Improved Diagnostic Accuracy of Multi-Slice Spiral CT Combined with MRI in Colon Cancer Patients with Ileus: A Comparative Study.

Background: Colon cancer is a common malignant tumor that often leads to intestinal obstruction, resulting in significant morbidity and mortality. Early and accurate diagnosis of colon cancer and associated ileus is crucial for timely treatment and improved patient outcomes. Various diagnostic methods, including MSCT and MRI, are currently used in clinical practice. However, the optimal imaging approach for accurate diagnosis remains uncertain. Objective: To study the value and accuracy of multi-slice spiral CT (MSCT) combined with magnetic resonance imaging (MRI) in diagnosing colon cancer obstruction. Methods: A retrospective analysis was performed on 100 cases of colon cancer and ileus patients admitted to the Hai'an Hospital of Chinese Medicine from January 2019 to July 2020. The cases were randomly divided into control and experimental groups, with 50 cases in each. The control group was diagnosed with MSCT, and the experimental group was diagnosed with MRI based on the control group. The positive and negative detection rates, test accuracy, sensitivity, and specificity were compared between the 2 groups. The area under the curve (AUC), quality of life (QOL) score, and mental status scale in non-psychiatric settings (MSSNS) score were calculated with the receiver operator characteristic curve (ROC) and compared between the 2 groups. Results: The test accuracy, positive detection rate, negative detection rate, test specificity, sensitivity, and AUC of the experimental group were significantly higher than those of the control group, and the results were statistically significant (P < .05). There was no significant difference in the QOL and the MSSNS scores between the 2 groups (P > .05). Conclusion: MSCT combined with MRI has a high application value in diagnosing colon cancer obstruction patients, and can significantly improve the test's accuracy, specificity and sensitivity.

Yi-qi-hua-yu-jie-du decoction induces ferroptosis in cisplatin-resistant gastric cancer via the AKT/GSK3ß/NRF2/GPX4 axis.

BACKGROUND: Resistance to chemotherapy in gastric cancer (GC) is a ubiquitous challenge for its treatment. Yi-qi-hua-yu-jie-du decoction (YJD), an empirical formula in Traditional Chinese Medicine (TCM), demonstrated survival-prolonging functions in patients with GC. Previous research has shown that YJD could also inhibit drug resistance in GC. However, the precise mechanisms for how YJD accomplishes this remain incompletely explained. PURPOSE: The research aimed to identify differential metabolic characteristics in cisplatin-resistant GC and investigate whether YJD can target these differences to suppress GC drug resistance. METHODS: Metabolomic analysis was conducted to identify metabolic disparities between cisplatin-resistant and parental GC cells, as well as metabolic modifications resulting from YJD intervention in cisplatin-resistant GC cells. The effect of YJD on ferroptosis stimulation was assessed by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), iron ions, the reduced glutathione (GSH) to oxidised glutathione (GSSG) ratio, and alterations in mitochondrial morphology. Western blotting and quantitative real-time polymerase chain reaction (Q-PCR) were employed to verity the mechanisms of YJD-triggered ferroptosis through GPX4 and NRF2 overexpression models, alongside the AKT activator SC79. In vivo validation was conducted using nude mouse xenograft models. RESULTS: Cisplatin-resistant GC exhibited altered GSH/GPX4 metabolism, and ferroptosis was a significantly enriched cell death pattern with YJD treatment in cisplatin-resistant GC cells. Ferroptosis biomarkers, including ROS, MDA, iron ions, the GSH/GSSG ratio, and mitochondrial morphology, were remarkably changed with the YJD intervention. Mechanistic experiments demonstrated that YJD inhibited the phosphorylation cascade activity of the AKT/GSK3ß pathway, thereby reducing NRF2 expression. The level of GPX4, a crucial enzyme involved in glutathione metabolism, was attenuated, facilitating ferroptosis induction in cisplatin-resistant GC. CONCLUSION: The research reveals, for the first time, changes in GSH/GPX4 metabolism in cisplatin-resistant GC cells based on metabolomic analysis. YJD induced ferroptosis in cisplatin-resistant GC by inhibiting GPX4 through the AKT/GSK3ß/NRF2 pathway, thus attenuating the cisplatin drug resistance in GC. Our findings identify metabolic changes in cisplatin-resistant GC and establish a theoretical framework for YJD on tackling drug resistance in GC through ferroptosis.

