Microbiological Mechanisms of Collaborative Remediation of Cadmium-Contaminated Soil with Bacillus cereus and Lawn Plants.

Severe cadmium contamination poses a serious threat to food security and human health. Plant-microbial combined remediation represents a potential technique for reducing heavy metals in soil. The main objective of this study is to explore the remediation mechanism of cadmium-contaminated soil using a combined approach of lawn plants and microbes. The target bacterium Bacillus cereus was selected from cadmium-contaminated soil in mining areas, and two lawn plants (Festuca arundinacea A'rid III' and Poa pratensis M'idnight II') were chosen as the target plants. We investigated the remediation effect of different concentrations of bacterial solution on cadmium-contaminated soil using two lawn plants through pot experiments, as well as the impact on the soil microbial community structure. The results demonstrate that Bacillus cereus promotes plant growth, and the combined action of lawn plants and Bacillus cereus improves soil quality, enhancing the bioavailability of cadmium in the soil. At a bacterial suspension concentration of 105 CFU/mL, the optimal remediation treatment was observed. The removal efficiency of cadmium in the soil under Festuca arundinacea and Poa pratensis treatments reached 33.69% and 33.33%, respectively. Additionally, the content of bioavailable cadmium in the rhizosphere soil increased by up to 13.43% and 26.54%, respectively. Bacillus cereus increased the bacterial diversity in the non-rhizosphere soil of both lawn plants but reduced it in the rhizosphere soil. Additionally, the relative abundance of Actinobacteriota and Firmicutes, which have potential for heavy metal remediation, increased after the application of the bacterial solution. This study demonstrates that Bacillus cereus can enhance the potential of lawn plants to remediate cadmium-contaminated soil and reshape the microbial communities in both rhizosphere and non-rhizosphere soils.

Clinical and economic comparison of laparoscopic versus open hepatectomy for primary hepatolithiasis: a propensity score-matched cohort study.

BACKGROUND: It is unclear whether laparoscopic hepatectomy (LH) for hepatolithiasis confers better clinical benefit and lower hospital costs than open hepatectomy (OH). This study aim to evaluate the clinical and economic value of LH versus OH. METHODS: Patients undergoing OH or LH for primary hepatolithiasis at Yijishan Hospital of Wannan Medical College between 2015 and 2022 were divided into OH group and LH group. Propensity score matching (PSM) was used to balance the baseline data. Deviation-based cost modelling and weighted average median cost (WAMC) were used to assess and compare the economic value. RESULTS: A total of 853 patients were identified. After exclusions, 403 patients with primary hepatolithiasis underwent anatomical hepatectomy (OH n=143; LH n=260). PSM resulted in 2 groups of 100 patients each. Although LH required a longer median operation duration compared with OH (285.0 versus 240.0 min, respectively, P<0.001), LH patients had fewer wound infections, fewer pre-discharge overall complications (26 versus 43%, respectively, P=0.009), and shorter median postoperative hospital stays (8.0 versus 12.0 days, respectively, P<0.001). No differences were found in blood loss, major complications, stone clearance, and mortality between the two matched groups. However, the median overall hospital cost of LH was significantly higher than that of OH (CNY¥52,196.1 versus 45,349.5, respectively, P=0.007). Although LH patients had shorter median postoperative hospital stays and fewer complications than OH patients, the WAMC was still higher for the LH group than for the OH group with an increase of CNY¥9,755.2 per patient undergoing LH. CONCLUSION: The overall clinical benefit of LH for hepatolithiasis is comparable or even superior to that of OH, but with an economic disadvantage. There is a need to effectively reduce the hospital costs of LH and the gap between costs and diagnosis-related group reimbursement to promote its adoption.

Preoperative plasma fibrinogen and C-reactive protein/albumin ratio as prognostic biomarkers for pancreatic carcinoma.

