Efficacy of cementless porous tantalum tibial components versus cemented tibial components in primary total knee arthroplasty: A meta-analysis.

BACKGROUND: Total knee arthroplasty involves the use of cemented tibial components for fixation. In recent years, cementless porous tantalum tibial components have been increasingly utilized. The aim of this meta-analysis was to compare the efficacy of cementless porous tantalum tibial components with traditional cemented tibial components in terms of postoperative outcomes following total knee arthroplasty. METHODS: Relevant literature was retrieved from Cochrane Library, PubMed, Embase, and Web of Science using the search terms "(trabecular metal OR Porous tantalum)" AND "knee" up to July 2023. The weighted mean difference with a 95% confidence interval was used as the effect size measure to evaluate the functional recovery of the knee joint, radiological analysis, complications, and implant revisions between cementless porous tantalum tibial components and traditional cemented tibial components after total knee arthroplasty. Review Manager 5.3 was utilized to conduct a comparative analysis of all included studies. RESULTS: Nine studies with a total of 1117 patients were included in this meta-analysis, consisting of 447 patients in the porous tantalum group and 670 patients in the cemented group. Radiological analysis demonstrated that the porous tantalum group had better outcomes than the cemented group (P < .05). The combined results for the 5-year and 10-year follow-ups, range of motion, Western Ontario and McMaster University Osteoarthritis Index, complications, and implant revisions showed no significant differences between the porous tantalum and cemented groups. CONCLUSION: The results of the 5-year and 10-year follow-ups indicate that the use of cementless porous tantalum tibial components is comparable to traditional cemented tibial components, with no significant advantages observed. However, at the 5-year follow-up, the porous tantalum group demonstrated a good bone density in the proximal tibia. Future studies with a larger sample size, long-term clinical follow-up, and radiological results are needed to verify the differences between the 2 implants.

The Simplified Thrombo-Inflammatory Score as a Novel Predictor of All-Cause Mortality in Patients with Heart Failure: A Retrospective Cohort Study.

Background: The simplified thrombo-inflammatory score (sTIPS) has recently emerged as a novel prognostic score. Hence, we investigated the prognostic value of sTIPS for predicting long-term mortality in patients with heart failure (HF). Methods: A total of 3741 patients were analyzed in this study. The sTIPS was calculated based on the white blood cell count (WBC) and the mean platelet volume to platelet count (MPV/PC) ratio at admission. The mean follow-up time was 22.75 months. Multivariable Cox regression analyses were used to investigate the associations between the sTIPS and all-cause mortality (ACM). Results: In the whole study population, multivariate Cox regression analysis showed that patients in both the sTIPS 2 and sTIPS 1 groups had significantly increased risk of ACM as compared with patients in the sTIPS 0 group (hazard ratio [HR]=1.706, 95% confidence interval [CI]: 1.405-2.072, P<0.001 and HR = 1.431, 95% CI 1.270-1.612, P<0.001). The same significant trend was observed in heart failure with preserved ejection fraction (HFpEF) patients (sTIPS1 vs sTIPS0: HR = 1.366, 95% CI 1.100-1.697, P = 0.005; sTIPS2 vs sTIPS0: HR = 1.995, 95% CI 1.460-2.725, P<0.001). However, only sTIPS 1 group had a significantly increased the risk of ACM compared to the sTIPS 0 group among patients with HFmrEF (sTIPS1 vs sTIPS0: HR = 1.648, 95% CI 1.238-2.194, P = 0.001) and HFrEF (sTIPS1 vs sTIPS0: HR = 1.322, 95% CI 1.021-1.712, P = 0.035). Conclusion: sTIPS is useful in predicting risk for long-term mortality in patients with HF.

Developmental, Reproduction, and Feeding Preferences of the Sitobion avenae Mediated by Soil Silicon Application.

