Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma.

Sorafenib, which inhibits multiple kinases, is an effective frontline therapy for hepatocellular carcinoma (HCC). Ferroptosis is a form of iron-dependent programmed cell death regulated by lipid peroxidation, which can be induced by sorafenib treatment. Oncoprotein hepatitis B X-interacting protein (HBXIP) participates in multiple biological pro-tumor processes, including growth, metastasis, drug resistance, and metabolic reprogramming. However, the role of HBXIP in sorafenib-induced ferroptotic cell death remains unclear. In this study, we demonstrated that HBXIP prevents sorafenib-induced ferroptosis in HCC cells. Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced HCC cell death. Interestingly, suppression of HBXIP increased malondialdehyde (MDA) production and glutathione (GSH) depletion to promote sorafenib-mediated ferroptosis and cell death. Ferrostatin-1, a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by HBXIP silencing in HCC cells. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Functionally, activation of the HBXIP/SCD axis reduced the anticancer activity of sorafenib and suppressed ferroptotic cell death in vivo and in vitro. HBXIP/SCD axis-mediated ferroptosis can serve as a novel downstream effector of sorafenib. Our results provide new evidence for clinical decisions in HCC therapy.

Giant struma ovarii with pseudo-Meigs'syndrome and raised cancer antigen-125 levels: A case report.

BACKGROUND: Struma ovarii is a type of monodermal mature teratoma composed entirely or mainly of thyroid tissue, accounting for 1% to 3% of all ovarian teratomas and 0.3% to 1.0% of all ovarian tumors. Of which, struma ovarii with ascites and pleural effusion, called pseudo-Meigs'syndrome and raised cancer antigen-125 levels (CA 125) is even rarer. CASE SUMMARY: This paper reports the diagnosis and treatment of a patient of struma ovarii with pseudo-Meigs'syndrome, presenting with the clinical features of ovarian carcinoma: Complex pelvic mass, gross ascites, right pleural effusion and markedly elevated serum CA 125 levels. During the operation, a cystic-solid mass about 20 cm × 10 cm × 5 cm in the right adnexa and a solid mass with the size of 3 cm × 2 cm × 0.1 cm in the left ovary were observed. She underwent right adnexectomy and resection of the left ovarian mass and histopathology revealed a mature left-sided ovarian teratoma and struma ovarii of right adnexal mass. During 1-year follow-up, the patient recovered well, tumor markers and other indicators returned to normal. CONCLUSION: The diagnosis and treatment process of this case suggests that the clinical symptoms of struma ovarii with pseudo-Meigs'syndrome are lack specificity, which is easily misdiagnosed. Clinicians should improve the understanding of this disease, enhance the awareness of early screening, and improve the level of diagnosis and treatment.

Bilateral intracerebroventricular injection of streptozotocin induces AD-like behavioral impairments and neuropathological features in mice: Involved with the fundamental role of neuroinflammation.