Sesquiterpenoids from the leaves of Sarcandra glabra.

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 µmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.

Lignans with (N, N-diethyl)methyl amino group from Buxus rugulosa.

Buxrugulosides A-E, four lignan glycosides (1-4) and a protocatechuate derivative (5) featuring a rare (N, N-diethyl)methyl amino group at aromatic rings, were obtained from the aerial parts of Buxus rugulosa, which is famous for treating coronary heart disease. Their structures including absolute configurations were elucidated by HRMS, 1D and 2D NMR, and by comparing their CD data with previous reports. Compound 1 was a rare sesquilignan, and all of these compounds were the first example of lignans with (N, N-diethyl)methyl amino group.

Chisosiamens A-E, five new ring-intact limonoids with isomerized furan ring from the fruit of Chisocheton siamensis.

Five new ring-intact limonoids with isomerized furan ring, chisosiamens A-E (1-5), along with four known compounds (6-9) were isolated from the fruit of Chisocheton siamensis Craib. Their structures were elucidated based on 1D and 2D NMR spectroscopic data, HRESIMS, circular dichroism, and exciton chirality method. The biological activities screening showed that new limonoid 5 exhibited significant NO inhibitory activity in LPS-activated RAW 264.7 macrophages (IC50: 10.13 ± 1.40 µM) and 1, 2, 5, and 9 effectively reversed the resistance in MCF-7/DOX cells with the range IC50 values of 10.20-15.06 µM (RI: 4.05-5.98).

Shizukaol A exerts anti-inflammatory effect by regulating HMGB1/Nrf2/HO-1 pathway.

BACKGROUND: Sarcandra glabra (Thunb.) Makino (Chloranthaceae) has a long history of being used in Traditional Chinese medicines (TCMs) to treat painful joints, fractures, arthritis, and other diseases caused by inflammation. It has been reported that lindenane-type sesquiterpenoid dimers are main anti-inflammatory ingredient of S. glabra. Meanwhile, shizukaol A, the precursor of these sesquiterpene dimers, possesses a good inhibitory effect on nitric oxide (NO) in our previous study. But its anti-inflammatory mechanism is still unclear. PURPOSE: This study aimed to explore the possible anti-inflammatory mechanism and potential targets of shizukaol A in lipopolysaccharide (LPS)-induced RAW 264.7 cells. METHODS: The release of NO and inflammatory cytokines in LPS-stimulated RAW 264.7 cells were measured by Griess reagent and ELISA, respectively. The relevant proteins including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) p65, High mobility group box 1 (HMGB1) were detected by western blot. Nuclear translocation of p65, HMGB1 and nuclear factor E2-related factor 2 (Nrf2) were examined by immunofluorescence. The level of reactive oxygen species (ROS) was tested by flow cytometry. The target of shizukaol A was investigated by molecular docking and Drug Affinity Responsive Target Stability (DARTS). RESULTS: Shizukaol A had a good inhibitory effect on NO with half maximal inhibitory concentration (IC50) of 13.79 ± 1.11 µM. Shizukaol A could down-regulate the expression of iNOS and COX-2. Further studies demonstrated that shizukaol A can significantly inhibit phosphorylation and nuclear translocation of NF-κB. Meanwhile, shizukaol A decreased the level of ROS and enhanced the expression of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Furthermore, shizukaol A up-regulated the expression of Nrf2 and its nuclear translocation. More importantly, shizukaol A could inhibit activation of HMGB1 by targeting HMGB1. CONCLUSION: Shizukaol A inhibited inflammation by targeting HMGB1 to regulate the Nrf2/HO-1 signaling pathway. Thus, shizukaol A may be an attractive therapeutic candidate for inflammatory diseases.

Stigmastane-type steroid saponins from the leaves of Vernonia amygdalina Del.

Vernoramyosides A-F (1-6), six new Δ7,9(11) stigmastane-type steroid saponins, along with four known analogues (7-10) were isolated from the leaves of Vernonia amygdalina Delile (Compositae). Their structures were determined by the combination of NMR, ECD and HR-ESI-MS data. These compounds all possessed highly oxidized side chain and a γ-lactam or α,ß-unsaturated five-membered lactone ring. All isolates were screened for their activities in reversing resistance in MCF/DOX cells.

Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats.

Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague-Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 µg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 µg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation.

Berberine reduces rat intestinal tight junction injury induced by ischemia-reperfusion associated with the suppression of inducible nitric oxide synthesis.

Berberine (BBR) has been shown to attenuate the deleterious effects of ischemia/reperfusion (I/R) injury in the brain. We evaluated the effects of BBR on intestinal tight junction (TJ) changes during mesenteric I/R. I/R was induced in rats by the occlusion of the superior mesenteric artery and reperfusion. The rats were randomized into four groups: control, BBR, I/R, and I/R + BBR. Intestinal permeability was determined by the lactulose/mannitol test. The ileum and colon were harvested to assess mucosal injury and inducible nitric oxide synthase activity. The TJ ultrastructure was studied by transmission electron microscopy. The expressions and locations of the TJ proteins, occludin and ZO-1, in the epithelium were investigated by immunofluorescence microscopy. We also used Western blot analysis to detect the distribution of TJ proteins in lipid raft fractions. Our results suggest that I/R-induced intestinal TJ dysfunction can be improved by BBR, thereby demonstrating the therapeutic potential of BBR for intestinal I/R.

The impact of perioperative glutamine-supplemented parenteral nutrition on outcomes of patients undergoing abdominal surgery: a meta-analysis of randomized clinical trials.

The objective of this study was to evaluate the impact of perioperative glutamine-supplemented parenteral nutrition (GLN-PN) on clinical outcomes in patients undergoing abdominal surgery. MEDLINE, EMBASE, and the Cochrane Controlled Clinical Trials Register were searched to retrieve the eligible studies. Eligible studies were randomized controlled trials (RCTs) that compared the effect of GLN-PN and standard PN on clinical outcomes in patients undergoing abdominal surgery. Clinical outcomes of interest were postoperative mortality, length of hospital stay, morbidity of infectious complication, and cumulative nitrogen balance. Statistical analysis was conducted by RevMan 5.0 software from the Cochrane Collaboration. Sixteen RCTs with 773 patients were included in this meta-analysis. The results showed a significant decrease in the infectious complication rates of patients undergoing abdominal surgery receiving GLN-PN (risk ratio [RR], 0.48; 95% confidence interval [CI], 0.32 to 0.72; P = 0.0004). The overall effect indicated glutamine significantly reduced the length of hospital stay in the form of alanyl-glutamine (weighted mean difference [WMD], -3.17; 95% CI, -5.51 to -0.82; P = 0.008) and in the form of glycyl-glutamine (WMD, -3.40; 95% CI, -5.82 to -0.97; P = 0.006). A positive effect in improving postoperative cumulative nitrogen balance was observed between groups (WMD, 7.40; 95% CI, 3.16 to 11.63; P = 0.0006), but no mortality (RR, 1.52; 95% CI, 0.21 to 11.9; P = 0.68). Perioperative GLN-PN is effective and safe to shorten the length of hospital stay, reduce the morbidity of postoperative infectious complications, and improve nitrogen balance in patients undergoing abdominal surgery.

The reduction of allograft arteriosclerosis in intestinal transplant is associated with sphingosine kinase 1/sphingosine-1-phosphate signaling after fish oil treatment.

BACKGROUND: Transplant arteriosclerosis is a major cause of late intestinal allograft dysfunction. However, little is known about the immunologic and molecular mechanisms underlying it, and no effective treatment is available. This study aimed to investigate the role of sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P) in transplant arteriosclerosis and find out whether fish oil (FO) attenuates allograft arteriosclerosis through S1P signaling. METHODS: A rat model with orthotopic intestinal transplantation was conducted in this study. Animals received daily FO supplementation after intestinal transplant. The allogeneic recipients by phosphate-buffered saline or corn oil treatment served as controls. The allograft arteriosclerosis was characterized, and the expression of SPHK1 and S1P receptors (S1P1, S1P2, and S1P3) was determined on day 190 posttransplant. RESULTS: The allogeneic controls presented transplant vasculopathy in mesenteric vessels, including intimal thickening, fibrosis, and leukocyte infiltration. The transplant arteriosclerosis was markedly reduced in FO-fed animals. The pression of SPHK1 and its activity were significantly augmented, and the expression of S1P1 and S1P3 messenger RNA was up-regulated in the allogeneic controls. FO supplementation suppressed the activation of SPHK1 and led to a decrease in the expression of S1P1 and S1P3 in these tissues in transplant arteriosclerosis. CONCLUSIONS: These results demonstrate that the activation of SPHK1/S1P signaling plays a possible role in the pathogenesis of transplant arteriosclerosis. The reduction of allograft arteriosclerosis by FO may be associated with down-regulation of SPHK1/S1P signaling. Understanding the role of FO for SPHK1/S1P may help us to identify considerable therapeutic targets for transplant arteriosclerosis.

Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

BACKGROUND: The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

Berberine hydrochloride attenuates cyclooxygenase-2 expression in rat small intestinal mucosa during acute endotoxemia.

The effect of berberine hydrochloride (BBR) on inducible cyclooxygenase-2 (COX-2) in small intestinal mucosa and related mechanisms was investigated in a rat model of acute endotoxemia. The results showed that lipopolysaccharide (LPS) increased COX-2 expression, whereas SB202190 and BBR curtailed it. LPS increased phosphorylation of mucosal p38 MAPK and ATF2 as well as production of ATF2, whereas BBR attenuated these effects. LPS upregulated mucosal peroxisome proliferator-activated receptor gamma (PPARγ), but BBR reduced this receptor. GW9662 aggravated LPS-induced and reversed BBR-attenuated COX-2 expression. The findings showed that BBR ameliorated COX-2 overexpression partially via modulation of p38 and PPARγ pathways during acute endotoxemia.

Berberine attenuates lipopolysaccharide-induced impairments of intestinal glutamine transport and glutaminase activity in rat.

Berberine was reported to protect against the intestinal injury and improve the survival rate in sepsis, and glutamine deficiency was considered to be correlated with mortality in sepsis. We found that berberine pretreatment ameliorated lipopolysaccharide-induced direct intestinal injury and mucosal hypoplasia and attenuated impairments of intestinal glutamine transport and glutaminase activity, B(0)AT1 mRNA and protein expressions, and glutaminase protein expression. These findings showed the first time that berberine pretreatment could improve intestinal recovery and attenuate the impairment of glutamine transport and glutaminase activity in rat sepsis. This might be one of the mechanisms for the beneficial effect of berberine on sepsis.

The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells.

Berberine is one of the main alkaloids of Rhizoma coptidis which has been used for patients with gastrointestinal disorders. The major aim of this study was to investigate the effect of berberine on tight junction. Caco-2 cells were treated with various concentration of berberine. We observed the integrity of tight junction by measuring the transepithelial electrical resistance (TEER), and also studied the effect of berberine on morphology of tight junction and tight junction protein. These findings showed the first time that berberine could reduce epithelial gut permeability, and might help explain the possible mechanisms of anti-diarrhea activity of berberine.

Long-term n-3 polyunsaturated fatty acids administration ameliorates arteriosclerosis by modulating T-cell activity in a rat model of small intestine transplantation.

BACKGROUND: Fish oil, rich in n-3 polyunsaturated fatty acids (n-3 PUFAs), has been found to reduce graft rejection and increase allografts survival. But these studies mainly focused on acute rejection. We imitated long-term fish oil administration to investigate the effects of n-3 PUFAs on graft arteriosclerosis, and T cells in a rat model of small intestine transplantation. METHODS: From 2 weeks pre-transplantation to the 60th day post-transplantation, the Lewis rats were supplemented by gavage with phosphate buffer saline, corn oil and fish oil respectively. Total small intestine was heterotopically transplanted from F344 to Lewis rat. Graft arteriosclerosis was assessed by histological grading of intimal thickening. The expression of CD25 and CD154, IL-2 level, and NF-kappaB activation in T cells were analyzed by western blotting, ELISA, and electrophoretic mobility shift assay respectively. RESULTS: Compared with corn oil, graft arteriosclerosis was ameliorated by fish oil significantly. The expression of CD25 and CD154, IL-2 level, and NF-kappaB activation were markedly reduced by fish oil. CONCLUSIONS: Long-term n-3 PUFAs administration pre- and post-transplantation could inhibit T-cell activity by reducing CD154 expression and NF-kappaB activation, which might contribute to amelioration of graft arteriosclerosis.