Predictive value of combining urinary N-acetyl-ß-D-glucosaminidase and serum homocysteine for contrast-induced nephropathy in patients after percutaneous coronary intervention.

Background: Contrast-induced nephropathy (CIN) can lead to serious complications following percutaneous coronary intervention (PCI). Urine N-Acetyl-ß-D-glucosaminidase (uNAG) and serum homocysteine (sHCY) are both potential predictors for CIN detection, but their combination has not been explored. We aimed to combine uNAG and sHCY as predictors for the early detection of CIN and for prognosis prediction in patients after PCI. Methods: A total of 232 consecutive patients who underwent PCI at a university hospital were recruited for this study. According to the European Society of Urology and Reproduction (ESUR) criterion, CIN is defined as an elevation of serum creatinine (sCr) by ≥25% or ≥0.5 mg/dl from baseline within 48 h. We assessed the use of individual biomarkers (uNAG and sHCY) measured around PCI and their combinations for CIN detection and prognosis prediction. Receiver operating characteristic curves (ROC) and area under the curve (AUC) were used to evaluate the predictive efficiency of potential predictors. Results: In total, 54 (23.28%) patients developed CIN. Concentrations of uNAG and sHCY increased significantly in CIN subjects (p < 0.05) than non-CIN. CIN could be predicted by uNAG and sHCY but not by creatinine at an early stage. At pre-PCI, 0, 12, 24, and 48 h after PCI, the AUC-ROC value of uNAG in calculating total CIN was 0.594, 0.603, 0.685, 0.657, and 0.648, respectively. The AUC-ROC value of sHCY in calculating total CIN was 0.685, 0.726, 0.771, 0.755, and 0.821, respectively. The panel of uNAG plus sHCY detected CIN with significantly higher accuracy than either individual biomarker alone and earlier than sCr. For detecting total CIN, this panel yielded AUC-ROCs of 0.693, 0.754, 0.826, 0.796, and 0.844 at pre-PCI, 0, 12, 24, and 48 h after PCI, respectively, which were superior to those of the individual biomarkers. For predicting the incidence of major adverse cardiovascular events (MACE) within 30 days to 12 months, the AUC-ROC values for uNAG and sHCY measured before discharge were 0.637 and 0.826, respectively. The combined panel yielded an AUC-ROC of 0.832. The combined detection did not significantly enhance the predictive capability for MACE in patients with CIN. The CIN group and the non-CIN group showed no significant difference in the Coronary Heart Disease Intensive Care Unit (CCU) stay time, hospital stay time, demand for renal replacement therapy, CCU mortality rate, and in-hospital mortality rate. Conclusions: The uNAG and sHCY panel demonstrated better sensitivity and specificity for predicting the diagnosis and prognosis of CIN in patients after PCI, earlier than sCr. The combination of these biomarkers revealed a significantly superior discriminative performance for CIN detection and prognosis compared to using uNAG or sHCY alone.

Excitatory purinergic and cholinergic expression changed in a partial bladder outlet obstruction-induced overactive bladder rat model.

Overactive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin-eosin (H&E) and Masson's trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression.

Microbial cell wall sorption and Fe-Mn binding in rhizosphere contribute to the obstruction of cadmium from soil to rice.

Screening high-tolerant microorganisms to cadmium (Cd) and revealing their bio-obstruction mechanism could be significant for Cd regulation from farmland to the food chain. We examined the tolerance and bio-removal efficiency of Cd ions of two bacterial strains, Pseudomonas putida 23483 and Bacillus sp. GY16, and measured the accumulation of Cd ions in rice tissues and its different chemical forms in soil. The results showed that the two strains had high tolerance to Cd, but the removal efficiency was decreased successively with increasing Cd concentrations (0.05 to 5 mg kg-1). Cell-sorption accounted for the major proportion of Cd removal compared with excreta binding in both strains, which was conformed to the pseudo-second-order kinetics. At the subcellular level, Cd was mostly taken up by the cell mantle and cell wall, and only a small amount entered into the cytomembrane and cytoplasmic with time progressed (0 to 24 h) in each concentration. The cell mantle and cell wall sorption decreased with increasing Cd concentration, especially in the cytomembrane and cytoplasmic. The scanning electron microscope (SEM) and energy dispersive X-ray (EDS) analysis verified that Cd ions were attached to the cell surface, and the functional groups of C-H, C-N, C=O, N-H, and O-H in the cell surface may participate in cell-sorption process tested by the FTIR analysis. Furthermore, inoculation of the two strains significantly decreased Cd accumulation in rice straw and grain but increased in the root, increased Cd enrichment ratio in root from soil, decreased Cd translocation ratio from root to straw and grain, and increased the Cd concentrations of Fe-Mn binding form and residual form in rhizosphere soil. This study highlights that the two strains mainly removed Cd ions in solution through biosorption and passivated soil Cd as Fe-Mn combined form ascribe to its characteristics of manganese-oxidizing, eventually achieving bio-obstruction of Cd from soil to rice grain.

