[Effect of STIL on the Gene Expression Profile of Gastric Cancer Cells].

Objective To explore the molecular mechanism underlying gastric carcinogenesis and progression by using gene expression profiling array together with bioinformatics. Methods Lentivirus short hairpin RNA targeting STIL(ShSTIL)and scrambled sequence RNA(ShCon)were transduced into the gastric cancer cell line SGC-7901.RNA extraction,complementary DNA synthesis,construction of biotin-labelled amplified RNA probes,and hybridization with gene expression profile were consecutively performed.We collected corresponding data and analyzed differentially expressing genes(DEGs),followed by the analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment,transcription factor regulating network,and protein-protein interacting networks. Results Compared with ShCon,a total of 417 and 87 genes were respectively down-regulated and up-regulated,respectively,in the ShSTIL group(P<0.05,fold change>1 or <-1).GO and KEGG enrichment analysis indicated that genes regulated by STIL were localized in cytoplasm,extracellular exosome,Golgi apparatus and various biomembranes,and were implicated in the ubiquitin-mediated proteolysis,P53 signaling pathway,and pathways regulating pluripotency of stem cells.Evaluation on genes enriched in KEGG pathways,regulation of transcription factors,and protein-protein interacting network demonstrated that IGF1R,STUB1,SKP2,and FOXO1 were localized at the centre of the network and played a key role in the development and progression of gastric cancer. Conclusion Through the protein-protein interactions,STIL may activate E3 ubiquitin ligase STUB1 or SKP2,promote the proteolysis of FOXO1-a transcription factor,regulate the expression of IGF1R,and thus promote gastric carcinogenesis and progression.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. AIM: To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. METHODS: The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. RESULTS: Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). CONCLUSION: The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

A strategy to discover lead chemome from traditional Chinese medicines based on natural chromatogram-effect correlation (NCEC) and natural structure-effect correlation (NSEC): Mahonia bealei and Mahonia fortunei as a case study.

Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC50 values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.

Beneficial effects of a novel shark-skin collagen dressing for the promotion of seawater immersion wound healing.

BACKGROUND: Wounded personnel who work at sea often encounter a plethora of difficulties. The most important of these difficulties is seawater immersion. Common medical dressings have little effect when the affected area is immersed in seawater, and only rarely dressings have been reported for the treatment of seawater-immersed wounds. The objective of this study is to develop a new dressing which should be suitable to prevent the wound from seawater immersion and to promote the wound healing. METHODS: Shark skin collagen (SSC) was purified via ethanol de-sugaring and de-pigmentation and adjusted for pH. A shark skin collagen sponge (SSCS) was prepared by freeze-drying. SSCS was attached to an anti-seawater immersion polyurethane (PU) film (SSCS + PU) to compose a new dressing. The biochemical properties of SSC and physicochemical properties of SSCS were assessed by standard methods. The effects of SSCS and SSCS + PU on the healing of seawater-immersed wounds were studied using a seawater immersion rat model. For the detection of SSCS effects on seawater-immersed wounds, 12 SD rats, with four wounds created in each rat, were divided into four groups: the 3rd day group, 5th day group, 7th day group and 12th day group. In each group, six wounds were treated with SSCS, three wounds treated with chitosan served as the positive control, and three wounds treated with gauze served as the negative control. For the detection of the SSCS + PU effects on seawater-immersed wounds, 36 SD rats were divided into three groups: the gauze (GZ) + PU group, chitosan (CS) + PU group and SSCS + PU group, with 12 rats in each group, and two wounds in each rat. The wound sizes were measured to calculate the healing rate, and histomorphology and the immunohistochemistry of the CD31 and TGF-ß expression levels in the wounded tissues were measured by standard methods. RESULTS: The results of Ultraviolet-visible (UV-vis) spectrum, Fourier-transform infrared (FTIR) spectrum, circular dichroism (CD) spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and amino acid composition analyses of SSC demonstrated that SSC is type I collagen. SSCS had a homogeneous porous structure of approximately 200 µm, porosity rate of 83.57% ± 2.64%, water vapor transmission ratio (WVTR) of 4500 g/m2, tensile strength of 1.79 ± 0.41 N/mm, and elongation at break of 4.52% ± 0.01%. SSCS had significant beneficial effects on seawater-immersed wound healing. On the 3rd day, the healing rates in the GZ negative control, CS positive control and SSCS rats were 13.94% ± 5.50%, 29.40% ± 1.10% and 47.24% ± 8.40%, respectively. SSCS also enhanced TGF-ß and CD31 expression in the initial stage of the healing period. The SSCS + PU dressing effectively protected wounds from seawater immersion for at least 4 h, and accelerated re-epithelialization, vascularization and granulation formation of seawater-immersed wounds in the earlier stages of wound healing, and as well as significantly promoted wound healing. The SSCS + PU dressing also enhanced expression of TGF-ß and CD31. The effects of SSCS and SSCS + PU were superior to those of both the chitosan and gauze dressings. CONCLUSIONS: SSCS has significant positive effects on the promotion of seawater-immersed wound healing, and a SSCS + PU dressing effectively prevents seawater immersion, and significantly promotes seawater-immersed wound healing.