Silicon occupies an important position in the nutrient requirements of wheat. It has been reported that silicon enhances plant resistance to phytophagous insects. However, only limited research has been carried out on the effects of silicon application to wheat and Sitobion avenae populations. In this study, three silicon fertilizer concentrations were treated for potted wheat seedlings, including 0 g/L, 1 g/L, and 2 g/L of water-soluble silicon fertilizer solution. The effect of silicon application on the developmental period, longevity, reproduction, wing pattern differentiation, and other vital life table parameters of the S. avenae were determined. The cage method and the Petri dish isolated leaf method were used to determine the effect of silicon application on the feeding preference of the winged and wingless aphid. The results showed silicon application had no significant effect on the aphid instar of 1-4; although, 2 g/L silicon fertilizer prolonged the nymph stage and 1 and 2 g/L of silicon application all shortened the adult stage and reduced the longevity and fertility of the aphid. Two instances of silicon application reduced the net reproductive rate (R0), intrinsic rate of increase (rm), and finite rate of increase (λ) of the aphid. A 2 g/L silicon application prolonged the population doubling time (td), significantly reduced the mean generation time (T), and increased the proportion of winged aphids. The results also demonstrated that the selection ratio of winged aphids in wheat leaves treated with 1 g/L and 2 g/L silicon was reduced by 8.61% and 17.88%, respectively. The number of aphids on leaves treated with 2 g/L silicon was significantly reduced at 48 and 72 h of aphids released, and the application of silicon to wheat was detrimental to the feeding preference of S. avenae. Therefore, the application of silicon at 2 g/L to wheat has an inhibitory effect on the life parameters and feeding preference of S. avenae.

Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1ß and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

A C-terminal glutamine recognition mechanism revealed by E3 ligase TRIM7 structures.

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.

Effect of Surface Charge on the Fabrication of Hierarchical Mn-Based Prussian Blue Analogue for Capacitive Desalination.

Multiple and hierarchical manganese (Mn)-based Prussian blue analogues obtained on different substrates are successfully prepared using a universal, facile, and simple strategy. Different functional groups and surface charge distributions on carbon cloth have significant effects on the morphologies and nanostructures of Mn-based Prussian blue analogues, thereby indirectly affecting their physicochemical properties. Combined with the advantages of the modified carbon cloth and the nanostructured Mn-based Prussian blue analogues, the composite with negative surface charge formed by the electronegativity differences shows good electrochemical properties, leading to improvement in charge efficiency during capacitive desalination. An asymmetric device fabricated with Mn-based Prussian blue analogue-modified F-doped carbon cloth as the cathode and acid-treated carbon cloth as the anode presents the highest salt adsorption capacity of 10.92 mg g-1 with a charge efficiency of 82.28% and the lowest energy consumption of 0.45 kW h m-3 at 1 V due to the main influencing factor from the negative surface charge leading to co-ion expulsion boosting the capacitive deionization performance. We provide insights for further exploration of the relationship between second-phase materials and carbon cloth, while offering some guidance for the design and preparation of electrodes for desalination and beyond.

Integrated analysis of genes encoding ATP-dependent chromatin remodellers identifies CHD7 as a potential target for colorectal cancer therapy.

BACKGROUND: Genes participating in chromatin organization and regulation are frequently mutated or dysregulated in cancers. ATP-dependent chromatin remodelers (ATPCRs) play a key role in organizing genomic DNA within chromatin, therefore regulating gene expression. The oncogenic role of ATPCRs and the mechanism involved remains unclear. METHODS: We analyzed the genomic and transcriptional aberrations of the genes encoding ATPCRs in The Cancer Genome Atlas (TCGA) cohort. A series of cellular experiments and mouse tumor-bearing experiments were conducted to reveal the regulatory function of CHD7 on the growth of colorectal cancer cells. RNA-seq and ATAC-seq approaches together with ChIP assays were performed to elucidate the downstream targets and the molecular mechanisms. RESULTS: Our data showed that many ATPCRs represented a high frequency of somatic copy number alterations, widespread somatic mutations, remarkable expression abnormalities, and significant correlation with overall survival, suggesting several somatic driver candidates including chromodomain helicase DNA-binding protein 7 (CHD7) in colorectal cancer. We experimentally demonstrated that CHD7 promotes the growth of colorectal cancer cells in vitro and in vivo. CHD7 can bind to the promoters of target genes to maintain chromatin accessibility and facilitate transcription. We found that CHD7 knockdown downregulates AK4 expression and activates AMPK phosphorylation, thereby promoting the phosphorylation and stability of p53 and leading to the inhibition of the colorectal cancer growth. Our muti-omics analyses of ATPCRs across large-scale cancer specimens identified potential therapeutic targets and our experimental studies revealed a novel CHD7-AK4-AMPK-p53 axis that plays an oncogenic role in colorectal cancer.

