pore diameters of the candidate membranes are 200 nm, 800 nm, 1200 nm, and 10 μm respectively, and their physical properties are identified. After seeding and cultivating on the PCMs, hPDLCs can be stimulated to undergo osteogenic differentiation, in which the 200 nm PCM is proved to have the most optimal osteo-induction ability. The results of in vivo experiments provide strong evidence suggesting that the hPDLCs stimulated by 200 nm PCM greatly accelerates the healing of bone reconstruction in mice skull defects, as well as promote the process of ectopic osteogenesis. RNA-sequencing was conducted to determine the differential mRNA expression profile during the osteogenesis process of hPDLCs on PCMs. GO and KEGG enrichment analysis were conducted to study the regulatory mechanisms, in which osteogenic marker expression such as Hippo, TGF-β, and PI3K-Akt signaling pathways were significantly up-regulated. The up-regulation indicates the promising potential of nano porous PCMs for promoting osteogenesis for bone regeneration applications. Ultimately, signaling pathways that promote osteogenesis warrants further exploration. • Nano porous polycarbonate membrane (PCM) was used to promote osteogenesis in vitro. • PCM with aperture size of 200 nm had optimal osteo-induction ability. • The osteogenesis stimulated by PCM was stable in vivo. • mRNA expression profiling provided support for the osteogenesis process on PCM [ABSTRACT FROM AUTHOR]

We have investigated the function of endogenous galectin-3 in T cells. Galectin-3-deficient (gal3-/-) CD4+ T cells secreted more IFN-γ and IL-4 than gal3+/+CD4+ T cells after T-cell receptor (TCR) engagement. Galectin-3 was recruited to the cytoplasmic side of the immunological synapse (IS) in activated T cells. In T cells stimulated on supported lipid bilayers, galectin-3 was primarily located at the peripheral supramolecular activation cluster (pSMAC). Gal3+/+ T cells formed central SMAC on lipid bilayers less effectively and adhered to antigen-presenting cells less firmly than gal3-/- T cells, suggesting that galectin-3 destabilizes the IS. Galectin-3 expression was associated with lower levels of early signaling events and phosphotyrosine signals at the pSMAC. Additional data suggest that galectin-3 potentiates down-regulation of TCR in T cells. By yeast two-hybrid screening, we identified as a galectin-3-binding partner, Alix, which is known to be involved in protein transport and regulation of cell surface expression of certain receptors. Co-immunoprecipitation confirmed galectin-3-Alix association and immunofluorescence analysis demonstrated the translocation of Alix to the IS in activated T cells. We conclude that galectin-3 is an inhibitory regulator of T-cell activation and functions intracellularly by promoting TCR down-regulation, possibly through modulating Alix's function at the IS. [ABSTRACT FROM AUTHOR]

