An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging.

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

Identification of Dof transcription factors in Dendrobium huoshanense and expression pattern under abiotic stresses.

Introduction: DNA-binding with one finger (Dof) transcription factors (TFs) are a unique family of TFs found in higher plants that regulate plant responses to light, hormones, and abiotic stresses. The specific involvement of Dof genes in the response to environmental stresses remains unknown in D. huoshanense. Methods: A total of 22 Dof family genes were identified from the D. huoshanense genome. Results: Chromosome location analysis showed that DhDof genes were distributed on 12 chromosomes, with the largest number of Dof genes located on chromosome 8. The phylogenetic tree revealed that DhDofs could be categorized into 11 distinct subgroups. In addition to the common groups, DhDof4, DhDof5, DhDof17, and the AtDof1.4 ortholog were clustered into the B3 subgroup. Group E was a newly identified branch, among which DhDof6, DhDof7, DhDof8, and DhDof9 were in an independent branch. The conserved motifs and gene structure revealed the differences in motif number and composition of DhDofs. The dof domain near the N-terminus was highly conserved and contained a C2-C2-type zinc finger structure linked with four cysteines. Microsynteny and interspecies collinearity revealed gene duplication events and phylogenetic tree among DhDofs. Large-scale gene duplication had not occurred among the DhDofs genes and only in one pair of genes on chromosome 13. Synteny blocks were found more often between D. huoshanense and its relatives and less often between Oryza sativa and Arabidopsis thaliana. Selection pressure analysis indicated that DhDof genes were subject to purifying selection. Expression profiles and correlation analyses revealed that the Dof gene under hormone treatments showed several different expression patterns. DhDof20 and DhDof21 had the highest expression levels and were co-expressed under MeJA induction. The cis-acting element analysis revealed that each DhDof had several regulatory elements involved in plant growth as well as abiotic stresses. qRT-PCR analysis demonstrated that DhDof2 was the main ABA-responsive gene and DhDof7 was the main cold stress-related gene. IAA suppressed the expression of some Dof candidates, and SA inhibited most of the candidate genes. Discussion: Our results may provide new insights for the further investigation of the Dof genes and the screening of the core stress-resistance genes.

Comparison of the applicability of seven calculation equations of glomerular filtration rate among elderly people in China.

BACKGROUND: At present, estimated glomerular filtration rate (eGFR) remains the most frequently utilized parameter in the evaluation of kidney injury severity. Numerous equations have been formulated based on serum creatinine (Scr) or serum cystatin C (Cysc) levels. However, there is a lack of consensus regarding the efficacy of these equations in assessing eGFR, particularly for elderly individuals in China. This study aimed to evaluate the applicability of the MDRD, MDRDc, CKD-EPI series, BIS1, and FAS equations within the Chinese elderly population. METHODS: A cohort of 298 elderly patients with measured GFR (mGFR) was enrolled. The patients were categorized into three subgroups based on their mGFR levels. The eGFR performance was examined, taking into account bias, interquartile range (IQR), accuracy P30, and root-mean-square error (RMSE). Bland-Altman plots were employed to verify the validity of eGFR. RESULTS: The participants had a median age of 71 years, with 167 (56.0%) being male. Overall, no significant differences in bias were observed among the seven equations (P > 0.05). In terms of IQR, P30, and RMSE, the BIS1 equation demonstrated superior accuracy (14.61, 72.1%, and 13.53, respectively). When mGFR < 30 ml/min/1.73 m2, all equations underestimated the true GFR, with the highest accuracy reaching only 59%. Bland-Altman plots indicated that the BIS1 equation exhibited the highest accuracy, featuring a 95% confidence interval (CI) width of 52.37. CONCLUSIONS: This study suggested that the BIS1 equation stands out as the most applicable for estimating GFR in Chinese elderly patients with normal renal function or only moderate decline. 2020NL-085-03, 2020.08.10, retrospectively registered.

The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.