OBJECTIVE: To establish an Alzheimer's disease (AD) mouse model, investigate the behavioral performance changes and intracerebral molecular changes induced by bilateral intracerebroventricular injection of streptozotocin (STZ/I.C.V), and explore the potential pathogenesis of AD. METHODS: An AD mouse model was established by STZ/I.C.V. The behavioral performance was observed via the open field test (OFT), novel object recognition test (NOR), and tail suspension test (TST). The mRNA and protein expressions of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in the hippocampus were measured via qPCR and Western blot. The expression of ß-amyloid 1-42 (Aß1-42), phosphorylated Tau protein (p-Tau (Ser396)), Tau5, ß-site amyloid precursor protein (APP) cleaving enzyme (BACE), insulin receptor substrate 1 (IRS1), brain-derived neurotrophic factor (BDNF), Copine6, synaptotagmin-1 (Syt-1), synapsin-1, phosphoinositol 3 kinase (PI3K), serine/threonine kinase (Akt), phosphorylated serine/threonine kinase (p-Akt (Ser473)), triggering receptor expressed on myeloid cells-1/2 (TREM1/2) were detected using Western blot, and the expression of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA1), Aß1-42, p-Tau(Ser396), Syt-1, BDNF were measured via immunofluorescence staining. RESULTS: STZ/I.C.V induced AD-like neuropsychiatric behaviors in mice, as indicated by the impairment of learning and memory, together with the reduced spontaneous movement and exploratory behavior. The expression of BACE, Aß1-42, p-Tau(Ser396), and TREM2 were significantly increased in the hippocampus of model mice, while the expression of IRS1, BDNF, Copine6, Syt-1, synapsin-1, PI3K, p-Akt(Ser473), and TREM1 were decreased as compared with that of the controls. Furthermore, the model mice presented a hyperactivation of astrocytes and microglia in the hippocampus, accompanied by the increased mRNA and protein expressions of IL-1ß, IL-6 and TNF-α. CONCLUSION: STZ/I.C.V is an effective way to induce AD mice model, with not only AD-like neuropsychiatric behaviors, but also typic AD-like neuropathological features including neurofibrillary tangles, deposit of ß-amyloid (Aß), neuroinflammation, and imbalanced synaptic plasticity.

BDNF rs6265 single-nucleotide polymorphism is involved in levodopa-induced dyskinesia in Parkinson's disease via its regulation of the cortical thickness of the left postcentral gyrus.

Background: Brain-derived neurotrophic factor (BDNF) gene rs6265 single-nucleotide polymorphism (SNP) is thought to be involved in neuroplasticity and influence the development of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This study aimed to determine how the BDNF rs6265 SNP regulates cortical thickness and to investigate the association between BDNF and the pathological mechanisms of LID in PD. Methods: This cross-sectional study recruited 75 patients with PD, including 37 patients with LID and 38 patients without LID, and 33 healthy controls. All the participants underwent T1-weighted magnetic resonance imaging (MRI) scans, clinical evaluations, and BDNF rs6265 genotyping. Two-way factorial analysis of covariance (ANCOVA) was used to explore the primary effects of disease status, rs6265 genotype, and their interactions on cortical thickness. Associations between cortical thickness in the regions of the brain affected by disease status-genotype interactions and clinical symptoms were detected using Spearman's rank-order correlation. Receiver operating characteristic (ROC) curve analysis was used to test cortical thickness measurements as an indicator of LID. Results: The main effects of disease status were observed in the right pars orbitalis (F=4.229, P=0.017), medial orbitofrontal cortex (F=3.639, P=0.030), and left banks superior temporal sulcus (F=3.172, P=0.046). The left pars orbitalis (F=4.541, P=0.036) and lingual gyrus (F=4.307, P=0.041) were thicker in carriers of the CC genotype than in carriers of the TC/TT genotype. Interaction between disease status and genotype showed that in the LID group, carriers of the CC genotype had a thicker left postcentral gyrus (mean difference =0.103, 95% confidence interval, 0.036 to 0.107, Bonferroni-corrected P<0.005) than did carriers of the TC/TT genotype, whereas no difference was found in the non-LID and healthy control (HC) groups. In carriers of the CC genotype, the cortical thickness of the left postcentral gyrus could identify whether patients with PD had LID, with an area under the receiver operating curve (AUC) of 0.757 (P=0.033, optimal cut-off =2.102). The cortical thickness of the left postcentral gyrus was also positively correlated with the Unified Dyskinesia Rating Scale (UDysRS) score in the LID-CC subgroup (r=0.825, P=0.001). Conclusions: The BDNF rs6265 SNP might be associated with dyskinesia symptoms in patients with PD and LID through its regulation of cortical thickness in the left postcentral gyrus.

Comparative analysis unveils the cadmium-induced reproductive toxicity on the testes of Pardosa pseudoannulata.