Galectin-12 is a member of the galectin family consisting of β-galactoside-binding proteins with conserved carbohydrate recognition domains. This protein is preferentially expressed in peripheral blood leukocytes and adipocytes. We previously showed that galectin-12 is induced by cell cycle block at the G1 phase and causes G1 arrest when overexpressed (Yang, R.-Y., Hsu, D. K., Yu, L., Ni, J., and Liu, F.-T. (2001) J. Biol. Chem. 276, 2025220260). Here, we show that the galectin-12 gene is expressed in mouse preadipocytes and is up-regulated when preadipocytes undergo cell cycle arrest, concomitant with acquisition of the competence to undergo differentiation in response to adipogenic hormone stimulation. Following a brief down-regulation I day after adipogenic treatment, its expression was once again markedly elevated when cells underwent terminal differentiation. Down-regulation of endogenous galectin-12 expression by RNA interference greatly reduced the expression of the adipogenic transcription factors CCAAT/enhancer-binding protein-β and -α and peroxisome proliferator-activated receptor-γ and severely suppressed adipocyte differentiation as a result of defective adipogenic signaling. We conclude that galectin-12 is required for signal transduction that conveys hormone stimulation to the induction of adipogenic factors essential for adipocyte differentiation. The findings suggest that galectin-12 is a major regulator of adipose tissue development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In poultries, muscle growth is a quantitative trait controlled by multiple genes. The regulatory mechanisms governing muscle tissue growth and development in poultry, particularly during the early stages of growth, are intricate. Through the examination of leg muscle transcripts from Yili geese during various stages of development, this study offers valuable insights into the molecular mechanisms underlying the growth and development of Yili geese. This study aimed to perform a comparative analysis of the histological characteristics of leg muscles and the mRNA expression profiles of leg muscles in Yili geese at different ages (2, 4, 6, 8, and 10 wk). The objective was to identify differentially expressed genes related to muscle development in Yili geese and utilize bioinformatics to predict the potential biological functions of these genes. Through histological studies on leg muscle tissues, it was discerned that male geese at 4 wk exhibit a significantly reduced muscle fiber density in comparison to females (P < 0.01). In contrast, by the time they reach 6, 8, and 10 wk, their muscle fiber diameter and cross-sectional dimensions significantly outpace the females (P < 0.01). With the advancement in age, muscle fiber density tends to decrease. It is worth noting that 4- and 6-wk-old male geese have a substantially elevated muscle fiber density when matched against females (P < 0.01). Conversely, at the age of 10 wk, their muscle fiber density is notably inferior to the females (P < 0.01). Furthermore, male geese exhibit the most rapid increase in muscle fiber diameter and cross-sectional area between 4 and 6 wk of age. The density of muscle fibers in these geese significantly decreases from 4 to 8 wk. In contrast, female geese show the most pronounced growth in muscle fiber diameter and cross-sectional area between 2 and 6 wk, with a swift decline in density following the 6-wk mark, accompanied by a gradual reduction in the rate of muscle fiber growth. A comprehensive analysis of the leg muscle mRNA expression profiles from 12 Yili geese generated a cumulative total of 502,065,268 valid sequence reads, corresponding to a data volume of 75.30 Gb. In a comparative analysis between 4-wk-old and 2-wk-old groups (T4 vs. T2), 8-wk-old and 2-wk-old groups (T8 vs. T2), and 8-wk-old and 4-wk-old groups (T8 vs. T4), we identified 1,700, 1,583, and 221 differentially expressed genes (DEGs), respectively. Differentially expressed genes were significantly enriched in Gene Ontology (GO) terms such as organelle organization, cytoskeletal protein binding, cation transport, myosin complex, and actin cytoskeleton. Among the significantly enriched signaling pathways, 5 pathways were found to be significantly related to growth and development: adhesion patch, extracellular matrix receptor interaction, tight junction, TGF-β signaling pathway, and MAPK signaling pathway, with a total of 38 differentially differentiated genes contained in these 5 pathways, and it was hypothesized that the above pathways as well as the DEGs in the pathways played an important role in the regulation of early growth and development of the Yili goose. This investigation serves as a foundational reference for elucidating the molecular regulatory mechanisms involved in the development of goose muscle. Furthermore, it contributes to the expansion of the theoretical framework concerning the genetic regulation of muscle growth in geese. [ABSTRACT FROM AUTHOR]

Nitraria tangutorun Bobr. has been used for thousands of years as a native folk medicine to alleviate dizziness and neurasthenia due to oxygen. In our previous study, natural antioxidant components (namely, NJBE) were isolated from industrial N. tangutorun Bobr. juice byproducts (NJBE) from the Qinghai-Tibet plateau. The current investigation assessed the effects of NJBE on ischemic stroke in mice and the potential mechanisms. C57BL/6 mice received NJBE (25, 50, or 100 mg/Kg) by gavage for 14 days and then stroke was induced by the middle cerebral artery occlusion (MCAO) model, followed by reperfusion for 72 h. The evaluation of brain infarct size, behavioral tests, and functional assessments was conducted to assess the effects of NJBE after MCAO. Our results suggested that NJBE significantly decreases infarct size, improves neurological deficits, as well as reduces the number of GFAP+ and Iba-1+ cells after MCAO. NJBE inhibited nitric oxide and malondialdehyde production in the ischemic brain. Meanwhile, it attenuated the expressions of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Also, NJBE significantly attenuated the expression levels of proinflammatory indicators, including TNF-α, IL-1β, IL-6, and IL-12. This process was accompanied by the downregulation of TLR4, TRAF6, pIκB/pIκB, and MMP9 expression and the upregulation of claudin-5 expression. NJBE induced improvements in brain injury. The neuroprotective effect of NJBE provides evidence for its potential application in stroke treatment. [ABSTRACT FROM AUTHOR]