In Vitro Ferroptotic and Antitumor Effect of Free or Liposome-Encapsulated Artesunate in Papillary Thyroid Cancer Cells.

Papillary thyroid cancer (PTC) is generally treated as an indolent and curable cancer. However, the unavailability of surgery and ineffective radiotherapy persists in PTCs, resulting in poor outcomes and low survival rates. Thus, new chemotherapeutic strategies for PTCs are urgently needed. Resistance to ferroptosis remarkably contributes to cancer occurrence and progression. Artesunate (ART) has been repurposed as an anticancer drug, as it induces cell death in numerous cancers. However, whether ART induces ferroptosis in PTC cells and, consequently, facilitates PTC therapy remains elusive. Furthermore, overcoming the pharmacological limitations of ART is a key requirement to support its clinical application. Herein, we reanalyzed the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to characterize the occurrence of resistance to ferroptosis in thyroid cancer. In vitro results showed that ART induced ferroptosis in PTC cells by increasing the cellular iron content. The encapsulation of ART by liposomes did not alter the efficiency in inducing ferroptosis and inhibiting the invasion and migration of PTC cells compared with direct ART application. Thus, PTC resistance to ferroptosis can be overcome by ART and liposome-encapsulated ART.

An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ.

In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HPAP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HPAP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ. The specificity, sensitivity and serum stability of DTF-HPAP were verified in vitro, and DTF-HPAP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HPAP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.

Exploration of the anti-inflammatory, analgesic, and wound healing activities of Bletilla Striata polysaccharide.

Bletilla Striata (BS) Polysaccharide (BSP) is one of the main components of the traditional Chinese medicinal plant Bletilla striata Rchb. F. BSP has been widely used in antimicrobial and hemostasis treatments in clinics. Despite its use in skin disease treatment and cosmetology, the effects of BSP on wound healing remain unclear. Here we investigated the anti-inflammatory, antioxidant, and analgesic effects of BSP and explored its impact on morphological changes and inflammatory mediators during wound healing. A carrageenan-induced mouse paw edema model was established to evaluate the anti-inflammatory effect of BSP. Antioxidant indicators, including NO, SOD, and MDA, were measured in the blood and liver. The increased pain threshold induced by BSP was also determined using the hot plate test. A mouse excisional wound model was applied to evaluate the wound healing rate, and HE staining and Masson staining were used to detect tissue structure changes. In addition, ELISA was employed to detect the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum. BSP significantly decreased the concentration of NO and MDA in serum and liver while increasing SOD activity. It exhibited a notable improvement in mouse paw edema induced by carrageenan. BSP dose-dependently delayed the appearance of licking behavior in mice, indicating its analgesic effect. Compared to the control group, the wound healing rate was significantly improved in the BSP treatment group. HE and Masson staining results showed that the BSP and 'Jingwanhong' ointment groups had slightly milder inflammatory responses and significantly promoted more new granulation tissue formation. The levels of serum inflammatory mediators TNF-α, IL-1ß, and IL-6 were reduced to varying degrees. The results demonstrated that BSP possesses anti-inflammatory, antioxidant, analgesic, and wound healing properties, and it may promote wound healing through inhibition of inflammatory cytokine synthesis and release.

Antitumor Mechanism and Therapeutic Potential of Cordycepin Derivatives.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipolysis group was introduced at the cordycepin N6 to improve the problem, cordycepin derivatives (3a-4c) were synthesized, and biological evaluation of compounds was studied. In this study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with an IC50 value of 27.57 ± 0.52 µM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in the G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3 and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

Opportunities and challenges: mesenchymal stem cells in the treatment of multiple sclerosis.

Multiple sclerosis (MS) was once considered an untreatable disease. Through years of research, many drugs have been discovered and are widely used for the treatment of MS. However, the current treatment can only alleviate the clinical symptoms of MS and has serious side effects. Mesenchymal stem cells (MSCs) provide neuroprotection by migrating to injured tissues, suppressing inflammation, and fostering neuronal repair. Therefore, MSCs therapy holds great promise for MS treatment. This review aimed to assess the feasibility and safety of use of MSCs in MS treatment as well as its development prospect in clinical treatment by analysing the existing clinical studies.