Objective: Pancreatic carcinoma is characterised by high aggressiveness and a bleak prognosis; optimising related treatment decisions depends on the availability of reliable prognostic markers. This study was designed to compare various blood biomarkers, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin (Alb), plasma fibrinogen (PF), and CRP/Alb in patients with pancreatic carcinoma. Methods: Our study retrospectively reviewed 250 patients with pancreatic carcinoma diagnosed between July 2007 and December 2018. The Cutoff Finder application was used to calculate the optimal values of CRP/Alb and PF. The Chi-square test or Fisher's exact test was used to analyse the correlation of CRP/Alb and PF with other clinicopathological factors. Conducting univariate and multivariate analyses allowed further survival analysis of these prognostic factors. Results: Multivariate analysis revealed that, in a cohort of 232 patients with pancreatic ductal adenocarcinoma (PDAC), the PF level exhibited statistical significance for overall survival (hazard ratio (HR) = 0.464; p = 0.023); however, this correlation was not found in the entire group of 250 patients with pancreatic carcinoma. Contrastingly, the CRP/Alb ratio was demonstrated statistical significance in both the entire pancreatic carcinoma cohort (HR = 0.471; p = 0.026) and the PDAC subgroup (HR = 0.484; p = 0.034). CRP/Alb and PF demonstrated a positive association (r=0.489, p<0.001) as indicated by Spearman's rank correlation analysis. Additionally, in 232 PDAC patients, the combination of the CRP/Alb ratio and PF had synergistic effects on prognosis when compared with either the CRP/Alb ratio or the PF concentration alone. Conclusion: PF concentration is a convenient, rapid, and noninvasive biomarker, and its combination with the CRP/Alb ratio could significantly enhance the accuracy of prognosis prediction in pancreatic carcinoma patients, especially those with the most common histological subtype of PDAC.

Comprehensive profiling of cell subsets of gastric cancer and liver metastasis based on single cell RNA-sequencing analysis.

Background: Liver metastasis (Li) is one of the most common distant metastatic sites for gastric cancer. A deeper understanding of its mechanism of action from a bioinformatics perspective may provide new insights. Therefore, the aim of this study was to use single cell RNA sequencing (scRNA-seq) to evaluate cell subtypes and understand the molecular mechanism of gastric cancer Li. Methods: The scRNA-seq data GSE163558 of gastric cancer and Li were downloaded from Gene Expression Omnibus (GEO). Single cell data were analyzed by various R packages such as Seurat, CellChat, gene set variation analysis (GSVA), monocle, gene set enrichment analysis (GSEA), and survival analysis and the results were plotted by ggplot2, R4.1.1. Protein expression was confirmed by immunohistochemistry in an additional patient cohort. Results: The genes APOD, CXCL5, and JUN are involved in epithelial cell metastasis. The infiltration of cytotoxic CD8 T cells was more frequent in gastric primary tumors (PTs) than in Lis. IL7R high natural killer (NK) cells that had high TXNIP and RIPOR2 expression were located at the site of Li and corresponded to a favorable prognosis. NK cells with high TNFAIP3 expression were located at the PT site and corresponded to a poor prognosis. Furthermore, the gene expression of myeloid cells was different depending on their localization in the PT site or Li. MHC-I signaling pathway was found to be activated in the PT compared to MHC-II at the site of Li, as revealed by cell-cell interaction, and HLA-E-CD94/NKG2A of NK cells was only activated in the PT and not in the Li. Conclusions: The present study revealed the difference between Li and gastric PT by scRNA-seq, demonstrating the impact of partial gene expression on patient prognosis. Our study provides new insights into gastric cancer and Li.

Ultrasound-assisted extraction of polyphenols from pine needles (Pinus elliottii): Comprehensive insights from RSM optimization, antioxidant activity, UHPLC-Q-Exactive Orbitrap MS/MS analysis and kinetic model.

Extracting polyphenolic bioactive compounds from Pinus elliottii needles, a forestry residue, promises economic and environmental benefits, however, relevant experimental data are lacking. Herein, a comprehensive investigation of the polyphenolic composition of pine needles (PNs) was carried out. Ultrasound-Assisted Extraction (UAE) was applied to extract the polyphenolic compounds of pine needles. The optimal conditions of extracts were determined by Response Surface Methodology (RSM). The maximum total phenolic content (TPC) of 40.37 mg GAE/g PNs was achieved with solid-liquid ratio of 1:20, 60 % ethanol, and 350 W for 25 min at 45 °C. Polyphenolic extracts showed antioxidant activity in scavenging free radicals and reducing power (DPPH, IC50 41.05 µg/mL; FRAP 1.09 mM Fe2+/g PNs; ABTS, IC50 214.07 µg/mL). Furthermore, the second-order kinetic model was also constructed to describe the mechanism of the UAE process, with the extraction activation energy estimated at 12.26 kJ/mol. In addition, 37 compounds in PNs were first identified by UHPLC-Q-Exactive Orbitrap MS/MS, including flavonoids and phenolic acids. The results suggest that Ultrasound-Assisted is an effective method for the extraction of natural polyphenolic compounds from pine needles and this study could serve as a foundation for utilizing phenolics derived from PNs in the food and pharmaceutical industries.

