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Hepatocellular carcinoma (HCC) is characterized by uncontrolled proliferation and the deregulation of apoptotic signaling, although its molecular pathogenesis is not fully characterized. The ability to inhibit excessive proliferation and induce the apoptosis of cancer cells are crucial characteristics of anticancer drugs. Pien Tze Huang (PZH) is a widely used traditional Chinese medicine for the treatment of various types of cancer, and has exhibited promising therapeutic effects in clinical trials of HCC. However, the underlying mechanisms for its action are unclear. In the present study, the aim was to explore the effect of PZH on the proliferation and apoptosis of the BEL‑7402 HCC cell line, and the associated mechanisms. PZH treatment significantly inhibited BEL‑7402 cell viability, confluence and clonogenicity, inducing cell cycle arrest and promoting apoptosis. In addition, PZH treatment suppressed the expression of the pro‑proliferative genes cyclin D1 and cyclin‑dependent kinase 4, and decreased the expression of the anti‑apoptotic gene Bcl‑2. PZH treatment also upregulated the expression of a key microRNA (miR), miR‑16. The study demonstrated that PZH can effectively inhibit cancer cell proliferation and induce apoptosis in BEL‑7402 HCC cells via the upregulation of the tumor suppressor miR‑16. [ABSTRACT FROM AUTHOR]

The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0.05). PZH inhibited cell survival, reduced the proportion of cells in S-phase, and suppressed the expression of pro-proliferative proteins cyclin D1 and cyclin-dependent kinase 4. In addition, PZH treatment induced nuclear condensation and fragmentation, activated caspase-9 and -3 and increased the pro-apoptotic Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio. Furthermore, PZH treatment upregulated the expression of microRNA-22 (miR-22) and downregulated the expression of c-Myc (a target gene of miR-22). In conclusion, the findings from the present study suggest that PZH can overcome chemo-resistance in cancer cells, likely through increasing miR-22 expression, and by reversing the imbalance between levels of proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents, including 5-fluorouracil (5-FU), frequently cause intestinal mucositis as a side effect, leading to life quality reduction in colorectal cancer (CRC) patients and interruption of CRC treatment. Traditional Chinese medicines (TCMs) have recently received attention due to their relatively few adverse effects. Pien Tze Huang (PZH), a well-known TCM formulation first documented to have been prescribed >450 years ago, has been demonstrated to be clinically effective in treating various types of cancer including CRC. Although previous studies by our group reported that PZH possesses a variety of anti-cancer activities via multiple mechanisms, it has remained elusive whether it is able to reduce intestinal mucositis induced by 5-FU. The present study evaluated the effect of PZH on 5-FU-induced intestinal mucositis in CT-26 tumor-bearing xenograft mice and investigated the possible molecular mechanism. The results indicated that administration of PZH effectively alleviated the severity of 5-FU-induced diarrhea and morphological intestinal damages, but had no significant effect on body weight loss. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay revealed that PZH treatment significantly inhibited cell apoptosis in the intestinal crypt. Furthermore, immunohistochemical staining showed that PZH treatment reduced the protein expression of pro-apoptotic B-cell lymphoma 2 (Bcl-2)-associated X protein but enhanced that of anti-apoptotic Bcl-2 in the intestinal crypt. Taken together, the results of the present study suggested that PZH effectively attenuates 5-FU-induced intestinal mucositis, which is in part associated with its inhibitory effect on cell apoptosis in the intestinal crypt. [ABSTRACT FROM AUTHOR]

