Exploring the mechanism and experimental validation of Fuzi Lizhong Tang in treating gastric cancer based on network pharmacology and molecular docking.

OBJECTIVE: This study aimed to explore the mechanism of Fuzi Lizhong Tang (FZLZT) in treating gastric cancer using network pharmacology and molecular docking, and to validate the results through in vitro experiments. MATERIALS AND METHODS: Active ingredients and target genes of FZLZT were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, while disease targets of gastric cancer were collected from GeneCards, OMIM, and DrugBank databases. The "herb-active ingredient-target gene" network was constructed using Cytoscape software, and core active ingredients were obtained through topological analysis. Protein-protein interaction analysis was performed using the STRING database, and core targets were obtained through topological analysis. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed using the DAVID database. Molecular docking was conducted using AutoDock Vina software to verify the interaction between core ingredients and core targets. Cholecystokinin octapeptide (CCK-8) assay was used to determine the proliferation inhibition effect of FZLZT on AGS, BGC823, HGC-27, MGC-803, and SGC-7901 gastric cancer cell lines, and ANNEXIN V-FITC/PI double staining combined with flow cytometry was used to measure the cell apoptosis rate. RESULTS: Network pharmacology analysis revealed 117 active ingredients and 261 target genes of FZLZT, and 211 overlapping targets with gastric cancer. Ten core active ingredients were identified through topological analysis, including quercetin, 7-methoxy-2-methyl isoflavone, kaempferol, luteolin, naringenin, isorhamnetin, quercetagetin, glycyrrhizic acid A, ß-sitosterol, and medioresinol. GO and KEGG enrichment analysis showed that the mechanism of FZLZT in treating gastric cancer mainly involves cancer, inflammation, metabolism, and blood rheology-related pathways, and may act through 7 core targets (CDKN1A, MYC, MAPK1, MAPK14, RB1, RELA, and STAT3). Molecular docking results further confirmed the prediction of network pharmacology. In vitro experiments showed that FZLZT inhibited the proliferation of all five gastric cancer cell lines, with the strongest effect on SGC-7901 cells, and induced apoptosis in SGC-7901 cells. CONCLUSIONS: FZLZT has a multi-component, multi-target, and multi-pathway characteristic in treating gastric cancer. Its active ingredients may regulate the expression of proteins such as CDKN1A, MYC, MAPK1, MAPK14, RB1, RELA, and STAT3 to activate cancer-related signaling pathways to achieve its therapeutic effect.

RESEARCH ARTICLE Molecular cloning and expression analysis of a matrix Gla protein gene in the spinyhead croaker, Collichthys lucidus.

The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics. The Gla domain and the invariant unit ErraEtCedyspC, which has been identified in all known vitamin K-dependent vertebrate proteins, were highly conserved in Cl-MGP, suggesting that it uses the same mechanism to function as the known proteins. An alignment analysis revealed that Cl-MGP had the highest identity with Larimichthys crocea (93%), which had lost five amino acid residues in the C-terminal. A quantitative real-time polymerase chain reaction revealed that Cl-MGP expression was highest in the gill, followed by the cholecyst and spleen, with almost no expression in the blood, muscle, or testes. The high Cl-MGP expression in the gill is similar to that observed in other fish species, but the relatively high expression found in the cholecyst and spleen is not seen in all species. Future studies should investigate the tissue distributions of both mRNA and proteins in different species, in order to understand the function and evolution of MGP in different species.

Effect of a carbohydrate-containing late-evening snack on energy metabolism and fasting substrate utilization in adults with acute-on-chronic liver failure due to Hepatitis B.

BACKGROUND/OBJECTIVES: This study investigates the effects of a carbohydrate (CHO; lotus-root starch) predominant, late-evening snack (LES), containing 200 kcal (50 g CHO) on fasting resting energy expenditure (REE) and nutrient oxidation in hospitalized adults with acute-on-chronic liver failure (ACLF). SUBJECTS/METHODS: Adults with ACLF were randomized to receive daily LES (treatment; n=35) or standard care (n=35; non-supplemented control) for 14 days. REE and respiratory quotient (RQ) were measured by indirect calorimetry, nutrient oxidation (CHO, protein and fat), intake and biochemical parameters were measured in both groups at baseline and after 14 days using validated techniques. Disease severity was measured using the model for end-stage liver disease (MELD). RESULTS: No significant differences in macronutrient intake, anthropometric, demographic characteristics or MELD scores were observed between groups at baseline (P>0.05). Fasting RQ was significantly higher in the LES supplemented verses the control group after 2 weeks (P=0.02). CHO oxidation was significantly higher (P=0.001) and fat oxidation (P=0.02) was lower in the LES-supplemented group when compared with controls after 2 weeks. Fasting RQ and REE in the LES-supplemented group increased significantly (0.83 verses 0.88; P=0.007/1301±409 vs 1687±718 kcal/day; P=0.02) in patients with MELD scores 30 when compared with patients with MELD scores >30 (0.82 verses 0.84; P=0.27/ 1361±405 vs 1437±429 kcal/day; P=0.67) after supplementation. CONCLUSIONS: A carbohydrate-predominant LES is associated with increases in fasting carbohydrate oxidation, REE and reductions in fat oxidation in adults with ACLF. Therapeutic strategies utilizing LES may promote improved nutritional status in adults with ACLF.