Lack of association between TNFA and TNFB polymorphisms and the risk of multiple sclerosis: a meta-analysis from 37 studies.

BACKGROUND: Epidemiological studies about the association between genetic polymorphisms in TNFA, TNFB, and IFNG and the risk for multiple sclerosis (MS) have been performed extensively. However, the results are inconclusive. The purpose of this meta-analysis was to evaluate the contribution of the polymorphisms in TNFA, TNFB, and IFNG to the susceptibility of MS. METHODS: The PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched to identify relevant studies up to October 2021. A meta-analysis was performed, and pooled odds ratios (OR) and confidence intervals (CI) were computed using fixed or random effects models. RESULTS: A marginally significant association of the IFNG +874AT genotype with high risk of MS was observed in a heterozygous comparison (OR = 1.51, 95% CI, 1.02-2.23). However, no significant association between the TNFA (-308 G/A, - 238 G/A, and - 376 G/A) and TNFB +252A/G polymorphisms and MS risk was observed both in overall analysis and in subgroup analysis. CONCLUSION: This meta-analysis provides evidence that the TNFA (-308 G/A, - 238 G/A, and - 376 G/A) and TNFB +252A/G polymorphisms were not risk factors for the occurrence of MS. Further studies with larger samples are necessary to reach the concise results about the contribution of other polymorphisms to the risk of MS.

Synthesis and Characterization of Salinomycin-Loaded High-Density Lipoprotein and Its Effects on Cervical Cancer Cells and Cervical Cancer Stem Cells.

BACKGROUND: Cervical cancer stem cells (CCSCs), a small part of tumor population, are one of the important reasons for metastasis and recurrence of cervical cancer. Targeting CCSCs may be an effective way to eliminate tumors. Salinomycin (Sal) has been proved to be an effective anticancer drug in many studies, especially for cancer stem cells (CSCs). However, the cytotoxicity of salinomycin limits its further research as an anticancer drug. High-density lipoprotein (HDL) nanoparticles are an excellent drug carrier, which can reduce the toxicity of Sal, have a certain targeting effect and improve the clinical benefit of Sal. METHODS: Salinomycin-loaded high-density lipoprotein (S-HDL) was synthesized and characterized by various analytical techniques. CD44highCD24low CCSCs were isolated from HeLa cells by magnetic separation. The uptake of HDL nanoparticles was observed by laser confocal microscopy, and the effect of S-HDL on the proliferation of CCCs and CCSCs was detected by cell viability analysis. Genome-wide analysis was used to analyze the effects of S-HDL on the biological processes of CCCs and then cell apoptosis, cell cycle and cell migration were selected for verification. RESULTS: S-HDL had a particle size of 38.98 ± 1.78 nm and an encapsulation efficiency of 50.73 ± 4.29%. Cell uptake analysis showed that HDL nanoparticles could enhance the drug uptake of CCCs and CCSCs and may target CCCs and CCSCs. In cell viability analysis, CCCs and CCSCs showed high sensitivity to S-HDL. S-HDL can more efficiently prevent CCSCs from developing tumorspheres than Sal in tumorsphere formation study. S-HDL had stronger ability to induce cell cycle arrest, promote cell apoptosis and inhibit cell migration compared with free Sal, which was consistent with the results of Genome Wide analysis. CONCLUSION: S-HDL can effectively target and eliminate CCCs and CCSCs, which is a potential drug for the treatment of cervical cancer.

S-equol, a metabolite of dietary soy isoflavones, alleviates lipopolysaccharide-induced depressive-like behavior in mice by inhibiting neuroinflammation and enhancing synaptic plasticity.