Cadmium (Cd) pollution is one of the most serious heavy metal pollutions in the world, which has been demonstrated to cause different toxicities to living organisms. Cd has been widely suggested to cause reproductive toxicity to vertebrates, yet its reproductive toxicity to invertebrates is not comprehensive. In this study, the wolf spider Pardosa pseudoannulata was used as a bioindicator to evaluate the male reproductive toxicity of invertebrates under Cd stress. Cd stress had no effect on the color, size and length of testis. However, Cd significantly increased the contents of catalase, glutathione peroxidase and malondialdehyde, the antioxidants in the testis of P. pseudoannulata. Then we analyzed the transcriptome of testis exposed to Cd, and identified a total of 4739 differentially expressed genes (DEGs) compared to control, with 2368 up-regulated and 2371 down-regulated. The enrichment analysis showed that Cd stress could affect spermatogenesis, sperm motility, post-embryonic development, oxidative phosphorylation and metabolism and synthesis of male reproductive components. At the same time, the protein-protein interaction network was constructed with the generated DEGs. Combined with the enrichment analysis of key modules, it revealed that Cd stress could further affect the metabolic process in testis. In general, the analysis of testicular damage and transcriptome under Cd stress can provide a novel insight into the reproductive toxicity of Cd on rice filed arthropods and offer a reference for the protection of rice filed spiders under Cd pollution.

Potential role of 25(OH)D insufficiency in the dysfunction of glycolipid metabolism and cognitive impairment in patients with T2DM.

Purpose: To investigate the changes of plasma 25(OH)D levels in type 2 diabetes mellitus (T2DM) patients and explore its role in the dysfunction of glucose and lipid metabolism and cognition. Methods: One hundred and thirty-two T2DM patients were enrolled and the demographic and clinical data were collected. The plasma concentration of 25(OH)D was detected and the patients were divided into two groups including a Vitamin D insufficient (VDI) group and a normal VD group according to the clinical diagnostic criterial of VDI with the plasma 25(OH)D level less than 29 ng/mL. The glycolipid metabolic and routine blood biochemical indices were detected, the plasma concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble myeloid soluble trigger receptor 1 (sTREM1) were measured. The cognitive function was assessed using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). The depressive symptomatology was assessed using the Center for Epidemiological Survey Depression Scale (CES-D). Sleep quality was assessed using the Pittsburgh sleep quality index (PSQI). Results: There were 70 T2DM patients with VDI (70/132, 53.03%) in this study. The plasma concentrations of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), IL-6, and sTREM1 were remarkably increased in T2DM patients with VDI as compared with that with the normal VD, accompanied with an elevated BRIEF-A scores. There was no significant difference between groups with regard to the indices of blood lipid, liver function, and scores in CES-D and PSQI. Moreover, results of Pearson correlation test showed that the plasma 25(OH)D levels were negatively correlated with HbA1c, FPG, PBG, CRP, IL-6, sTREM1, CES-D sum scores, and PSQI sum scores, but positively correlated with the plasma levels of Serum creatinine (Scr). Furthermore, result of Receiver Operating Characteristic (ROC) curve analysis showed a predictive role of VDI levels in discriminating T2DM patients with higher cognitive impairments, with the sensitivity and specificity being 62.12% and 62.12%, respectively. Conclusion: VDI is harmful for T2DM patients with a significant relation with the hyperglycosemia and cognitive dysfunction.

The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth.

Programmed death ligand-1 (PD-L1)/PD-1 checkpoint extensively serves as a central mediator of immunosuppression. A tumor-promoting role for abundant PD-L1 in several cancers is revealed. However, the importance of PD-L1 and how the PD-L1 expression is controlled in breast cancer remains obscure. Here, the mechanisms of controlling PD-L1 at the transcription and protein acetylation levels in promoting breast cancer growth are presented. Overexpressed PD-L1 accelerates breast cancer growth in vitro and in vivo. RNA-seq uncovers that PD-L1 can induce some target genes affecting many cellular processes, especially cancer development. In clinical breast cancer tissues and cells, PD-L1 and HBXIP are both increased, and their expressions are positively correlated. Mechanistic exploration identifies that HBXIP stimulates the transcription of PD-L1 through co-activating ETS2. Specifically, HBXIP induces PD-L1 acetylation at K270 site through interacting with acetyltransferase p300, leading to the stability of PD-L1 protein. Functionally, depletion of HBXIP attenuates PD-L1-accelerated breast tumor growth. Aspirin alleviates breast cancer via targeting PD-L1 and HBXIP. Collectively, the findings display new light into the mechanisms of controlling tumor PD-L1 and broaden the utility for PD-L1 as a target in breast cancer therapy.