CBX8 Together with SET Facilitates Ovarian Carcinoma Growth and Metastasis by Suppressing the Transcription of SUSD2.

Polycomb group proteins are often dysregulated in cancer, leading to disruption of epigenetic landscapes and acquisition of cancer hallmarks. Chromobox 8 (CBX8) is a core component of canonical polycomb repressive complex 1; however, its role in transcriptional regulation and in ovarian carcinoma progression has not been extensively investigated. In this study, we find that CBX8 is upregulated in ovarian cancer. Overexpression and knockdown approaches show that CBX8 facilitates the growth and migration of CAOV3, A2780, and SKOV3 cells in vitro. Consistently, depletion of CBX8 suppresses the growth and metastasis of ovarian carcinoma in vivo. Mechanistically, RNA-sequencing assays together with functional rescue experiments identify a tumor suppressor, SUSD2, as the functional target of CBX8 in ovarian carcinoma cells. Significantly, FLAG affinity coupled with mass spectrometry discovers that CBX8 interacts with a subunit of inhibitor of acetyltransferases (INHAT), SET, which also promotes the growth and migration of A2780 cells. CBX8 and SET cobind to the promoter of SUSD2 to establish H2AK119ub1 and prevent the acetylation of histone H3, resulting in transcriptional suppression of SUSD2. IMPLICATIONS: Our study uncovers a novel mechanism CBX8 explores to execute gene repression, and provides new therapeutic targets for ovarian carcinoma.

Sleep duration trajectory during the transition to adolescence and subsequent risk of non-suicidal self-harm.

Non-suicidal self-harm (NSSH) and chronic insufficient sleep are both major health problems during the transition from childhood to adolescence. We examined to identify sleep duration trajectories from childhood to adolescence and their associations with subsequent risk of NSSH. A cohort of children around the period of pubertal onset (7-9 years old) were followed from 2013 over 6 years. Group-based trajectory modeling was recruited to identify sleep duration trajectories derived from 5 repeated measures. Association between sleep duration trajectories with the risk of NSSH was examined using multivariate logistic regression model. Nonlinear dose-response associations between sleep duration and NSSH risk were also assessed using restricted cubic spline models. Of the 1973 participants included in the study (mean ± SD, 8.1 ± 0.9 years age at baseline, 41.1% female). Three sleep duration trajectories were identified: persistent sleeping ≥ 8 h/day (27.7%), moderately decreasing (60.8%) and rapidly decreasing (11.5%) sleep duration groups. After multivariable adjustment for covariates, compared with the persistent sleeping ≥ 8 h/day group, the odds ratio of NSSH was 2.58 (95% CI 1.92, 3.45) for the moderately decreasing group, and 4.16 (2.86, 6.04) for rapidly decreasing group. In dose-response analysis, sleep duration was associated with NSSH risk in a non-linear fashion (χ2 = 25.16, Pnonlinearity < 0.001). When compared with the reference (sleep duration = 8 h), the ORs (95% CI) for NSSH risks were 3.20 (1.93, 5.29), 2.37 (1.64, 3.41), 1.75 (1.39, 2.20) and 1.30 (1.18, 1.44) for sleep duration at 4 to 7 h, respectively. Also, we found sleep duration at 9 h [0.82 (0.75, 0.89)] and at 10 h [0.72 (0.57, 0.91)] significantly associated with decreased risk of NSSH. Longitudinal sleep duration patterns may assist in identification of adolescents at greatest risk of NSSH in the future, which could lead to improved targeting of prevention and intervention strategies. The findings also highlight a non-linear relationship between sleep duration and NSSH during the transition to adolescence.

Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.