Systemic injection with lipopolysaccharide can lead to depressive-like behavior in experimental animals by inducing neuroinflammation and is considered to be a classic model of depression. S-equol is a major metabolite of dietary soy isoflavones with antioxidant and anti-inflammatory effects, and it has many beneficial effects on human health, including alleviation of menopausal symptoms, osteoporosis, cancer, obesity, chronic kidney disease, and cognitive dysfunction. A recent study reported that S-equol inhibited lipopolysaccharide-stimulated neuroinflammation in astrocytes. However, there is no research on the antidepressant-like effects of S-equol. Therefore, the present study was conducted to evaluate the antidepressant-like effects of S-equol in a lipopolysaccharide-induced depression model in mice and explore its underlying mechanisms. Our results demonstrated that treatment with S-equol (10, 20 and 40 mg kg-1) for 19 days markedly reversed the behavior of acute LPS (1.0 mg kg-1) treated mice in sucrose preference, tail suspension and forced swimming tests, exerting antidepressant-like effects. In addition, S-equol administration significantly decreased the levels of pro-inflammatory cytokines (tumor necrosis factor, interleukin-6, interleukin-10, interleukin-1ß), increased the levels of 5-hydroxytryptamine and norepinephrine, and normalized the release of tryptophan and kynurenine in the hippocampi of lipopolysaccharide-treated mice. Moreover, treatment with S-equol significantly up-regulated the expression of synaptic plasticity-related proteins (phospho synapsin, synapsin, postsynaptic density-95) and down-regulated the toll-like receptor 4/nuclear factor kappa B signaling pathway in the hippocampi of lipopolysaccharide-treated mice. These findings demonstrated that S-equol significantly alleviated the depressive-like behavior induced by acute systemic injection of LPS, and its antidepressant action was related to mediation of neuroinflammation via the TLR4/NF-κB signaling pathway, normalization of the monoamine neurotransmitter levels, reversal of tryptophan metabolism dysfunction, and enhancement of synaptic plasticity. The current study provides insight into the potential of S-equol in the prevention of depression.

Complete genome and phylogenetic analysis of bovine papillomavirus type 15 in Southern Xinjiang dairy cow.

BACKGROUND: Bovine papilloma is a neoplastic disease caused by bovine papillomaviruses (BPVs), which were recently divided into 5 genera and at least 24 genotypes. OBJECTIVES: The complete genome sequence of BPV type 15 (BPV Aks-02), a novel putative BPV type from skin samples from infected cows in Southern Xinjiang China, was determined by collecting warty lesions, followed by DNA extraction and amplicon sequencing. METHODS: DNA was analyzed initially by polymerase chain reaction (PCR) using the degenerate primers FAP59 and FAP64. The complete genome sequences of the BPV Aks-02 were amplified by PCR using the amplification primers and sequencing primers. Sequence analysis and phylogenetic analysis were performed using bio-informatic software. RESULTS: The nucleotide sequence of the L1 open reading frame (ORF) of BPV Aks-02 was 75% identity to the L1 ORF of BPV-9 reference strain from GenBank. The complete genome consisted of 7,189 base pairs (G + C content of 42.50%) that encoded 5 early (E8, E7, E1, E2, and E4) and 2 late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and a LxCxE motif. Among the different members of this group, the percentages of the complete genome and ORFs (including 5 early and 2 late ORFs) sequence identity of BPV Aks-02 were closer to the genus Xipapillomavirus 1 of the Xipapillomavirus genus. Phylogenetic analysis and sequence similarities based on the L1 ORF of BPV Aks-02 revealed the same cluster. CONCLUSIONS: The results suggest that BPV type (BPV Aks-02) clustered with members of the Xipapillomavirus genus as BPV 15 and were closely related to Xipapillomavirus 1.

P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury.