Interpreting the chemical changes and therapeutic effect of Coptidis Rhizoma against ulcerative colitis before and after processing based on mathematical statistics and network pharmacology.

INTRODUCTION: Coptidis Rhizoma (CR) is one of the most frequently used herbs to treat ulcerative colitis (UC) and is often processed before usage. However, the composition changes and therapeutic effects of CR before and after processing in the treatment of UC are still unclear. OBJECTIVE: The purpose of the study is to explore the chemical components and therapeutic effects of crude and processed CR. MATERIAL AND METHODS: CR was processed according to the 2020 version of the Chinese Pharmacopoeia. The liquid chromatography-mass spectrometry (LC-MS) and multivariate statistical analysis were used to screen the different compounds before and after processing. The network pharmacological prediction was carried out. The mechanism and therapeutic effects between crude and processed CR were verified by using dextran sulphate sodium-induced UC mice assay. RESULTS: Ten compounds distinguish crude and processed CR based on multivariate statistical analysis. Network pharmacology predicts that the 10 compounds mainly play a role through TNF-α and IL-6 targets and PI3K/Akt and HIF-1 signalling pathways, and these results are verified by molecular biology experiments. For IL-6, IL-10 and TNF-α inflammatory factors, CR is not effective, while CR stir-fried with Evodiae Fructus (CRFE) and ginger juice (CRGJ) are. For PI3K/p-Akt, Cleaved caspase3, NF- κBp65 and HIF-1α signalling pathways, CR has therapeutic effects, while CRFE and CRGJ are significant. CONCLUSION: Overall, CRFE and CRGJ show better effects in treating UC. The chemical changes of processing and the efficacy of processed CR are correlated, which provides a scientific basis for the clinical use of crude and processed CR.

Comparison of the effects of ampulla-guided realignment and conventional gallbladder triangle anatomy in difficult laparoscopic cholecystectomy.

OBJECTIVE: To compare the effects of ampulla-guided realignment and conventional gallbladder triangle anatomy in difficult laparoscopic cholecystectomy (DLC). METHODS: From June 2021 to August 2022, data from 100 patients undergoing DLC at Nanjing Hospital of Traditional Chinese Medicine were analyzed retrospectively. Patients were divided into two groups: the experimental group (LC with the ampulla-guided realignment) and the control group (conventional LC with triangular gallbladder anatomy), with 50 patients per group. The intraoperative blood loss, operation time, postoperative drainage tube indwelling time, hospitalization time, bile duct injury rate, operation conversion rate, and incidence of postoperative complications were recorded and compared between the two groups. The pain response and daily activities of the patients in the two groups were evaluated 48 h after the operation. RESULTS: The amount of intraoperative blood loss, postoperative drainage tube indwelling time, hospital stay, operation conversion rate, pain degree at 24 and 48 h after operation, bile duct injury incidence, and total postoperative complication rate were shorter or lower in the experimental group than those in the control group (p < 0.05). The Barthel index scores of both groups were higher 48 h after the operation than before the operation, and the experimental group was higher than the control group (p < 0.05). CONCLUSION: The ampulla-guided alignment in DLC surgery was more beneficial in promoting postoperative recovery, reducing postoperative pain response, reducing the incidence of postoperative complications, and reducing bile duct injury.

Combination of Biochar and Trichoderma harzianum Can Improve the Phytoremediation Efficiency of Brassica juncea and the Rhizosphere Micro-Ecology in Cadmium and Arsenic Contaminated Soil.