[Conservative therapy of combining laparoscopy and Chinese medicine for ectopic pregnancy].

44 cases of ectopic pregnancy have been treated conservatively by combining laparoscopy with TCM and all were successful. After confirmatory diagnosis was made under laparoscope low dose (5-15mg) of Methotrexate (MTX) was injected into tubal swelling, as well as taking modified Huo-Luo-Xiao-Ling Dan orally and using Ding-Tong paste and Zi-Gong pill externally, it not only improved the function of herbal medicine that was not potent enough to kill active embryo, but also gave full play of TCM which could remove stasis and masses by promoting blood circulation to assist in killing the embryo. The successful rate (100%) of combined therapy was significantly higher than that (78.2%) of control group (using TCM only, P < 0.01). Comparing with the two groups in successful cases, the mean serum hCG concentrations per day of combined therapy lowered faster than that of control group (P < 0.005), the mean time of abdominal pain disappearance and hospitalized period of combined group were shorter (P < 0.01). In a word, this combined therapy is a simple and safe method which could preserve reproductive function to the maximum.

[Effect of liuwei dihuang granules, pills and decoction on contents of cAMP, E2, T, Zn and Cu in plasma of renal yin deficient patients].

Experiments showed that in patients of renal yin deficiency who took orally Liuwei Dihuang granules for 4 weeks, the contents of cAMP, E2, Zn and Cu were found mankedly lower, but the contents of T mankedly higher than before using the drugs. This indicates that the granules are equally effective as pills and decoction.

Cadmium exposure and health effects among residents in an irrigation area with ore dressing wastewater.

About 0.05 mg Cd l-1 was found in the irrigation water contaminated by the wastewater discharged from tungsten ore dressing plants, and about 1 mg Cd kg-1 was found in irrigated acid soils. The main sources of cadmium intake by residents of the polluted areas are agricultural products. The average intake of cadmium was 367-382 micrograms day-1, and for smokers 417 micrograms day-1. Among the residents who have been exposed to cadmium for more than 25 years, cadmium absorption (urinary cadmium greater than or equal to 10 micrograms g-1 creatine) was 60% and an early effect on the target organ (urinary cadmium greater than or equal to 15 micrograms g-1 creatinine and urinary beta 2-microglobulin greater than 500 micrograms g-1 creatinine) was detected in 17% of the sample of 433 persons. Levels of urinary cadmium and blood cadmium exceeded the critical value in the exposed group. The concentrations of urinary calcium, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase were significantly higher in residents of contaminated areas than in those of control areas. Case-control study of the residents shows that many have suffered from a nephropathy with tubulo-interstitial abnormalities. Owing to the combined cadmium effect, the cases with fractional beta 2-microglobulin excretion greater than 0.10 were 46% in the exposed population, and were much higher than that in the control group (20.3%).

The effect of radix Salviae miltiorrhizae on vasoactive intestinal peptide in cerebral ischemia: an animal experiment.

The levels of vasoactive intestinal peptide (VIP) in three regions of rat brain were assayed in 62 rats. Bilateral common carotid artery ligation was done in 50 rats. Half an hour before ligation 26 rats were given 10 g/kg of Radix Salviae Miltiorrhizae (RSM); 24 rats were given same volume of normal saline as controls. A sham operation was done in 12 rats. Half an hour (n = 30) and 3 hours (n = 32) after operation, the rats were quickly decapitated. VIP levels were assayed in cerebral cortex, hippocampus and caudate nucleus. In salin-treated animals, VIP levels of cerebral cortex and caudate nucleus at 3 hour group were significantly decreased compared with the sham-operated group. No significant difference was found between RSM-treated and sham-operated groups. The preliminary results suggest that VIP may be involved in the pathophysiological procedures of cerebral ischemia and RSM may attenuate the dysfunction of VIP during cerebral ischemia.

Cerebral infarction improved by safflower treatment.

The effect of safflower on cerebral infarction was studied in 152 Mongolian gerbils. Sixty-three animals were evaluated neurological deficit over 8 hours postoperation, then sacrificed and NE, DA and 5-HT contents of each cerebral hemisphere and brain stem were determined. NE, DA and 5-HT of hemisphere ipsilateral to the ligated artery in untreated animals declined significantly compared with sham-operated animals and safflower-treated gerbils. There was no significant difference between safflower-treated and sham-operated animals in NE, DA and 5-HT contents. The mean stroke index at 8 hours in safflower treated animals was 2.1 +/- 0.7, whereas untreated gerbils was 7.8 +/- 1.9 (P less than 0.01). Eighty-nine animals were followed up for 5 days, the safflower-treated animals showed a benign clinical course and mortality rate was reduced by 29.7% (6/34 vs. 26/55) in safflower-treated animals compared with untreated animals (P less than 0.01). Safflower has a protective and beneficial effect on cerebral ischemia induced in Mongolian gerbils.