The Magnoliaceae shows strong phylogenetic niche conservatism, in which temporal petal closure has been extensively reported. However, it is yet elusive whether temporal petal closure is an idle floral character inherited from their ancestors or an adaptive trait to their habitats. Here, we monitored the process of temporal floral closure and re-opening in a thermogenic plant, Magnolia denudata (Magnoliaceae). Furthermore, we artificially interrupted temporal petal closure and investigated its effects on development of female and male gametophytes. Intriguingly, we found considerable anatomical changes in the anthers shortly after temporal closure of petals: disintegration of tapeta, crack of anther walls, and release of matured pollens. In comparison with normal flowers, artificially interrupted flowers (no petal closure) showed delayed anther development and slower pollen germination on stigmas, while little difference in embryo morphology was observed during the early stage of embryo development. Moreover, seed set and quality were significantly decreased when petal closure was prevented. In addition, we found pollination accelerated floral closure in M. denudata. Taken together, temporal floral closure benefits reproduction of M. denudata in early spring by promoting anther development and pollen function, which suggests that it is an adaptive floral trait to its specific habitat. [ABSTRACT FROM AUTHOR]

In the framework of a b-metric space, by using the compatible and weak compatible conditions of self-mapping pair, we discussed the existence and uniqueness of the common fixed point for a class of ϕ-type contraction mapping, some new common fixed point theorems are obtained. In the end of the paper, we give some illustrative examples in support of our new results. The results presented in this paper extend and improve some well-known comparable results in the existing literature. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a widespread health concern, and there is currently insufficient understanding regarding its pathogenesis and treatment. The present study aimed to explore the effects of Artemisia capillaris formula (ACF) on high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation, by micro (mi)RNA regulation. A total of 72 Sprague-Dawley rats were divided into six groups (n=12/group). One group was designated as the control group and fed a normal diet, and the remaining five groups were allowed ad libitum access to a high-fat diet for eight weeks, in order to establish an NAFLD rat model. The rats were subsequently administered polyene phosphatidylcholine (PP; 0.076 g/kg body weight/day), low dose of ACF (0.462 g/kg body weight/day), middle dose of ACF (0.924 g/kg body weight/day) or high dose of ACF (1.848 g/kg body weight/day) intragastrically for four weeks. HepG2 human hepatocellular carcinoma cells were treated with oleic acid and palm acid, followed by treatment with various concentrations of ACF. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and steatotic HepG2 human liver carcinoma cell TC and TG levels were measured. ACF and PP treatments attenuated high-fat diet-induced hepatic steatosis and fatty acid-induced intracellular lipid accumulation. A modified high-fat diet significantly increased ALT, AST, TG, TC, LDL-C levels and decreased HDL-C levels. Treatment with ACF and PP abrogated the increase in liver enzymes and TG, TC and LDL-C levels, but did not influence HDL-C levels in a high-fat diet induced rat model of steotosis. Steatotic HepG2 cells exhibited significantly increased levels of both TG and TC. Treatment with ACF significantly decreased TC and TG levels in vivo, and ACF and PP treatment decreased the expression levels of fatty acid synthase (FASN) and increased miR-122 in vivo and in vitro. In conclusion, these results suggested that ACF may inhibit hepatic steatosis via miR-122-induced downregulation of FASN in vivo and in vitro. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to prove some new coupled common fixed point theorems for mappings defined on a set equipped with two S-metrics. We also provide illustrative examples in support of our new results. Meantime, we give an existence and uniqueness theorem of solution for a class of nonlinear integral equations by using the obtained result. [ABSTRACT FROM AUTHOR]

In the past few years, genome-wide association study (GWAS) has made great successes in identifying genetic susceptibility loci underlying many complex diseases and traits. The findings provide important genetic insights into understanding pathogenesis of diseases. In this paper, we present an overview of widely used approaches and strategies for analysis of GWAS, offered a general consideration to deal with GWAS data. The issues regarding data quality control, population structure, association analysis, multiple comparison and visual presentation of GWAS results are discussed; other advanced topics including the issue of missing heritability, meta-analysis, setbased association analysis, copy number variation analysis and GWAS cohort analysis are also briefly introduced. [ABSTRACT FROM AUTHOR]