Prolonged parent-child separation and pain in adolescence: The role of HPA-axis genetic variations.

BACKGROUND: Increasing evidence has demonstrated that childhood adversity was a predictor of pain and hypothalamic-pituitary-adrenal (HPA) axis genetic variation is associated with pain risk. This study aims to explore possible effects of prolonged childhood separation from parents and HPA polygenic risk score (PRS) on pain among adolescents in rural China. METHOD: We used data from 219 adolescents in rural area of Fuyang city, Anhui province, China. Parent-child separation was collected through interview and pain intensity was reported using the 11-point Numerical Rating Scale. SNP genotyping was performed using an improved multiplex ligation detection reaction (iMLDR) technique. The PRS was computed based on 3 single nucleotide polymorphisms (SNPs) in 2 genes (FKBP5 and NR3C1) related to HPA-axis stress reactivity. RESULTS: Pain among adolescents separated from both parents scored higher compared to those without parent-child separation, however, this association was only observed in adolescents with moderate to high tertiles of PRS groups (parent-child separation in moderate group vs. no parent-child separation in moderate group: 3.07 vs. 1.57, P < 0.001; parent-child separation in highest group vs. no parent-child separation in highest group: 3.02 vs. 1.26, P < 0.001; parent-child separation in lowest group vs. no parent-child separation in lowest group: 2.34 vs. 1.25, P = 0.225). After controlled for demographic characteristics, psychopathological symptoms, adverse childhood experiences, parental warmth, prolonged childhood parent-child separation increased pain scores by 1.52 points (95% CI:0.72, 2.33) and 1.72 points (95% CI:1.13, 2.31) in moderate and high PRS groups, respectively. CONCLUSION: Our findings suggest that adolescents separated from both parents while carrying more risk alleles related to HPA-axis stress reactivity are at heightened risk of pain.

Pharmacokinetics, tissue distribution and excretion of a novel long-acting human insulin analogue - recombinant insulin LysArg in rats.

As a novel long-acting recombinant human insulin analogue, it is necessary to carry out the preclinical research for insulin LysArg. The purpose of this study was to characterise the pharmacokinetic, tissue distribution and excretion of insulin LysArg and provide a reference for its development. Three methods were used to measure the content of insulin LysArg in biological samples after a single subcutaneous administration in rats, including radioassay, radioassay after precipitation with TCA and separation by HPLC. After Subcutaneous administration of recombinant insulin LysArg 1, 2, 4 U/kg in rats, it showed both Cmax and AUC0-t were positively correlated with the dose. In the meanwhile, after a single subcutaneous administration of recombinant insulin LysArg at 2 U/kg in rats, the amount of radioactivity in most organs was highest at 1.5 h and then decreased gradually, no accumulation was found. The highest level of insulin LysArg was observed in the kidney. Like other macromolecules, insulin LysArg was mainly excreted from urine. The study fully illustrated the pharmacokinetic pattern of insulin LysArg, provided valuable informations to support its further development about safety and toxicology.

Silver-Quantum-Dot-Modified MoO3 and MnO2 Paper-Like Freestanding Films for Flexible Solid-State Asymmetric Supercapacitors.

Free-standing paper-like thin-film electrodes have great potential to boost next-generation power sources with highly flexible, ultrathin, and lightweight requirements. In this work, silver-quantum-dot- (2-5 nm) modified transition metal oxide (including MoO3 and MnO2 ) paper-like electrodes are developed for energy storage applications. Benefitting from the ohmic contact at the interfaces between silver quantum dots and MoO3 nanobelts (or MnO2 nanowires) and the binder-free nature and 0D/1D/2D nanostructured 3D network of the fabricated electrodes, substantial improvements on the electrical conductivity, efficient ionic diffusion, and areal capacitances of the hybrid nanostructure electrodes are observed. With this proposed strategy, the constructed asymmetric supercapacitors, with Ag quantum dots/MoO3 "paper" as anode, Ag quantum dots/MnO2 "paper" as cathode, and neutral Na2 SO4 /polyvinyl alcohol hydrogel as electrolyte, exhibit significantly enhanced energy and power densities in comparison with those of the supercapacitors without modification of Ag quantum dots on electrodes; present excellent cycling stability at different current densities and good flexibility under various bending states; offer possibilities as high-performance power sources with low cost, high safety, and environmental friendly properties.