Abstract The formation of the spine is a critical stage of mammalian development. The increase of the number of individual axons affects its performance, especially in meat production. To understand the role of miRNAs in sheep vertebrae development, the purpose of this article is to screen candidate microRNAs (miRNAs) associated with sheep spine development. MicroRNAs (miRNAs) are a rich family of small regulatory RNAs that negatively regulate gene expression at the post-transcriptional level. In this study, we used high-throughput sequencing techniques to analyze the microRNAs (miRNAs) expression profiles of L6 (6 lumbar vertebrae) and L7 (7 lumbar vertebrae) in sheep. A total number of 223 miRNAs were detected in the two libraries, and a total of 150 and 148 conserved miRNAs were obtained in L6 and L7, respectively. A total of 5 miRNAs expression differences in L6 compared to L7 (P < 0.05). Of the five obviously differently expressed miRNAs, four miRNAs were down-regulated in the L6 of sheep, and one was up-regulated. In order to further explore the functions of these miRNAs, we predicted the target genes of these differently expressed miRNAs, and obtained 1298 target genes. At the same time, NDRG2 gene, targeted by novel miR-391, which possible plays an important role in the development of the spine. Linkage-integration analysis method was used to construct the interaction network of spinal-associated miRNA and its hypothesized target. In summary, this study provides valuable resources for the transcriptome of multiple vertebral traits in sheep. Highlights • The miRNA profiles of the multiple lumbar spines in sheep are presented. • A miRNA library of normal lumbar spine and multi-lumbar traits were successfully established. • Differentially expressed miRNAs are associated with spine development. • Our findings will improve the understanding of the role of miRNAs in spine development. [ABSTRACT FROM AUTHOR]

Ubiquitin carboxyl terminal hydrolase 1 (UCHL1), a member of the UCH class of DUBs, has been reported as either an oncogene or a tumor suppressor. However, the molecular mechanism underlying the biological function of UCHL1 in osteosarcoma is still unclear. This study was aimed at elucidating the roles of UCHL1 in regulating the biological behavior of osteosarcoma cells. In this study, we found that UCHL1 was elevated in osteosarcoma compared with normal bone tissue. Moreover, UCHL1 expression level was correlated with tumor maximum diameter, high rate of lung metastases and short survival time. Then, we found that knockdown of UCHL1 in osteosarcoma cell MG63 inhibited cell proliferation and significantly increased cell population in the G1 phase. Several cyclins promoting G1/S phase transition were reduced after UCHL1 knockdown, including cell cycle regulator cyclin D1, cyclin E1 and CDK6. Moreover, inhibition of UCHL1 in MG63 cells dramatically induced cell apoptosis. We also found that down-regulation of UCHL1 in MG63 significantly inhibited cell invasion. Then, we found that there was a positive correlation between UCHL1 expression level and the Akt and ERK phosphorylation status. Finally, in vivo data showed that knockdown of UCHL1 inhibited osteosarcoma growth in nude mice. These results indicate that UCHL1 could work as an oncogene and may serve as a promising therapeutic strategy for osteosarcoma. [ABSTRACT FROM AUTHOR]

Esophageal cancer is an aggressive human malignancy with increasing incidence in the developed world. VEGF-C makes crucial contributions to esophageal cancer progression that are not well understood. Here, we report the discovery of regulatory relationship in esophageal cancers between the expression of VEGF-C and cortactin (CTTN), a regulator of the cortical actin cytoskeleton. Upregulation of CTTN expression by VEGF-C enhanced the invasive properties of esophageal squamous cell carcinoma in vitro and tumor metastasis in vivo. Mechanistic investigations showed that VEGF-C increased CTTN expression by downregulating Dicer-mediated maturation of miR326, thereby relieving the suppressive effect of miR326 on CTTN expression. Clinically, expression of Dicer and miR326 correlated with poor prognosis in patients with esophageal cancer. Our findings offer insights into how VEGF-C enhances the robust invasive and metastatic properties of esophageal cancer, which has potential implications for the development of new biomarkers or therapies in this setting. [ABSTRACT FROM AUTHOR]