[Prognostic Value of R-ISS Staging Combined with "Multiple-Hits" in Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic value of R-ISS staging combined with "Multiple-Hits" in patients with multiple myeloma (MM), and to detected the effect of different "Multiple- Hits" combinations to the prognosis of the patients. METHODS: The 220 MM patients treated in the hematology department of People's Hospital of Xinjiang Uygur Autonomous Region from April 2013 to October 2019 were enrolled and retrospective analyzed. All the patients were detected by FISH. The effects of R-ISS staging combined with "Multiple-Hits" and different "Multiple-Hits" combinations to the prognosis of the patients were compared. RESULTS: For the patients at R-ISS stage II and III, the median progression-free survival (PFS) time, overall survival (OS) time and duration of response (DOR) time in "Multiple-Hits" patients were all shorter than those without high-risk cytogenetic abnormality (HRCA) and those with only one type of HRCA (P<0.05), while the TTR (time to response) was significantly prolonged (P<0.05). For the prognosis of the patients among the three different "Multiple-Hits" combinations(1q21+ combined with del(17p), 1q21+ combined with t(14;16) and combined 1q21+ combined with t(4;14)), 1q21+ combined with del(17p) showed the worst prognosis. CONCLUSION: The patients with Different "Multiple-Hits" combinations shows different prognosis. The R-ISS staging combination with "Multiple-Hits" is more conducive to accurately judging the prognosis of MM patients.

Structural-fingerprinting of polysaccharides to discern Panax species by means of gas-liquid chromatography and mass spectrometry.

In this paper, a sequential gas-liquid chromatography and mass spectrometry route was proposed for characterization of polysaccharides in Panax ginseng (PG), P. notoginseng (PN), and P. quinquefolius (PQ). Due to the reflection of stepped structure parameters, the resulting integrative profiles were tentatively defined as structural-fingerprinting of polysaccharides (SFP) with monosaccharide compositional fingerprinting (MCF), Smith degradation and non-degradation fingerprinting (SDF and SNF), and oligosaccharide compositional fingerprinting (OCF). The MCF, OCF and SDF did not allow for visual discrimination of the three species due to the high interspecific similarity of PG and PQ, whereas SNF could intuitively distinguish PG, PN, and PQ by the presence or absence of Rha and the peak area ratio of Glc/Gal. Similarity analysis, heatmap analysis and principal component analysis were further performed to discern three Panax species based on SNF data sets. The linear →4)-Hexp-(1 â†’ structures were clearly identified as the common structural backbones in side chains or smooth regions of the main chain in PPG, PPN, and PPQ using HILIC-UHPLC-ESI--MS/MS for characterization of partial acid hydrolyzates. The experimental results displayed that the established SFP approach possesses high comprehensibility as well as satisfactory generalization capability for analysis of plant polysaccharides.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version).

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

A new standard reference film for oxygen gas transmission measurements.

A novel reference film was characterized to improve the oxygen gas transmission measurement accuracy of plastic materials for pharmaceutical packaging. The material processing, homogeneity, stability, jointly determined value and uncertainty evaluation were discussed. The film is the first reference film characterized by multiple laboratories using both manometric and coulometric methods. The oxygen transmission rate of the reference film was 20.53 with the expanded uncertainty of 1.36. The newly characterized reference film can be used in the calibration and self-calibration of oxygen transmission measurement equipment and analytical method verification to improve the measurement accuracy and achieve traceable data.

Gas chromatography-mass spectrometry-based trimethylsilyl-alditol derivatives for quantitation and fingerprint analysis of Anemarrhena asphodeloides Bunge polysaccharides.