Phytoremediation is an environment-friendly method for toxic elements remediation. The aim of this study was to improve the phytoremediation efficiency of Brassica juncea and the rhizosphere soil micro-ecology in cadmium (Cd) and arsenic (As) contaminated soil. A field experiment was conducted with six treatments, including a control treatment (CK), two treatments with two contents of Trichoderma harzianum (T1: 4.5 g m-2; T2: 9 g m-2), one biochar treatment (B: 750 g m-2), and two combined treatments of T1B and T2B. The results showed Trichoderma harzianum promoted the total chlorophyll and translocation factor of Brassica juncea, while biochar promoted plant biomass compared to CK. T2B treatment showed the best results, which significantly increased Cd accumulation by 187.49-308.92%, and As accumulation by 125.74-221.43%. As a result, the soil's total Cd content was reduced by 19.04% to 49.64% and total As contents by 38.76% to 53.77%. The combined amendment increased the contents of soil available potassium, phosphorus, nitrogen, and organic matter. Meanwhile, both the activity of glutathione and peroxidase enzymes in plants, together with urease and sucrase enzymes in soil, were increased. Firmicutes (dominant bacterial phylum) and Ascomycota (dominant fungal phylum) showed positive and close correlation with soil nutrients and plant potentially toxic elements contents. This study demonstrated that phytoremediation assisted by biochar and Trichoderma harzianum is an effective method of soil remediation and provides a new strategy for enhancing plant remediation efficiency.

Upregulation of NUAK2: A novel prognostic marker in breast cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed neoplasm in women worldwide. New molecular biomarkers and effective prognostic models are being developed. This study aimed to investigate the clinical and prognostic significance of NUAK2 expression in patients with breast cancer. METHODS: The expression of NUAK 2 was examined in breast cancer cells and tissues by real-time PCR, western blotting, and immunohistochemical staining. CCK-8 and colony formation assays were performed to verify the effect of NUAK2 on the proliferation and tumor progression of breast cancer cells. A tumor formation assay in nude mice was performed to analyze the effect of NUAK2 on the tumorigenicity of breast cancer cells. RESULTS: The expression of NUAK2 in breast cancer tissues was higher than that in paracarcinoma and normal breast tissues. The overall survival of patients with high NUAK2 expression was significantly lower than that of patients with low NUAK2 expression. Multivariate analyses indicated that NUAK2 was an independent prognostic indicator of survival in breast cancer. In vitro experiments demonstrated that knocking down NUAK2 in breast cancer cells inhibited cell proliferation and tumor-forming ability, and overexpression of NUAK2 showed the opposite effects. NUAK2 overexpression promoted the tumorigenicity of breast cancer cells in vivo. CONCLUSION: These findings suggest that NUAK2 is involved in breast cancer development and progression. NUAK2 may be a valuable prognostic indicator in patients with breast cancer.

MicroRNA-378 inhibits hepatocyte apoptosis during acute liver failure by targeting caspase-9 in mice.

BACKGROUND: Acute liver failure (ALF) is a severe and potentially lethal clinical syndrome. It has been demonstrated that micro ribonucleic acids (miRNAs) are crucial mediators of nearly all pathological processes, including liver disease. OBJECTIVE: The present study investigates the role of miR-378 in ALF. An ALF mouse model was induced using intraperitoneal injections of d-galactosamine/lipopolysaccharide (d-GalN/LPS). A hepatocyte cell line and miR-378 analogue were used in vitro to investigate the possible roles of miR-378 in ALF. METHODS: The expressions of miR-378 and predicted target genes were measured via reverse transcription-quantitative polymerase chain reaction and western blotting, and cell apoptosis was assayed using flow cytometry. RESULTS: Compared with mice in the control group, the mice challenged with d-GalN/LPS showed higher levels of alanine aminotransferase, aspartate aminotransferase, tumour necrosis factor-alpha and interleukin-6, more severe liver damage and increased numbers of apoptotic hepatocytes. Hepatic miR-378 was distinctly downregulated, while messenger RNA and protein levels of cysteinyl aspartate specific proteinase 9 (caspase-9) were upregulated in the ALF model. Furthermore, miR-378 was downregulated in d-GalN/TNF-induced hepatocyte cells, and miR-378 was found to inhibit hepatocyte apoptosis by targeting caspase-9. CONCLUSION: Together, the present results indicate that miR-378 is a previously unrecognised post-ALF hepatocyte apoptosis regulator and may be a potential therapeutic target in the context of ALF.

Network Toxicology Guided Mechanism Study on the Association between Thyroid Function and Exposures to Polychlorinated Biphenyls Mixture.