The present study investigated whether Qianliening capsules (QC) affected the apoptosis of benign prostatic hyperplastia epithelial (BPH-1) cells by regulating the extracellular matrix (ECM). The levels of fibronectin (FN) and collagen IV were determined in the culture medium of BPH-1 cells maintained in normal medium and of BPH-1 cells maintained in an environment rich in FN and collagen IV using an enzyme-linked immunosorbent assay. Reverse transcription quantitative polymerase chain reaction and western blot analysis were performed to determine the mRNA and protein expression levels of FN, collagen IV, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cyclin D1, respectively. The cell morphology and viability were determined using light microscopy and an MTT assay and cell apoptosis was detected by annexin V staining. The results demonstrated that FN and collagen IV affected the apoptotic response of the BPH-1 cells, QC treatment significantly reduced the levels of FN and collagen IV secreted by the cells into the culture medium (P<0.01), inhibited the mRNA and protein expression levels of FN, collagen IV, Bcl-2 and cyclin D1 and promoted the mRNA and protein expression of Bax. Therefore, one of the mechanisms underlying the anti-BPH action of QC involves promoting apoptosis by regulating the expression of the extracellular matrix. [ABSTRACT FROM AUTHOR]

Background: The correlation between overall survival (OS) and progression-free survival (PFS) has been evaluated in patients with metastatic or advanced gastric cancer who have received first-line and/or second-line chemotherapy. However, no corresponding analysis has been done for patients who have undergone third-line or later-line chemotherapy. Methods: A total of 303 patients from the Phase II/III studies of apatinib were pooled (the Phase II study as a training data set, the Phase III study as a testing data set). Landmark analyses of PFS at 2 months from randomization were performed to minimize lead time bias. The Cox proportional hazard model was used to test for the significance effect of PFS rate at 2 months in predicting OS. Additionally, the PFS/OS correlations were evaluated by the normal induced copula (National Institute for Health and Care Excellence) estimation model. Results: The median OS was 3.37 months (95% confidence interval 2.63-3.80) in patients who experienced progression at 2 months and 5.67 months in patients who did not (95% confidence interval 4.83-6.67; P<0.0001). Compared with patients who did not progress at 2 months, the adjusted hazard ratio for death was 3.39 (95% confidence interval 1.79-6.41; P,0.0001) for patients who experienced progression at 2 months. Moreover, the correlation of PFS/OS was 0.84 (95% confidence interval 0.74-0.90). Similar results were found in the testing data set. Conclusion: These results indicate that PFS correlates strongly with OS, suggesting PFS may be a useful early endpoint for patients with advanced gastric cancer who have undergone thirdline or later-line chemotherapy. These observations require prospective validation. [ABSTRACT FROM AUTHOR]

Background The aim of present study is to investigate the hypocholesterolemic effects of the oat components other than the β-glucan in rats fed with a hypercholesterolemic diet. Methods Four-week-old male Wister rats were divided into 6 groups of 7 rats each with similar mean body weights and serum cholesterol concentrations. Rats were fed with the experimental diets containing 10% oats flour for 30 days. Food intake was recorded and monitored everyday to ensure the similar contents of protein, starch, lipid and cellulose in all groups. The lipids levels in serum, liver, and faeces were determined. Results The plasma total cholesterol concentrations in different oat groups were significantly reduced compared with the control group, and the effects were different among oat groups. The decrease extent of plasma total cholesterol and low-density lipoprotein-cholesterol concentrations increased with the increase of the proteins and lipids contents. Moreover, liver total cholesterol and cholesterol ester contents were markedly decreased. The fecal bile acids concentrations in the oat groups were significantly increased. Oat proteins had lower Lysine/Arginin (0.59 ~ 0.66) and Methionin/Glycine (0.27 ~ 0.35) ratio than casein (Lysine/Arginin, 2.33; Methionin/Glycine, 1.51). Oat lipids contained higher contents of total Vitamin E and plant sterols than that in soybean oil. Conclusion These results indicated that dietary oat improved hypercholesterolemia by increasing the excretions of fecal bile acids, and this improvement was not only related to β-glucan, but also attributed to the lipids and proteins. Oat proteins decreased serum total cholesterol and low-density lipoprotein-cholesterol contents due to their low Lysine/Arginin and Methionin/Glycine ratio. The co-existence of oleic acid, linoleic, vitamin E, or plant sterols accounted for the hypocholesterolemic properties of oat lipids. [ABSTRACT FROM AUTHOR]

