Integration of mult-omics and nucleotide metabolism reprogramming signature analysis reveals gastric cancer immunological and prognostic features.

BACKGROUND: Gastric cancer is a frequent and lethal solid tumor that has a poor prognosis and treatment result. Reprogramming of nucleotide metabolism is a characteristic of cancer development and progression. METHODS: We used a variety of machine learning techniques to create a novel nucleotide metabolism-related index (NMRI) using gastric cancer sample data obtained from the TCGA and GEO databases. This index is based on genes associated to nucleotide metabolism. Gastric cancer patients were categorized into high and low NMRI groups based on NMRI results. The clinical features, tumor immune microenvironment, response to chemotherapy, and response to immunotherapy were then thoroughly examined. In vitro experiments were then used to confirm the biological role of SERPINE1 in gastric cancer. RESULTS: The four nucleotide metabolism-related genes that make up NMRI (GAMT, ORC1, CNGB3, and SERPINE1) were verified in an external dataset and are a valid predictor of prognosis for patients with gastric cancer. The high NMRI group was more responsive to immunotherapy and had greater levels of immune cell infiltration than the low NMRI group. The proliferation and migration of stomach cancer was shown to be decreased by SERPINE1 knockdown in vitro. CONCLUSIONS: This study's NMRI can reliably predict a patient's prognosis for stomach cancer and pinpoint the patient group that will benefit from immunotherapy, offering important new information on the clinical treatment of stomach cancer.

Acupressure in the treatment of patients with mild infection of COVID-19 omicron variant: A prospectively observational study.

During the coronavirus disease 2019 epidemic, acupressure has been widely used as a complementary treatment for coronavirus disease 2019 in China, but its safety and effectiveness have not been determined until now. This was a prospectively observational study containing 400 cases of mild infection of Omicron who were admitted to Chongming Flower Expo Makeshift Hospital from April 1, 2022 to May 1, 2022. Patients were assigned to receive basic treatment or a combination with acupressure treatment (5 minutes per acupoint, at least twice daily), from admission to discharge. The conversion time of viral RNA assay, the recovery time of symptoms and the clinical cure rate at day 7 were compared in 2 groups. All cases were included in the final analysis. The time to conversion of viral RNA assay (6 vs 7 days, P < .001) and time to symptom recovery (2 vs 4 days, P < .001) were markedly shortened in the acupressure treatment group compared to controls. The time to recovery from individual symptoms of coughing, a sore throat, a fever, fatigue, poor appetite, and insomnia were shorter in the treatment group compared to the control (all P < .05), but there was no statistical difference in reducing the recovery time from headache, muscle ache, anxiety, loss of taste between 2 groups (all P > .05). In addition, acupressure therapy also revealed a higher clinical cure rate at day 7 than basic treatment alone (91% vs 65%, P < .001) and reported no serious adverse events. This study provided evidence for acupressure therapy in treatment of Omicron infection concerning the viral load disappearance and the clinical symptoms improvements. Findings were expected to help guide efforts to position acupressure therapy as a therapeutic option for patients with Omicron variant.

Iterative mutagenesis induced by atmospheric and room temperature plasma treatment under multiple selection pressures for the improvement of coenzyme Q10 production by Rhodobacter sphaeroides.

CoQ10, which has been widely applied in medicine by dietary supplement, possesses important functions in antioxidant process and bioenergy generation. Iterative mutagenesis introduced by atmospheric and room temperature plasma (ARTP) treatment was studied to improve the coenzyme Q10 (CoQ10) production of Rhodobacter sphaeroides (R. sphaeroides), and multiple selection pressures including vitamin K3 (VK3), Na2S and benzoic acid (BA) were adopted for the first time. After two rounds of mutation and screening, a mutant strain R.S 17 was obtained, and the product titer was increased by 80.37%. The CoQ10 titer and cell density reached 236.7 mg L-1 and 57.09 g L-1, respectively, in the fed-batch fermentation, and the CoQ10 content was 22.1% higher than that of the parent strain. In addition, the spectral scanning results indicated the metabolic flux improvement contributing to the CoQ10 production in R.S 17, and the genetic stability was validated. Based on the iterative mutagenesis introduced by ARTP under multiple selection pressures, the promotion of CoQ10 production by R. sphaeroides was achieved. The significant improvement in fermentation performances and the good genetic stability of R.S 17 indicate a potential way for the efficient biosynthesis of CoQ10.