Molecular Identification, Expression, and Functional Analysis of a General Odorant-Binding Protein 1 of Asian Citrus Psyllid.

For insects, odorant-binding proteins (OBPs) play an essential role in binding and transporting semiochemicals through the sensillum lymph to olfactory receptor neurons within the antennal sensilla. In the present study, the full-length cDNA encoding a general odorant-binding protein 1 (DcitOBP1, accession number KY475564) was cloned from the antennae of Diaphorina citri using RACE-PCR, and qRT-PCR analysis revealed that the DcitOBP1 gene was expressed mainly in the antennae of D. citri. In molecular docking assay, the results showed that DcitOBP1 protein has better binding affinities to the 12 selected host-plant volatile compounds. Then, the recombinant DcitOBP1 protein was expressed in Escherichia coli. After removed His-Tag, the binding properties of purified DcitOBP1 protein to the selected host-plant volatile compounds were investigated in a fluorescence ligand-binding assay, similar, but more obviously binding properties of DcitOBP1 protein result were obtained, the dissociation constant (KD) value of DcitOBP1/1-NPN complex was 6.440 ± 0.521, and the DcitOBP1 protein showed high binding affinities (IC50 < 100 µM) to six of the selected ligands, namely methyl salicylate, α-phellandrene, (1R)-(+)-α-pinene, 3-carene, ß-caryophyllene, and α-caryophyllene. Additionally, the behavior bioassays were also showed that D. citri had significant behavioral responses toward to α-caryophyllene, ß-caryophyllene, (1R)-(+)-α-pinene, and α-phellandrene. Our investigation infer that the DcitOBP1 protein might play a crucial role in host-plant volatile odorants' perception in D. citri, and these results also have been supplied previous insight evidence into the physiological functions of the DcitOBP1 protein of D. citri.

Study of pro-angiogenic activity of astilbin on human umbilical vein endothelial cells in vitro and zebrafish in vivo.

Astilbin is a dihydroflavonol natural product isolated from a variety of food and medicinal herbs (e.g. Smilax glabra Roxb.), and its mechanism of action in vascular pharmacology remains unclear. The aim of this study was to investigate the pro-angiogenic effects of astilbin and its putative mechanism of action. Briefly, our in vitro studies showed a dose-dependent ability of astilbin to increase the ability of HUVECs to proliferate and migrate, and undergo cell invasion and tube formation. Moreover, astilbin significantly increased the expression levels of several major proteins involved in the angiogenesis pathway, e.g. PI3K, Akt, p38 and ERK1/2. Our in vivo studies demonstrated the ability of astilbin to significantly restore the blood vessel loss induced by VRI in a VRI-induced vascular insufficiency zebrafish model. In conclusion, in this study we first demonstrate that astilbin exhibits pro-angiogenic activity in HUVECs and VRI-induced vascular insufficient zebrafish, possibly through the activation of the PI3K/Akt and MAPK/ERK dependent signaling pathways. These findings suggest that astilbin could be further developed as a potential agent in the prevention or treatment of insufficient angiogenesis related diseases in the future.

Pharmacokinetics, tissue distribution, and excretion of FGF-21 following subcutaneous administration in rats.

As one of the fibroblast growth factor (FGF) superfamily, FGF-21 has been extensively investigated for its functions and roles since its discovery. It has been demonstrated to be one of the key regulators for glucose and lipid metabolism, and exhibits beneficial effects on cardiovascular disease. However, studies focusing on its pharmacokinetic behavior in vivo as a novel therapeutic agent have not been reported. In the present study, rapid and sensitive analytical approaches including radioactivity assay and assay after precipitation/separation by high performance liquid chromatography (HPLC) were established to determine the content of FGF-21 tagged with 125 I in plasma, tissue, and excrement. The results indicated that FGF-21 were quickly absorbed into systematic circulation and slowly eliminated; Cmax and exposure increased in a dose-dependent manner, exhibiting a typical linear pharmacokinetic pattern. Tissue distribution also confirmed that the kidney is the primary organ for FGF-21 to be distributed, even though radioactivity of FGF-21 was recovered in all tissues examined. In addition, the results also supported that urinary excretion was the critical route for FGF-21 to be eliminated. The study fully clarifies the pharmacokinetic behavior of FGF-21 and can provide valuable information and support further safety and toxicology development.