Background: Estimating the disease prevalence and test accuracy (sensitivity and specificity) for two dependent screening tests when the status of individuals who are negative on both tests is unverified represents a considerable challenge, as the disease rates for individuals negative on both tests are not identifiable without additional assumptions. Methods: This article presents a unified framework for handling this non-identifiability problem using two-step hierarchical informative prior on the sensitivities by two-stage Bayesian modeling with the characterized by joint testing strategies based on the inherent attribute of screening/diagnostic tests. We assign a diffuse and less risky two-step hierarchical informative uniform prior to the sensitivities while assigning a uniform (0,1) prior distribution to the specificities and prevalence. Strategies for model evaluation, general global evaluations, and individual cell checking are presented. Simulations are conducted under various scenarios to evaluate the performance of the proposed method. Applications to real data are also presented to illustrate the potential impact and benefit of the proposed method. Results: Our results indicate that when the priors of sensitivities are assigned as appropriate two-step hierarchical informative priors, or even in the absence of the priors for the specificities and prevalence, the parameters involved in this study can still be estimated well. The advantages and limitations of this method in solving such problems are discussed and compared with other two-stage methods. Conclusions: We developed a two-stage Bayesian method for two dependent dichotomous screening tests with unverified individuals who are negative on both tests, and addressed the ad hoc model evaluation and checking procedures. The method can be understood easily and used conveniently by non-statisticians. [ABSTRACT FROM AUTHOR]

Spica Prunellae has long been used as a significant component in numerous traditional Chinese medicine (TCM) formulas to clinically treat cancers. Previously, Spica Prunellae was shown to promote cancer cell apoptosis and inhibit angiogenesis in vivo and in vitro. To further elucidate the precise mechanism of its tumoricidal activity, the effect of the ethanol extract of Spica Prunellae (EESP) on the proliferation of human colon carcinoma HT-29 cells was elucidated and the underlying molecular mechanisms were investigated. The proliferation of HT-29 cells was evaluated using 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation analyses. The cell cycle was determined using fluorescence-activated cell sorting (FACS) with propidium iodide (PI) staining. The mRNA and protein expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1 was examined using RT-PCR and western blotting, respectively. EESP was observed to inhibit HT-29 viability and survival in a dose- and time-dependent manner. Furthermore, EESP treatment blocked Gj/S cell cycle progression and reduced the expression of pro-proliferative cyclin D1 and CDK4 at the transcriptional and translational levels. Altogether, these data suggest that the inhibition of cell prolif- eration via Gj/S cell cycle arrest may be one of the mechanisms through which Spica Prunellae treats cancer. [ABSTRACT FROM AUTHOR]

This research investigated the development of critical thinking of middle school chemistry teachers in Shaanxi province of China. In-service and pre-service teachers' critical thinking are examined in order to provide evidence for establishing teachers' standard. The sample in this study consisted of 69 in-service and 61 pre-service chemistry teachers. The California Critical Thinking Disposition Inventory (CCTDI) and California Critical Thinking Skills Test (CCTST) are used to assess the teachers' critical thinking. The results indicates that the teacher' dispositions toward critical thinking are at an average level while their scores of critical thinking skills are very low. This research also shows there are statistically significant differences between in-service and pre-service teachers in their critical thinking skills, but no significant difference in their critical thinking dispositions. Additionally, both CCTST and CCTDI mean scores reflect that the pre-service chemistry teachers performed better than the in-service teachers toward critical thinking. [ABSTRACT FROM AUTHOR]