Two new pregnane steroidal glycosides from Cynanchum taihangense.

As our ongoing chemical investigation, two new pregnane steroidal glycosides, cynataihosides G (1), with a new aglycone, and H (2) were isolated from the 95% ethanol extract of Cynanchum taihangense. Their structures were elucidated on the basis of 1 D and 2 D NMR spectral data, HR-ESI-MS analysis and qualitative chemical methods. The compounds were subjected to detect the cytotoxicity against three human tumor cell lines (HL-60, THP-1 and PC-3). The compounds displayed no significant cytotoxicity.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1672682.

Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 cooperates with enhancer of zeste homolog 2 to promote hepatocellular carcinoma development by modulating the microRNA-22/Snail family transcriptional repressor 1 axis.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an oncogenic long noncoding RNA that has been found to promote carcinogenesis and metastasis in many tumors. However, the underlying role of MALAT1 in the progression and metastasis of hepatocellular carcinoma (HCC) remains unclear. In this study, aberrantly elevated levels of MALAT1 were detected in both HCC specimens and cell lines. We found that knockdown of MALAT1 caused retardation in proliferation, migration, and invasion both in vivo and in vitro. Mechanistic investigations showed that Snail family transcriptional repressor 1 (SNAI1) is a direct target of microRNA (miR)-22 and that MALAT1 modulates SNAI1 expression by acting as a competing endogenous RNA for miR-22. Inhibition of miR-22 restored SNAI1 expression suppressed by MALAT1 knockdown. Furthermore, MALAT1 facilitated the enrichment of enhancer of zeste homolog 2 (EZH2) at the promoter region of miR-22 and E-cadherin, which was repressed by MALAT1 knockdown. Cooperating with EZH2, MALAT1 positively regulated SNAI1 by repressing miR-22 and inhibiting E-cadherin expression, playing a vital role in epithelial to mesenchymal transition. In conclusion, our results reveal a mechanism by which MALAT1 promotes HCC progression and provides a potential target for HCC therapy.

Three new tetralol analogs from soil-derived fungus Myrothecium verrucaria with anti-inflammatory activity.

Three new tetralol analogs, myrochromanols A-C (1-3), together with 11 known trichothecenes (4-14), were isolated from a soil fungus Myrothecium verrucaria HL-P-1. The structures of the three new compounds were elucidated by extensive spectroscopic analysis including HRESIMS, NMR, and ECD calculation. All of the new compounds were tested for their anti-inflammatory activity and cytotoxicity. Compounds 1 and 3 inhibited lipopolysaccharide (LPS)-induced NO production in BV2 cells with IC50 values of 26.04 and 25.80 µM, respectively.

Two new C21 steroidal glycosides isolated from Cynanchum komarovii.

The present study was designed to further investigate the C21 steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC50 values ranging from 16.6 to 26.3 µmol·L-1, compared to the positive control 5-fluorouracil (6.4 µmol·L-1).

Optimization of Ag coated hydrogen silsesquioxane square array hybrid structure design for surface-enhanced Raman scattering substrate.

A computer-automated design process for a surface-enhanced Raman scattering (SERS) substrate using a particle swarm optimization algorithm is proposed. Nanostructured Ag coated hydrogen silsesquioxane nanopillar arrays of various sizes for SERS substrate applications are fabricated by direct Ag film deposition on substrates patterned by electron beam lithography and are investigated systematically. Good agreement is demonstrated between experimental and simulation results. The absorption spectra, charge distributions, and electric field distributions are calculated using finite-difference time-domain simulations to explain the field enhancement mechanism and indicate that this enhancement originates from plasmon resonance. Our work provides a guide towards optimum SERS substrate design.

EZH2 promotes hepatocellular carcinoma progression through modulating miR-22/galectin-9 axis.