[Effects of mixed cypermethrin and methylparathion on endocrine hormone levels and immune functions in rats: I. Dose-response relationship].

OBJECTIVE: To study dose-response relationship effects of mixed cypermethrin and methyl parathion on reproductive hormones, thyroid hormones, and immune functions in rats. METHODS: Eighty 2-month old Wistar rats (40 males and 40 females) were divided randomly by bodyweight into 4 groups. Four doses (0, 1/600 LD50, 1/135 LD50 and 1/30 LD50) were chosen for the combined exposure representing respective doses of cypermethrin 0, 0.4, 1.8 and 8.0 mg/kg body weight and of methylparathion 0, 0.0115, 0.0518 and 0.2300 mg/kg body weight. The control group received vehicle solvent only. All groups were force-fed every two days for 30 days with these dose combinations. Body weight gain and organ weights were determined. Serum levels of IgG and IgA, reproductive hormones (luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and testosterone), as well as the thyroid hormones (triiodothyronine (T3), tetraiodothyronine (T4), and thyroid stimulating hormone (TSH) were measured using radioimmunoassay (RIA). In addition, two immunological parameters (rate of neutrophil phagocytosis, rate of lymphocyte transformation) were being measured in blood samples. RESULTS: The body weight gains were similar in all 4 groups. The weights of adrenal glands in exposed rats were heavier than those in control (P < 0.05). Serum FSH and E2 levels in exposed rats were higher than those in the control group (P < 0.01). Serum TSH levels were proportionally increasing with higher pesticide doses (r(s) = 0.329, P < 0.01). Lymphocyte transformation rates in all exposed animals were lower than that of the control group (P < 0.01). To the contrary, rates of neutrophil phagocytosis in all exposure groups were higher than those of the control group (P < 0.01). Furthermore, serum IgG levels of all exposed animals were lower than that of the control (P < 0.01) and serum IgA levels in exposed females were higher than that of the control (P < 0.01). Dose-response relationships for these changes were significant (rank correlation statistics P < 0.05 or < 0.01). CONCLUSION: Our results showed that exposure to different mixtures of cypermethrin and methyl parathion disrupted the endocrine hormone levels, and immune functions in rats.

[Effects of mixed cypermethrin and methylparathion on endocrine hormone levels and immune functions in rats: II. Interaction].

OBJECTIVE: To study interaction of mixed pesticides cypermethrin and methyl parathion on reproductive hormones, thyroid hormones, and immune functions in rats. METHODS: Eighty 2-month old Wistar rats (40 male and 40 female) were divided randomly by body weight into 8 groups. The dose 1/30 LD50 were chosen for the single or combined exposure representing respective doses of 0, cypermethrin 8.0 mg/kg bw, methylparathion 0.23 mg/kg bw, and 1/30 LD50 cypermethrin plus 1/30 LD50 methylparathion. The control group received vehicle solvent only. All groups were force-fed every two days for 30 days. Body weight gain and organ weights were determined. Serum levels of IgG and IgA, reproductive hormones [luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and testosterone], as well as the thyroid hormones [triiodothyronine (T3), tetraiodothyronine (T4), and thyroid stimulating hormone (TSH) were measured using radioimmunoassay (RIA). In addition, two immunological parameters (rate of neutrophil phagocytosis, rate of lymphocyte transformation] were being measured in blood samples. RESULTS: The most of index indicated addictive interaction, while the effects on relative weights of ovaries and adrenals, IgA and rate of lymphocyte transformation were antagonistic. It was of interest that the effect on estradiol was synergistic interaction in female rats, whereas it was addictive interaction in male rats, whose estradiol level could be increased 64.64% by cypermethrin exposure. CONCLUSION: Our results showed that exposure to cypermethrin and methyl parathion mixture at 1/30 LD50 dose had interaction on endocrine hormone levels, and immune functions in rats. Estradiol was very sensitive, the mixture can enhance estradiol level both in male and female rats.