Polychlorinated biphenyls (PCBs) are persistent and highly toxic pollutants, which can accumulate in organisms and produce toxic effects, especially damaging the function of thyroid hormones. So far, the molecular mechanism of PCBs mixture and their metabolites interfering with thyroid hormones has not been studied thoroughly except for individual compounds. In this study, PubMed, Web of Science, and STITCH databases were used to search PCBs and their corresponding target proteins. The intersection of PCBs and thyroid hormone dysfunction target proteins was obtained from GeneCards. The "compounds-targets-pathways" network was constructed by Cytoscape software. And KEGG and Go analyses were performed for key targets. Finally, molecular docking was used to verify the binding effect. Four major active components, five key targets, and 10 kernel pathways were successfully screened by constructing the network. Functional enrichment analysis showed that the interference was mediated by cancer, proteoglycans, PI3K-Akt, thyroid hormone, and FoxO signaling pathways. The molecular docking results showed that the binding energies were less than -5 kcal·mol-1. PCBs and their metabolites may act on the key targets of MAPK3, MAPK1, RXRA, PIK3R1, and TP53. The toxic effect of sulfated and methyl sulfone PCBs is greater. The method of screening targets based on the simultaneous action of multiple PCBs can provide a reference for other research. The targets were not found in previous metabolite toxicity studies. It also provides a bridge for the toxic effects and experimental research of PCBs and their metabolites in the future.

microRNA-497 prevents pancreatic cancer stem cell gemcitabine resistance, migration, and invasion by directly targeting nuclear factor kappa B 1.

OBJECTIVES: Cancer stem cells (CSCs) comprise a small population of cells in cancerous tumors and play a critical role in tumor resistance to chemotherapy. miRNAs have been reported to enhance the sensitivity of pancreatic cancer to chemotherapy. However, the underlying molecular mechanism requires better understanding. METHODS: Cell viability and proliferation were examined with CCK8 assays. Quantitative real-time polymerase chain reaction was executed to assess mRNA expression. StarBase database was used to select the target genes of miRNA, which were further affirmed by dual luciferase assay. Transwell assay was used to analyze cell invasion and migration. RESULTS: We proved that miR-497 could be obviously downregulated in pancreatic cancer tissues and CSCs from Aspc-1 and Bxpc-3 cells. In addition, inhibition of miR-497 evidently accelerated pancreatic CSC gemcitabine resistance, migration and invasion. Moreover, we revealed that nuclear factor kappa B 1 (NFκB1) was prominently upregulated in pancreatic cancer tissues and pancreatic CSCs, and NFκB1 was also identified as a direct target of miR-497. Furthermore, we demonstrated that overexpression of NFκB1 could also notably promote the viability, migration, and invasion of gemcitabine-treated pancreatic CSCs, but this effect could be partially abolished by miR-497 overexpression. CONCLUSIONS: Those findings suggest that miR-497 overexpression could suppress gemcitabine resistance and the metastasis of pancreatic CSCs and non-CSCs by directly targeting NFκB1.

MIR4435-2HG, miR-125b-5p, and Sema4D axis affects the aggressiveness of colorectal cancer cells.

INTRODUCTION: The purpose of this study is to elucidate the impact of long non-coding RNA (lncRNA) MIR4435-2HG/microRNA (miR)-125b-5p/ Semaphorins 4D (Sema4D) on colorectal cancer (CRC) cell propagation and migration. MATERIAL AND METHODS: Sema4D expression in 73 pairs of CRC tissues and matched adjacent normal tissues was measured by qRT-PCR and western blot and its association with pathological characteristics of CRC patients was analyzed by chi-square test. Also, the expression of MIR4435-2HG, miR-125b-5p and Sema4D in CRC cell lines was detected by qRT-PCR and Western blot. Knockdown or overexpression of MIR4435-2HG, miR-125b- 5p and Sema4D were separately performed in Caco-2 and LoVo cells, and the cell propagation, migration and invasiveness were detected by cell-counting kit 8, scratch, and transwell assays. RESULTS: LncRNA MIR4435-2HG and Sema4D were highly expressed, while miR-125b-5p expression was decreased in CRC tissues and cells. Knockdown of MIR4435-2HG/Sema4D or overexpression of miR-125b-5p inhibited CRC cell proliferation and aggressiveness; overexpression of MIR4435-2HG/Sema4D or knockdown of miR-125b-5p prompted the malignant behaviors of cancer cells. MIR4435-2HG and Sema4D competitively bound to miR-125b-5p. CONCLUSIONS: LncRNA MIR4435-2HG targets miR-125b-5p to upregulate Sema4D expression, and thus regulates CRC cell propagation, migration and invasiveness.