BACKGROUND: Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. METHODS: Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ. Bioinformatics analysis and luciferase reporter assay were utilized to confirmthe binding ofmiR-22 to the 3' untranslated region (3'-UTR) of galectin-9. The methylation status of miR-22 promoter was analyzed by MSP (Methylation specific PCR) and BSP (bisulfite sequencing PCR), while chromatin immunoprecipitation (ChIP) assay identify the occupation status of EZH2 and H3K27me3 at the promoter. Furthermore, the effect of ectopic expression of galectin-9 and miR-22 on cell proliferation, migration, invasion and cell apoptosis was assessed by using CCK-8, transwell assays and flow cytometric analysis, respectively. RESULTS: IFN-γ induces up-regulation of galectin-9 and EZH2 in HCC cell lines. Galectin-9 is a target of miR-22 and EZH2 facilitates galectin-9 expression by tri-methylation of H3K27 on miR-22 promoter but not hyper-methylation status of DNA. MiR-22 overexpression suppressed HCC cell growth, invasion, and metastasis both in vitro and in vivo. Interestingly, galectin-9 also exhibited antitumor effects, and restoring galectin-9 expression in miR-22 overexpressing cells strengthened its antitumor effects. CONCLUSIONS: These findings indicated that EZH2 facilitates galectin-9 expression by epigenetically repressing miR-22 and that galectin-9, which is known as an immunosuppressant, also functions as a tumor suppressor in HCC.

Isolation and structure elucidation of a new compound from the fungus Aspergillus flavipes PJ03-11.

A new diphenyl ether 3-methylpentyl-2, 4-dichloroasterrate (2), along with a known diphenyl ether butyl 2, 4-dichloroasterrate (1) were isolated from the metabolites of a wetland fungus Aspergillus flavipes. PJ03-11. The structures of 1 and 2 were determined by extensive NMR and HR-ESI-MS experiments. Compounds 1 and 2 showed weak cytotoxic activity, but both of them showed no antimicrobial activity.

Structure determination of two new C21 steroidal glycosides from Cynanchum komarovii.

Two new 13,14:14,15-disecopregnane-type C21 steroidal glycosides, namely komarosides R (1) and S (2), along with four known compounds (3-6), were obtained from the 95% ethanol extract of the whole herbs of Cynanchum komarovii Al.Iljinski (Asclepiadaceae). The structures of new compounds were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. Compounds 1 and 2 showed potent inhibitory activities against human leukemia cell line (HL-60) with IC50 values being 6.2 and 17.6 µM, respectively, compared to the positive control 5-fluorouracil (6.4 µM).

One pair of new cyclopentaisochromenone enantiomer from Alternaria sp. TNXY-P-1 and their cytotoxic activity.

One pair of new cyclopentaisochromenone derivatives, (+)-(S)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1a) and (-)-(R)-6-hydroxy-1,8-dimethoxy-3a-methyl-3,3a-dihydrocyclopenta[c]isochromene-2,5-dione (1b), together with seven known analog 2‒8, were isolated from a rice solid culture of the endophytic fungus Alternaria sp. TNXY-P-1, obtained from fresh leaf of Arisaema heterophyllum. Their structures were elucidated on the basis of detailed 1D, 2D NMR, and HRESIMS analysis. Among them, compounds 1a and 1b were enantiomers separated from 1 by chiral HPLC. The absolute configurations of 1a and 1b were assigned by quantum chemical calculations of the electronic circular dichroic spectra. All isolated compounds were evaluated for cytotoxic activities. Interestingly, enantiomers (+)-1a and (-)-1b showed distinct selective antitumor activities against HL-60 cell lines with IC50 values of >200, 75.3 µM, respectively.

Two new 14, 15-secopregnane-type steroidal glycosides from the roots of Cynanchum limprichtii.