Purpose This network meta-analysis (NMA) was conducted to compare the efficacy of immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC) patients with liver metastases. Materials and Methods English literature was retrieved from the PubMed, American Society of Clinical Oncology, and European Society for Medical Oncology databases from January 2015 to January 2021. We pooled the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) using an NMA and ranked treatments by the surface under the cumulative ranking curve. Publication bias was evaluated by Begg’s and Egger’s tests. STATA 15.0 was used for the sensitivity analysis, and the remaining statistical analyses were performed using R 4.0.2. Results Nine eligible phase III randomized controlled trials were included, including 1,141 patients with liver metastases. Pembrolizumab+chemotherapy ranked highest, followed by atezolizumab+bevacizumab+chemotherapy and nivolumab. However, no significant difference in OS rates was observed across these three treatments (HR, 0.98; 95% confidence interval [CI], 0.43 to 2.22 for pembrolizumab+chemotherapy vs. atezolizumab+bevacizumab+chemotherapy; HR, 0.91; 95% CI, 0.52 to 1.57 for pembrolizumab+chemotherapy vs. nivolumab). Regarding the PFS rate, atezolizumab+bevacizumab+chemotherapy and pembrolizumab+ chemotherapy ranked highest and no significant difference was observed between them (HR, 0.79; 95% CI, 0.36 to 1.70 for atezolizumab+bevacizumab+chemotherapy vs. pembrolizumab+chemotherapy). Conclusion Pembrolizumab+chemotherapy, atezolizumab+bevacizumab+chemotherapy, and nivolumab were superior to other treatments in NSCLC patients with liver metastases. These new findings may help clinicians better select therapeutic strategies for NSCLC patients with liver metastases. [ABSTRACT FROM AUTHOR]

The aim of the present study is to investigate the effects of dietary wheat bran arabinoxylans (AXs) on cholesterol metabolism in hypercholesterolemic hamsters. The hamsters were divided into 3 groups and fed the experimental diets containing AXs or oat ß-glucan at a dose of 5g/kg for 30 days. As the results, the AXs lowered plasma total cholesterol and LDL-cholesterol concentrations, and increased excretions of total lipids, cholesterol and bile acids, as well as oat ß-glucan. The AXs reduced the activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase, and increased the activity of cholesterol 7-a hydroxylase (CYP7A1) in liver. Moreover, the AXs increased propionate and the total short-chain fatty acids (SCFAs) concentrations. These results indicated that dietary AXs reduced the plasma total cholesterol and LDL-cholesterol concentrations by promoting the excretion of fecal lipids, regulating the activities of HMG-CoA reductase and CYP7A1, and increasing colonic SCFAs in hamsters. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used as a folk remedy for cancer. To elucidate the mode of action of PZH against cancer, in the present study we used a 5-FU resistant human colorectal carcinoma cell line (HCT-8/5-FU) to evaluate the effects of PZH on multidrug resistance (MDR) and epithelial-mesenchymal transition (EMT) as well as the activation of TGF-β pathway. We found that PZH dose-dependently inhibited the viability of HCT-8/5-FU cells which were insensitive to treatment of 5-FU and ADM, demonstrating the ability of PZH to overcome chemoresistance. Furthermore, PZH increased the intercellular accumulation of Rhodamine-123 and downregulated the expression of ABCG2 in HCT-8/5-FU cells. In addition, drug resistance induced the process of EMT in HCT-8 cells as evidenced by EMT-related morphological changes and alteration in the expression of EMT-regulatory factors, which however was neutralized by PZH treatment. Moreover, PZH inhibited MDR/EMT-enhanced migration and invasion capabilities of HCT-8 cells in a dose-dependent manner and suppressed MDR-induced activation of TGF-β signaling in HCT-8/5-FU cells. Taken together, our study suggests that PZH can effectively overcome MDR and inhibit EMT in human colorectal carcinoma cells via suppression of the TGF-β pathway. [ABSTRACT FROM AUTHOR]