Here we report a novel approach using gas chromatography mass spectrometry (GCMS)-based trimethylsilyl-alditol (TMSA) derivatives for simultaneous baseline separation and detection of 8 neutral saccharides and 2 uronic acids within 25 min. Using mild alkaline conditions to dissolve the sample in advance significantly increased both the detection sensitivity and sample stability of uronic acids because of occurrence of de-lactonization, whereas no obvious effects were observed for neutral saccharides. Sodium borohydride reduction of the carbonyl group of aldoses and the subsequent formation of TMSA derivatives simplifies GCMS chromatograms by producing a single peak for each derivatized sugar. The effects of both reaction temperatures and solvent ratios between HMDS and TMCS on formations of TMSA derivatives were also investigated. The established GCMS method was successfully applied for quantitation and fingerprint analysis of polysaccharides from the plant Anemarrhena asphodeloides Bunge. A comparative analysis of A. asphodeloides polysaccharides was further performed between TMSA and other four types of derivatizations. The results showed that GCMS analysis based on precolumn TMSA derivatization coupled with fingerprint analysis is a comprehensive and effective technique for qualitative and quantitative analysis of plant polysaccharides from traditional Chinese medicines.

Cartilage oligomeric matrix protein is a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway.

PURPOSE: Recent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer. METHODS: We investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA. We established COMP-knockout cells using the CRISPR/Cas9 system and COMP-overexpressing cells using lentiviral vectors to detect the effects of COMP on colon cancer cells using Cell Counting Kit-8 (CCK8), colony formation, apoptosis detection kit, and tumorigenesis assays in nude mice. RESULTS: The analysis of TCGA dataset and the results of the TMA suggested that COMP expression levels were significantly higher in cancer tissues than in adjacent normal tissues. Moreover, high COMP expression was correlated with the poor outcome of colon cancer patients. COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy. Colon cancer cells without COMP were defective with respect to the ability to proliferate, colony formation, the ability to resist 5-Fluorouracil-induced apoptosis and the growth of xenograft tumors in mice. Contrasting results were observed in COMP overexpressed cells. COMP promoted colon cancer cell proliferation partially through the activation of PI3K/ Akt/ mTOR/ p70S6K pathway. CONCLUSIONS: COMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.

Antiproliferative effect of double suicide gene delivery mediated by polyamidoamine dendrimers in human Tenon's capsule fibroblasts.

The aim of the present study was to investigate the therapeutic potential of a double suicide gene, thymidine kinase (TK) combined with cytosine deaminase (CD), mediated by generation of 5-polyamidoamine dendrimers (G5-PAMAM-D) on human Tenon's capsule fibroblasts (HTFs) as an anti-scarring agent. The pAcGFP1-Hyg-TK-CD plasmid was transfected into HTFs, and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect TK-CD expression. MTT cell proliferation assay was used to evaluate the cytotoxic effects of ganciclovir (GCV) and 5-flurocytosine (5-FC) on HTFs. The optimal concentration of GCV and 5-FC in TK-CD transfected HTFs (HTF-TK-CD) was selected by accessing the lowest and highest cytotoxicity caused, respectively. The morphological changes of transfected HTFs following treatment with GCV and 5-FC were observed by light and transmission electron microscopy. Results demonstrated that the double suicide gene TK-CD mediated by the G5-PAMAM-D delivery system was successfully expressed in HTFs as determined by RT-PCR. A concentration of 3 µg/ml GCV and 200 µg/ml 5-FC was identified as optimal for these prodrugs. The growth rate and number of HTF-TK-CD cells decreased following treatment with GCV and 5-FC as revealed by light microscopy. Additionally, the prodrugs GCV and 5-FC not only demonstrated toxicity on transfected HTFs but also exerted a 'bystander effect'. The present study illustrated that the double suicide gene TK-CD delivery mediated by G5-PAMAM-D was effective in reducing HTF proliferation and inducing cell apoptosis. Furthermore, TK-CD delivery mediated by G5-PAMAM-D may be used as an anti-scarring agent and provide a therapeutic potential for patients requiring glaucoma filtration surgery.