Two new steroidal glycosides 1 and 2, along with three known ones (3-5), were isolated from the 95% ethanol extract of the roots of Cynanchum limprichtii Schltr. The structure of the new compounds was elucidated as 3-O-α-L-diginopyranosyl-(1→4)-ß-D-digitoxopyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-ß-D-thevetopyranosyl-14, 16:15, 20:18, 20-triepoxy-14, 15-secopregn-4, 6, 8 (14)-triene (1) and 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-digitoxopyranosyl- (1→4)-ß-D-3-demethyl-2-deoxythevetopyranosyl-14, 16: 15, 20: 8, 20-triepoxy-14, 15-secopregn-5, 8 (14)-diene (2) on the basis of spectroscopic analysis together with acidic hydrolysis. All compounds showed cytotoxic activity against the human cancer cell line HL60, with IC50 values of 55.36, 65.41, 17.88, 17.68 and 33.5 µM, respectively. While, only compound 3 showed cytotoxicity against the Caco-2 cell line, with an IC50 value of 67.47 µM.

C21 steroidal glycosides from Cynanchum taihangense.

Two new C21 steroidal glycosides, cynataihosides E (1) and F (2), together with a known one, sublanceoside H2 (3), were isolated from Cynanchum taihangense. The aglycone of cynataihoside F (2) was also a new compound. Their structures were elucidated on the basis of NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. Their cytotoxic activities against three human tumor cell lines (HL-60, THP1, and Caco2) were reported.

α-Pyrone derivatives with cytotoxic activities, from the endophytic fungus Phoma sp. YN02-P-3.

Four new α-pyrone derivatives phomones C-F (1-4) together with four known compounds (5-8) were isolated from the endophytic fungus Phoma sp. YN02-P-3. Compound 1 is the first example of 6-α,ß-unsaturated ester-2-pyrone dimers via intermolecular symmetrical [2+2] cycloaddition. The chemical structures of these compounds were determined from spectroscopic data (1D/2D NMR, MS and IR). The acetylated product (9) of 1 along with compounds 1-8 were then tested for their cytotoxicity against HL-60, PC-3 and HCT-116 cell lines. Compounds 2, 3, 5 and 9 with acetyl groups showed significant inhibitory activities against the three cell lines with IC50 values in the range 0.52-9.85µM. while compounds 1, 4 and 6-8 that possess no acetyl group showed no inhibitory activity (IC50>50µM), indicating that the acetyl group at 10- or 12- are essential for their cytotoxic activities. The structure-activity relationships of these phomones were also reported.

Anterior Approach to Improve the Prognosis in HCC Patients Via Decreasing Dissemination of EpCAM+ Circulating Tumor Cells.

BACKGROUND: It is supposed that the improvement of prognosis in hepatocellular carcinoma (HCC) patient by anterior approach for liver resection was related to the decreasing hematogenic dissemination of circulating cancer cells. METHODS: The EpCAM+ circulating tumor cells (CTCs) were detected in HCC patients having liver resection with either anterior approach (AA) or conventional approach (CA). The relation of CTCs to the 2-year recurrence and survival after surgery was investigated. RESULTS: Overall, patients with ≥3.5 CTCs had much higher recurrence rate than those with <3.5 CTCs (62.0 vs. 18.0%, P = 0.001). Less CTCs were detected in AA group than that in CA group (mean, 2.1 vs. 3.0; median, 1.2 vs. 3.5; all P = 0.001). The 2-year recurrence rate in AA group was much lower than in CA group (27.1 vs. 44.9%, P = 0.009). The 2-year survival rate in AA group was much higher than in CA group (83.3 vs. 66.7%, P = 0.001). The CTCs in >5 cm AA group were much less than that in >5 cm CA group (3.7 vs. 2.4, P = 0.002). Moreover, the 2-year recurrence rate in >5 cm AA group was much lower than that in >5 cm CA group (29.2 vs. 54.7%, P = 0.001). Also, the 2-year survival rates in >5 cm AA group were much higher than that in >5 cm CA group (72.9 vs. 49.1%, P = 0.01). By multivariate analysis, CA is one of the independent risk factors for poor prognosis in HCC patients after liver resection. CONCLUSIONS: Like the liver-directed therapies, AA can reduce the dissemination of CTCs, especially in patients with large-size HCC (>5 cm) and successively improve the early prognosis.

Three new amino acid derivatives from edible mushroom Pleurotus ostreatus.