Clinicopathological significance of miR-101-3p and c-myc mRNA expression in diffused large B-cell lymphoma.

MiR-101-3p has been suggested to be implicated in the pathogenesis of lymphoma, however little is known regarding clinicopathological significance of its expression in diffused large B-cell lymphoma (DLBCL). In contrast, although c-myc has been extensively studied in DLBCL, no direct evidence concerning clinicopathological significance has been well established, either. Given this, in our present study, to understand the significance of both miR-101-3p and c-myc expression on mRNA level in DLBCL, real-time quantitative PCR was used to detect the expression of miR-101-3p and c-myc on mRNA level in 100 cases of DLBCL samples. Association between expression of miR-101-3p and c-myc and clinicopathological variables available was statistically analyzed using Cross-Table test. It was shown that only significant association was observed between miR-101-3p expression and histopathological subtype and therapeutic regimen, no significant relationship was found with other clinicopathological variables. As for c-myc expression, only significant association was found with gender, IPI, and activity of LDH in serum; No significant relations were found with other clinicopathological variables. Together, our study presents the direct evidence regarding clinicopathological significance of miR-101-3p and c-myc expression in DLBCL, which warrants further confirmation in different cohorts with larger sample sizes.

Cryptolepine derivative-6h inhibits liver fibrosis in TGF-ß1-induced HSC-T6 cells by targeting the Shh pathway.

Liver fibrosis is a worldwide problem with a significant morbidity and mortality. Cryptolepis sanguinolenta (family Periplocaceae) is widely used in West African countries for the treatment of malaria, as well as for some other diseases. However, the role of C. sanguinolenta in hepatic fibrosis is still unknown. It has been reported that Methyl-CpG binding protein 2 (MeCP2) had a high expression in liver fibrosis and played a central role in its pathobiology. Interestingly, we found that a cryptolepine derivative (HZ-6h) could inhibit liver fibrosis by reducing MeCP2 expression, as evidenced by the dramatic downregulation of α-smooth muscle actin (α-SMA) and type I collagen alpha-1 (Col1α1) in protein levels in vitro. Meanwhile, we also found that HZ-6h could reduce the cell viability and promote apoptosis of hepatic stellate cells (HSCs) treated with transforming growth factor beta 1(TGF-ß1). Then, we investigated the potential molecular mechanisms and found that HZ-6h blocked Shh signaling in HSC-T6 cells, resulting in the decreased protein expression of Patched-1 (PTCH-1), Sonic hedgehog (Shh), and glioma-associated oncogene homolog 1 (GLI1). In short, these results indicate that HZ-6h inhibits liver fibrosis by downregulating MeCP2 through the Shh pathway in TGF-ß1-induced HSC-T6 cells.

NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma.

NLRC5, a newly found member of the NLR family and the largest member of nucleotide-binding, has been reported to regulate immune responses and is associated with hepatocellular carcinoma (HCC). We investigated the mechanisms and signaling pathways of NLRC5 in HCC progression. Increased expression of NLRC5, vascular endothelial growth factor-A (VEGF-A) were found in human HCC tissue. There was a positive correlation between NLRC5 and VEGF-A expression and cell proliferation were enhanced in NLRC5-overexpressing HepG2 cells, but inhibited in cells with NLRC5 silencing treatment. Interestingly, we found that up-regulation of NLRC5 also coordinated the activation of PI3K/AKT signaling pathway. An AKT inhibitor LY294002 blocked VEGF-A expression and AKT phosphorylation in HepG2 cells and NLRC5-overexpressing HepG2 cells. These results demonstrate that NLRC5 promotes HCC progression via the AKT/VEGF-A signaling pathway.