BACKGROUND Microglia participate in mediating neuroinflammation in which P2X7R triggered by adenosine triphosphate has a critical effect after spinal cord injury. However, how the P2X7R of microglia regulate neuroinflammation after spinal cord injury is still unclear. The aim of this study was to explore the mechanism by which the P2X7 receptor of microglia regulates neuroinflammation after spinal cord injury in NLRP3 inflammasome-dependent inflammation. MATERIAL AND METHODS Sixt rats were divided into 5 groups: a sham group, a model group, a BzATP group, an A-438079 group, and a BzATP+CY-09 group. Rats in the sham group were only subjected to laminectomy and rats in the other groups were subjected to spinal cord injury followed by treatment with physiological saline, BzATP, A-438079, and BzATP following CY-09, separately. Real-time polymerase chain reaction, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to analyze the scientific hypothesis. RESULTS (i) P2X7R of microglia was upregulated and downregulated by BzATP, and A-438079 was upregulated after spinal cord injury. (ii) Upregulation of P2X7R on microglia is coincident with increase of neuroinflammation after spinal cord injury. (iii) P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation. CONCLUSIONS P2X7R of microglia in spinal cord mediates neuroinflammation by regulating NLRP3 inflammasome-dependent inflammation after spinal cord injury.

High prevalence of Clonorchis sinensis infections and coinfection with hepatitis virus in riverside villages in northeast China.

In China, the prevalence of Clonorchis sinensis (C. sinensis) infections is only evaluated at the provincial level by national sampling surveys, and data from villages and counties are still lacking. In this study, we conducted a cross-sectional survey in 10 villages located along the Lalin River in northeast China. Clonorchiasis was diagnosed using a modified Kato-Katz method that detects the C. sinensis egg in stools. A total of 3,068 persons were screened and 2,911 were recruited for the study. Overall, the prevalence of C. sinensis infection was 29.3%. Among 175 participants who were cured after antiparasitic treatment, 54 (30.86%) were re-infected in this survey. After calibration of potential confounders, male gender, occupation as a farmer, smoking, and occasionally or frequently eating raw fish were independent risk factors for C. sinensis infection. The results of laboratory examinations in the C. sinensis/hepatitis B or C virus co-infection group were similar to those in the hepatitis B or C virus mono-infection groups. In conclusion, C. sinensis is highly endemic in villages along the Lalin River, and the primary route of infection is the consumption of raw freshwater fish. Co-infection with C. sinensis did't aggravate the clinical manifestations of viral hepatitis in this cross-sectional study.

Dynamic Fixation versus Static Fixation in Treatment Effectiveness and Safety for Distal Tibiofibular Syndesmosis Injuries: A Systematic Review and Meta-Analysis.

To compare the effectiveness and safety of dynamic fixation (DF) and static fixation (SF) in distal tibiofibular syndesmosis injuries (DTSI) by a system review and meta-analysis. PubMed, Cochrane, and EMBASE were systematically searched by computer to select clinical randomized controlled trials (RCT) and cohort trials comparing DF and SF in treating patients with DTSI. RCT and cohort trials comparing DF and SF for patients with DTSI were included. Inclusion criteria: (i) prospective or retrospective study of patients with DTSI; (ii) patients were diagnosed as having DTSI by imageology and only received DF treatment or SF treatment; (iii) the study compared DF and SF in DTSI; and (iv) one or more of the following outcomes were reported: ankle joint functional score, surgical complications, malreduction of syndesmosis, and second operations. Exclusion criteria: (i) non-human studies; (ii) DTSI patients accompanied with other complications or other joints injuries; and (iii) full text unavailable. RevMan V5.3 software was used to perform the statistical analysis. Outcomes analyzed by Revman software showed that there were no statistically significant differences between DF and SF in the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score (MD, 1.90; 95% CI, -0.23 to 4.03; P = 0.08; I2 = 0%), Olerud-Molander (OM) score (MD, 1.92; 95% CI, -7.96 to 11.81; P = 0.70; I2 = 55%), incidence of syndesmotic malreduction (RR, 0.19; 95% CI, 0.03 to 1.09; P = 0.06; I2 = 0%), and overall postoperative complication rate (RR, 0.30; 95% CI, 0.09 to 0.99; P = 0.05, I2 = 75%) and the rate of second procedure was significantly lower with DF (RR, 0.17; 95% CI, 0.07 to 0.43; P = 0.0002, I2 = 54%). Compared to SF, DF has an advantage, with a low rate of second procedures to treat DTSI.