Level of LncRNA GAS5 and Hippocampal Volume are Associated with the Progression of Alzheimer's Disease.

Purpose: We evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer's disease (AD). Patients and Methods: One hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman's rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD. Results: The levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%. Conclusion: The results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.

YAP1 activation promotes epithelial-mesenchymal transition and cell survival of renal cell carcinoma cells under shear stress.

Renal cell carcinoma (RCC) is characterized by substantial vasculatures and increased fluid movement in tumor microenvironment, and the fluid shear stress modulates malignance, extravasation and metastatic seeding of tumor cells. However, the precise mechanism remains largely unclear. In this study, we found that low shear stress induced the Yes-associated protein (YAP1) activation and nuclear localization in RCC cells, as well as the downregulation of phosphorylated YAP1 at Ser127. Moreover, inhibition of ROCK or RhoA partially abolished YAP1 accumulation in the nucleus, and targeting YAP1 activation by small molecular inhibitor or genetic manipulation decreased the low shear stress-induced epithelial-mesenchymal transition (EMT) of RCC cells, and led to a decreased expression of N-cadherin as accompanied by downregulation of SNAIL1 and TWIST, accompanied by high shear stress-induced cell apoptosis. Salvianolic acid B, an aqueous component of danshen (Salvia miltiorrhiza), inhibited YAP1 and Hippo signaling activation, and abrogated low shear stress-induced EMT as a consequence. Taken together, our study suggests YAP1 is a fluid mechanosensor that transforms mechanical stimuli to cell signals, thereby facilitates anoikis resistance and tumor metastasis.

Application of multivariate statistical analysis and network pharmacology to explore the mechanism of Danggui Liuhuang Tang in treating perimenopausal syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui Liuhuang Tang (DGLHT), first recorded in "Lan-Shi-Mi-Cang" (written in 1276 AD), is a famous classical formula. In 2018, it was listed in the Catalogue of Ancient Classic and Famous Prescriptions (First Batch) formulated by the National Administration of Traditional Chinese Medicine and the National Medical Products Administration. Perimenopausal syndrome (PMS) refers to a series of syndromes with autonomic nervous system dysfunction and neuropsychological symptoms. The treatment of PMS demands non-hormonal drugs. Natural products are considered to be effective substitutes for the treatment of PMS. It is reported that DGLHT has not only good therapeutic effects but also higher safety and fewer side effects in the treatment of PMS. However, the mechanism of DGLHT in treating PMS is not clear. AIM OF THE STUDY: To explore the chemical basis and the mechanism of DGLHT in treating PMS. MATERIALS AND METHODS: Multivariate statistical analysis was used to analyze the difference of components in supernatant before and after compatibility of DGLHT based on LC-MS data. The qualitative analysis was performed on the precipitate formed in the decocting process using LC-MS while the quantitative analysis on the potential markers using LC-UV. Then, the potential markers were analyzed by network pharmacology. The regulatory effect of DGLHT on FSH, P and E2 were carried out in PMS rats. RESULTS: Five potential markers, epiberberine, coptisine, palmatine, berberine and baicalin, were screened from the analysis of compounds in the supernatant. Four complexes, composed of potential marker monomers, were identified in the sediment, including two that have not been reported. The key targets of potential markers include TNF, NOS3, EGFR, ESR1, PTGS2, AR, CDC42 and RPS6KB1. The top signaling pathways include the cGMP-PKG signaling pathway, PI3K-Akt signaling pathway and estrogen signaling pathway. DGLHT could call back the hormone levels of P and E2 in PMS rats. CONCLUSION: DGLHT active ingredients, epiberberine, coptisine, palmatine, berberine and baicalin contribute a lot to the therapeutic effect. And DGLHT takes effect by regulating hormones secreted by the ovary.