Integrative hepatoprotective efficacy comparison of raw and vinegar-baked Radix Bupleuri using nuclear magnetic resonance-based metabolomics.

Radix Bupleuri (RB), with a Chinese name Chaihu, is one of the most popular Traditional Chinese herbal drug. It can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in Traditional Chinese Medicine (TCM) for liver diseases treatment. In the present study, nuclear magnetic resonance-based metabolomic approach was used to compare the liver protective effect of RB and two types of VBRBs, which were prepared by two kinds of vinegar. The contents of 14 metabolites in the liver of carbon tetrachloride (CCl4) treated mice were significantly altered in comparison with control group, and VBRB prepared by Shanxi vinegar showed best effect as revealed by the amount and regulatory degree of the perturbed metabolites. The metabolism pathways analysis showed that the liver protective effect was related with the energy metabolism, lipid metabolism, ketone body metabolism, glutathione metabolism, amino acids metabolism and nucleotide synthesis. The results presented here showed that metabolomic approach made it possible to disclose the subtle biological difference between two types of VBRB, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs.

SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer.

Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.

Overexpression of LARP1 predicts poor prognosis of colorectal cancer and is expected to be a potential therapeutic target.

This study investigated the significance of La-related protein 1 (LARP1) in the development and progression of colorectal cancer (CRC). Quantitative real-time polymerase chain reaction and Western blot analyses were carried out to determine the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent normal mucosa. The expression of LARP1 was upregulated in CRC. Immunohistochemical analysis using tissue microarray was performed. A positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed using the Spearman's correlation coefficient test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001), American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank (P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed that LARP1 was an independent prognostic factor for overall survival (OS; hazard rate (HR) = 0.244; 95 % confidence interval (CI), 0.078-0.769; P = 0.016) and disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086-0.917; P = 0.035) in CRC patients. LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.

Screening adulteration of polypropylene bottles with postconsumer recycled plastics for oral drug package by near-infrared spectroscopy.

Adulteration of pharmaceutical packaging containers with postconsumer recycled plastic materials was considerably difficult to identify due to the similar chemical compositions of virgin and recycled plastics. In the present study, near-infrared (NIR) spectroscopy coupled with conformity test was proposed to screen the adulteration of pharmaceutical packaging containers. Two kinds of representative screening models were investigated on polypropylene (PP) bottles for oral drug package. The reliability of the screening models was validated through studying the identification reliability, specificity, and robustness of the methods. The minimum spiking level of two modeled adulterants at the proportion of 20% could be detected, and the unqualified sample from a domestic manufacturer was rejected by this developed method. This strategy represents a rapid and promising analytical method for screening the adulteration of pharmaceutical plastic packaging containers with postconsumer recycled plastics.

Isolation and difference in anti-Staphylococcus aureus bioactivity of curvularin derivates from fungus Eupenicillium sp.

With the anti-microbial and anti-tumor composite screening model, bioassay-guided fractionation led to the isolation of two structurally related bioactive compounds, curvularin and alphabeta-dehydrocurvularin, from ethyl acetate extract of Eupenicillium sp. associated with marine sponge Axinella sp. Further study on the structure-activity relationship demonstrated that both compounds exhibited differences in bioactive profiles which are highly associated with their minor structural differences. Both curvularin and alphabeta-dehydrocurvularin have similar level of anti-fungal and anti-tumorous activity, while alphabeta-dehydrocurvularin is active against Staphylococcus aureus with a minimal inhibitory concentration of 375 microg/ml but curvularin does not. No detectable activity against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa exists for both compounds. It is suggested that the partial planar backbone structure, due to the conjugation of pi electrons in the presence of a 3,4-double bond and the carbonyl group at position C-2 in alphabeta-dehydrocurvularin, acts as a key factor for the inhibition of S. aureus, a Gram-positive low G + C bacteria that are often the hospital-acquired and/or community-acquired pathogen.