A zebrafish (danio rerio) model for high-throughput screening food and drugs with uric acid-lowering activity.

With co-treatment of potassium oxonate (PO) and xanthine sodium salt (XSS), a zebrafish larva model of acute hyperuricemia has been constructed for the first time. The results show PO 200 µM + XSS 10 µM, PO 300 µM + XSS 15 µM, and PO 400 µM + XSS 20 µM can significantly increase the level of uric acid in the zebrafish larvae (P < 0.05), the concentrations as described above can be used to construct the zebrafish larvae model of acute hyperuricemia. At the same time, treatment of allopurinol (APL, one of the hyperuricemia drugs) at 2000 µM (P < 0.001) and treatment of anserine (ASE) at 200 µM (P < 0.05) could significantly decrease the level of uric acid in the model group which received PO 200 µM + XSS 10 µM, which demonstrate that such model could offer a new robust approach for high-throughput screening of food and drugs with uric acid-lowering activity.

High level of serum Cripto-1 in hepatocellular carcinoma, especially with hepatitis B virus infection.

BACKGROUND: Human Cripto-1 (CR-1), a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic protein family (EGF-CFC), is highly expressed in a variety of human cancers. We aimed to detect serum CR-1 level in liver diseases especially in hepatocellular carcinoma (HCC) patients. METHODS: Serum CR-1 level was Sandwich-type enzyme-linked immuno sorbent assay (ELISA) detected in 330 patients with liver diseases including HCC, cirrhosis, and chronic hepatitis and 50 volunteers without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection as control. RESULTS: The serum CR-1 level was significantly higher in HCC patients than volunteer controls and it was also significantly higher in HBV-related HCC than HCV-related HCC. In addition, serum CR-1 level was correlated with serum alpha-feto-protein (AFP) in HBV-related HCC patients. The serum CR-1 was also higher in cirrhosis and chronic hepatitis than volunteer controls. The serum CR-1 in HBV-related cirrhosis was higher than chronic hepatitis B, but there was no significant difference between HCV-related cirrhosis and chronic hepatitis C. CONCLUSIONS: Serum CR-1 was higher in HCC patients and might serve as a complementary biomarker to clinical diagnosis of HBV-related HCC. The high level of serum CR-1 in HBV-related liver disease might be partly attributed to HBV infection.

Caspase-dependent mitochondrial apoptotic pathway is involved in astilbin-mediated cytotoxicity in breast carcinoma cells.

Astilbin exhibits several pharmacological activities, including hypoglycemic, anti-oxidant and anti-inflammatory properties. The aim of the present study was to investigate the pro-apoptotic activities of astilbin on breast cancer in cells and mice. It was demonstrated that astilbin significantly reduced the cell viability, increased the cell apoptosis rate, suppressed the migration ability, caused the dissipation of the mitochondrial membrane potential and induced the overaccumulation of intracellular reactive oxygen species in MCF-7 and MDA-MB-231 cells after 12 or 24 h of exposure. Data obtained from western blotting suggested that astilbin suppressed the expression levels of B-cell lymphoma 2 (Bcl-2), while it increased the expression levels of cleaved caspase-3, -8 and -9, and Bcl-2-associated X protein in breast carcinoma cells. Furthermore, astilbin inhibited the growth of MCF-7-xenografted tumors in nude mice without influencing their bodyweights or organ (liver, spleen and kidney) functions. Additionally, astilbin enhanced the expression of pro-apoptotic proteins and suppressed the expression of anti-apoptotic proteins in tumor tissues. All these results revealed that astilbin exhibits pro-apoptotic properties in breast carcinoma cells via modulation of the caspase-dependent pathway, which highlights the feasibility of astilbin as a candidate agent for breast cancer treatment.

A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption.

A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.