Abnormal Expression of Centromere Protein U Is Associated with Hepatocellular Cancer Progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, but its molecular mechanism is unclear. Abnormal expression of centromere protein U (CENPU) is closely related to diverse human cancers. The purpose of this article was to evaluate the function and potential mechanisms of CENPU in HCC development. METHODS: We performed bioinformatics analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter databases to investigate the clinical significance and prognostic value of CENPU in HCC. Western blotting and immunohistochemical staining were used to measure protein expression, while reverse transcription-quantitative polymerase chain reaction (qRT-PCR) was used to determine mRNA expression. Cell Counting Kit8 (CCK-8) and colony formation assays were conducted to examine cell proliferation. Transwell and wound healing assays were used to assess cell migration and invasion. Gene set enrichment analysis (GSEA) was used to explore the potential signaling pathways of CENPU involved in HCC. RESULTS: High expression of CENPU in HCC was predicted by public database analysis and indicated a poor prognosis. CENPU expression was significantly higher in HCC tissues and cells than in normal tissues and cell. In vitro, CENPU promoted the proliferation, migration, and invasion of HCC cells. GSEA results indicated that CENPU was linked to the Notch signaling pathway, and our research supported this prediction. CONCLUSION: CENPU promotes the malignant biological process of HCC and may be a promising target for HCC treatment.

Combining Network Pharmacology with Molecular Docking for Mechanistic Research on Thyroid Dysfunction Caused by Polybrominated Diphenyl Ethers and Their Metabolites.

Network pharmacology was used to illuminate the targets and pathways of polybrominated diphenyl ethers (PBDEs) causing thyroid dysfunction. A protein-protein interaction (PPI) network was constructed. Molecular docking was applied to analyze PBDEs and key targets according to the network pharmacology results. A total of 247 targets were found to be related to 16 PBDEs. Ten key targets with direct action were identified, including the top five PIK3R1, MAPK1, SRC, RXRA, and TP53. Gene Ontology (GO) functional enrichment analysis identified 75 biological items. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified 62 pathways mainly related to the regulation of the thyroid hormone signaling pathway, MAPK signaling pathway, PI3K-Akt signaling, pathways in cancer, proteoglycans in cancer, progesterone-mediated oocyte maturation, and others. The molecular docking results showed that BDE-99, BDE-153, 5-OH-BDE47, 5'-OH-BDE99, 5-BDE47 sulfate, and 5'-BDE99 sulfate have a good binding effect with the kernel targets. PBDEs could interfere with the thyroid hormone endocrine through multiple targets and biological pathways, and metabolites demonstrated stronger effects than the prototypes. This research provides a basis for further research on the toxicological effects and molecular mechanisms of PBDEs and their metabolites. Furthermore, the application of network pharmacology to the study of the toxicity mechanisms of environmental pollutants provides a new methodology for environmental toxicology.

The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo.

Objectives: Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Gö6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Gö6976 on CML. The objectives of this research were: (1) to explore the impact of Gö6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Gö6976 to normal cells and animals.Methods:K562 cells and CML mice were used to explore the effect of Gö6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Gö6976.Results: Cell experiments showed that Gö6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 µM and 10 µM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 µM. Animal experiments showed that 2.5 mg/kg Gö6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg.Discussion: Because of the direct inhibitory effect of Gö6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Gö6976 could become a new type of anti-CML medicine. And the further research is needed.Conclusion: Our findings verified that Gö6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.

Synergistic Effect of Ni/W/Cu on MgAl2O4 for One-Pot Hydrogenolysis of Cellulose to Ethylene Glycol at a Low H2 Pressure.

Nickel and tungsten, combined with copper, were incorporated into a magnesium aluminum spinel to form a multifunctional catalyst (Ni-W-Cu/MgAl2O4). Characterization results suggested that the adjacent Cu not only facilitated the reduction of W6+ to W5+ with substantial oxygen vacancies but also promoted the reducibility of the Ni species. Besides, the incorporation of Ni, W, and Cu into the support enhanced the catalytic acidity, as well as the L acid sites. The catalyst exhibited a strong synergistic effect between the three metals and the support, resulting in higher catalytic activity for the one-pot hydrogenolysis of cellulose to ethylene glycol. High cellulose conversion (100%) and ethylene glycol yield (52.8%) were obtained, even under a low H2 pressure of 3 MPa.