Three new amino acid derivatives, oxalamido-L-phenylalanine methyl ester (1), oxalamido-L-leucine methyl ester (2), and lumichrome hydrolyzate (3), together with nine known compounds (4-12), were isolated from the solid culture of edible mushroom Pleurotus ostreatus. Their structures were elucidated on the basis of extensive spectroscopic analysis. The absolute configurations of 1 and 2 were established by the chiral synthesis and confirmed by circular dichroism (CD) analysis of their total synthesis products and natural isolates. All new compounds were evaluated for their antioxidant effects, antimicrobial activities, and cytotoxic activity. Compounds 1-3 showed weak antifungal activities against Candida albicans with minimum inhibitory concentration (MIC) value of 500 µg/ml.

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone and a new isocoumarin isolated from the endophytic fungus Phoma sp. YN02-P-3.

A novel 3,4-dihydronaphthalen-1(2H)-one with spiro-butyrolactone phomol (1) and a new isocoumarin phomasatin (2), together with two known compounds (3-4) were isolated from the solid culture of the endophytic fungus Phoma sp. YN02-P-3. Their structures including the absolute configurations were characterized on the basis of extensive 1D, 2D NMR (HSQC, HMBC, NOESY), MS, and CD spectral data. Compound 1 showed selective cytotoxic activity against HL-60 cell line with the IC50 value of 29.05 µM.

Distinct Recurrence Risk Factors for Intrahepatic Metastasis and Multicenter Occurrence After Surgery in Patients with Hepatocellular Carcinoma.

BACKGROUND AND OBJECTIVES: Intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC) includes intrahepatic metastasis (IM) and multicenter occurrence (MO). The risk factors for these two types of intrahepatic recurrence have not been well defined. METHODS: The type of intrahepatic recurrence was determined based on histopathological features of 93 HCC patients who underwent a repeat hepatectomy for recurrent HCC. Various clinical and pathological factors were analyzed to define distinct risk factors for different types of intrahepatic recurrence. RESULTS: The recurrence rates at 1, 2, 3, 5, and 8 years postoperatively were 22.4, 42.9, 61.2, 85.7, and 100 %, respectively, in patients with IM and 5.0, 25.0, 45.5, 67.5, and 100 %, respectively, in patients with MO (p = 0.005). A total of 16 clinical and pathological factors were tested in univariable and multivariable analyses. We found that large-size tumor (>5 cm), multiple tumors (two or more), and vascular invasion were significantly associated with IM recurrence, and liver cirrhosis and Ishak hepatic inflammatory activity were highly associated with MO recurrence. In addition, blood transfusion and a high hepatitis B virus (HBV)-DNA load (>2000 IU/ml) were independent risk factors common to both IM and MO recurrences. CONCLUSIONS: IM and MO recurrences were associated with distinct risk factors, while blood transfusion and high HBV-DNA load (>2000 IU/ml) were independent risk factors common to both IM and MO recurrences.

Three New Butenolides from the Fungus Aspergillus sp. CBS-P-2.

Three new butenolides aspernolides H-J (1-3) together with seven known ones (4-10) were isolated from the fungus Aspergillus sp. CBS-P-2. Their chemical structures were established on the basis of 1D- and 2D-NMR spectroscopic data, HR-ESI-MS analysis, and their absolute configuration were determined by circular dichroism (CD) analysis. All the compounds were evaluated for the antioxidant effects by DPPH and ABTS methods, the antitumor activities against four human tumor cell lines (HL-60, ASPC1, HCT-116 and PC-3) and antimicrobial activities. Compounds 4-10 showed significant activity against DPPH (IC50 = 15.9-34.3 µM) and compounds 1-10 exhibited significant ABTS free radical scavenging activity (IC50 = 2.8-33.1 µM). Compounds 2, 5 and 11 showed potent cytotoxic activities against HL-60 cell lines with IC50 values of 39.4, 13.2 and 16.3 µM, respectively. Compound 10 showed good antimicrobial activity against Staphylococcus aureus with minimum inhibitory concentration (MIC) of 21.3 µM.