[Experimental and clinical study on treatment of hypertrophic scars with (90)Sr radiation].

OBJECTIVE: To analyze the potential mechanism of preventive and therapeutic effects of (90)Sr on hypertrophic scar, and to observe its clinical effect. METHODS: Fibroblasts isolated from human hypertrophic scar were cultured in vitro and radiated by (90)Sr with the dose varying from 0 Gy (control group) to 5 Gy (LD group), 10 Gy (MD group), and 15 Gy (HD group). The cell cycle and apoptosis rate were determined by flow cytometry at post radiation hour (PRH) 24, 48, and 72. The concentration of type I collagen in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Therapeutic effects of (90)Sr radiation were evaluated among 348 patients with hypertrophic scars, 40 patients with keloids, and 114 patients for scar prevention after surgical operation. The number of fibroblasts after HE staining was compared among normal skin tissue, hypertrophic scar, and hypertrophic scar treated with (90)Sr radiation. Data were processed with one-way analysis of variance and q test. RESULTS: (1) Apoptotic rates in MD and HD groups at PRH 48 were higher than those at PRH 24, and the apoptotic rate was similar between MD group and HD group at PRH 72. Apoptotic rate in LD group at PRH 48 was significantly higher than that at PRH 24, but it decreased rapidly at PRH 72, which was significantly lower than those in MD and HD groups (with F values all equal to 916.711, P values all below 0.01). (2) At PRH 24, cell ratios of each phase in LD and HD groups were similar, and cell ratio of S phase in HD group [(48.1 ± 1.0)%] was higher than those in the other three groups (with F values all equal to 200.277, P values all below 0.01). At PRH 72, cell ratio of S phase in MD and HD groups was respectively (85.7 ± 5.2)%, (73.0 ± 8.4)%, implying that cells were blocked in S phase, and the values were all higher than those in control and LD groups (with F values all equal to 111.105, P values all below 0.01). (3) At the same time point, the concentration of type I collagen decreased along with the increase of radiation dose (with F values from 5044.449 to 8234.432, P values all below 0.01). With the same radiation dose, the concentration of type I collagen increased along with prolongation of time (with F values from 333.395 to 2973.730, P values all below 0.01). (4) Clinical observation showed the (obvious) effective rate of radiation for pathological scars and that for scar prevention after surgical operation added up to 88.45%. The number of fibroblasts per 200 times visual field in patients after (90)Sr radiation (86 ± 20) was less than that in patients without treatment [(198 ± 65), F = 208.405, P < 0.05]. CONCLUSIONS: The effect of (90)Sr radiation on fibroblasts and extracellular matrix can contribute to inhibition of scar formation, and the clinical effect is significant.

[Study on the mechanism of protective effect of oral L-arginine on intestine after scald injury in rats].

OBJECTIVE: To explore the mechanism of protective effect of oral L-arginine (L-Arg) on the intestine after scald injury in rats. METHODS: Sixty-six Sprague-Dawley (SD) rats were randomly divided into three groups: i.e. normal control (N, n = 6, without treatment), oral L-arginine group (A, n = 30, with 1 ml 70 g/L of L-Arg per os 2 times a day from 2 post scald hour (PSH)) on with normal enteral feeding and group B (n = 30, with oral feeding of cold boiled water after scald). The changes in the content of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), endothelin (ET), ET/NO ratio in the intestine and the level of plasma endotoxin (LPS) in portal vein were assessed at 6, 12, 24, 48, 72 PSH. Ileum tissue samples were harvested for pathological examination. RESULTS: The ET content in the intestinal tissue in A group at 6, 12 and 24 PSH (0.80 +/- 0.26 ng/g, 0.75 +/- 0.30 ng/g, 0.63 +/- 0.22 ng/g) was obviously lower than that in B group (1.26 +/- 0.38 ng/g, 1.34 +/- 0.37 ng/g, 0.97 +/- 0.19 ng/g, P < 0.05), but the NO contents in the intestine in A group at the same time points were significantly higher than that in B group (P < 0.01). The ET/NO ratio and the level of plasma endotoxin in A group were significantly lower than those in B group at each time point (P < 0.05 or 0.01). Pathological examination showed that the intestinal mucosal injury in the A group was obviously milder than that in the B group. CONCLUSION: Oral L-arginine was shown to have the effects to ameliorate ischemia reperfusion injury of the intestine and to protect the barrier function of the intestinal mucosa. This might be related to an increase in the NO level in intestinal mucosa resulting in maintenance of a stable ET/NO ratio.