Effects of NBP on postoperative cognitive dysfunction in rats via Nrf 2/ARE pathway.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a common postoperative disease that threatens patients' quality of life, especially elderly patients. With the popularity of anesthesia/surgery, POCD has received more attention worldwide. The objective of this research is to evaluate 3-n-Butylphthalide (NBP)'s protective effect on postoperative cognitive function in rats and its related mechanisms. METHODS: Tibial fracture models of senile rats of POCD were established and divided into blank control group, solvent group, NBP group, Nrf 2 agonist group, and Nrf 2 inhibitor group. The changes in the cognitive abilities of rats were systematically evaluated by the Morris water maze test. After hematoxylin-eosin (HE) staining of the hippocampus, the morphological and structural changes of hippocampal neurons were observed by light microscopy. The expressions of apoptosis-related proteins were analyzed by immunohistochemistry and Western blot was used to detect the expressions of Nrf 2,HO-1,Mfn1,Mfn2,Drp1 proteins. Moreover, the changes in the morphology of mitochondria were observed by transmission electron microscopy. RESULTS: Through the water maze test, we observed that the incidence of postoperative cognitive impairment in the NBP, agonist, and inhibitor groups was substantially lower as compared to the blank control group and solvent group (P < 0.05). The expressions of Nrf 2, HO-1, Mfn1, Mfn2, and Drp1 proteins in the NBP group were upregulated in comparison to the blank control group and the solvent group. The expressions of related proteins in the inhibitor group were substantially lower in comparison to the NBP group. CONCLUSIONS: NBP can affect the postoperative cognitive function of rats by activating the Nrf 2/ARE signaling pathway.

Modified Cangfu Daotan decoction ameliorates polycystic ovary syndrome with insulin resistance via NF-κB/LCN-2 signaling pathway in inflammatory microenvironment.

This study explored the possible connection between the insulin resistance-targeting protein adipokine lipocalin-2 (LCN-2) and NF-κB signaling pathway in the inflammatory microenvironment in PCOS-IR model rats to determine the pharmacological mechanism of modified Cangfu Daotan decoction (MCDD) intervention for PCOS-IR. We used a high-fat diet (42 days) combined with letrozole (1 mg/kg/day, 42 days) to establish a PCOS-IR rat model. From the third week after modeling, the rats were given continuous administration of MCDD (high dose with 31.68 g/kg, medium dose with 15.84 g/kg, and low dose with 7.92 g/kg) for 28 days. Serum, ovarian tissue, liver, and adipose tissue were collected after the last gavage. Enzyme-linked immunosorbent assay, hematoxylin-eosin (HE) staining, Masson staining, qRT-PCR, and Western blot experiments were performed to detect various indicators. Our results showed that MCDD could reduce body weight and abdominal fat weight; restore normal estrous cycle and ovarian function; alleviate fatty liver; regulate HOMA-IR and OGTT index; reduce serum inflammatory factor levels, LCN-2 level, and gene expression; and regulate the insulin signal transduction and NF-κB pathways in PCOS-IR rats. Thus, MCDD may play a role in improving ovarian function in PCOS-IR rats by downregulating NF-κB/LCN-2 proteins and upregulating the gene expression of Insr/Irs-1/Glut4 in the insulin signaling pathway in the inflammatory environment.

PROTACs in gastrointestinal cancers.

Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.

The Effects of Patchouli Alcohol on Diarrhea-Predominant Irritable Bowel Syndrome are Correlated with Phenotypic Plasticity in Myenteric Neurons and the Targeted Regulation of Myosin Va.

Patchouli alcohol (PA) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine, and the related mechanism remains to be fully understood. Our previous study has indicated that PA significantly reduced visceral sensitivity and defecation area in IBS-D rats. In this study, we prepared an IBS-D rat model and observed the dynamic intestinal motility and colonic longitudinal muscle and myenteric plexus (LMMP) neurons, as well as their subtypes at D14, D21, and D28. After PA administration, we observed the effects on the changes in intestinal motility, colonic LMMP neurons, and LMMP Myosin Va in IBS-D rats and their co-localization with inhibitory neurotransmitter-related proteins. The results indicated that PA treatment could alleviate IBS-D symptoms, regulate the abnormal expression of LMMP neurons, increase Myosin Va expression, up-regulate co-localization levels of Myosin Va with neuronal nitric oxide synthase (nNOS), and promote co-localization levels of Myosin Va with vasoactive intestinal polypeptide (VIP). In conclusion, this study demonstrated the neuropathic alterations in the colon of chronic restraint stress-induced IBS-D rat model. PA reversed the neuropathological alteration by affecting the transport process of nNOS and VIP vesicles via Myosin Va and the function of LMMP inhibitory neurons, and these effects were related to the mechanism of enteric nervous system (ENS) remodeling.

Suo Quan Wan ameliorates bladder overactivity and regulates neurotransmission via regulating Myosin Va protein expression.

BACKGROUND: Ancient prescriptions of Suo Quan Wan (SQW) have therapeutic effects on diabetic bladder dysfunction. However, the underlying mechanism remains unclear. Here, we hypothesized that SQW ameliorates bladder overactivity and regulates neurotransmission via regulating Myosin Va protein expression. METHODS: After diabetic rats were induced by streptozotocin (65 mg/kg), the model of diabetic bladder dysfunction was established by detecting fasting blood glucose, urodynamic test, in vitro muscle strip experiments, and histological examination. One week after induction, SQW was given to observe the therapeutic effect. The expression levels of Myosin Va in control, Model, SQW L and SQW H groups were detected by RT-qPCR, RNAscope and immunofluorescence assay. The expression levels of ChAT, SP, nNOS and VIP proteins were observed by immunofluorescence assay. After knockdown and overexpression of Myosin Va, the expression changes of ChAT, SP, nNOS and VIP and the regulatory role of SQW were observed. RESULTS: STZ-induced DM rats had significantly higher serum glucose levels and lower body weight. Compared with the diabetic rats, SQW treatment significantly improved urination function with decreased residual volume (RV), bladder compliance (BC), non-voiding contractions (NVCs), and increased voided efficiency (VE). In addition, contractile responses of muscle strips to electrical-field stimulation (EFS), carbachol (CCh), KCl were significantly lower in the SQW H and SQW L groups than those in the model group. RT-qPCR found that the expression of Myosin Va in the bladder tissue or bladder neurons in model group was significantly increased compared with the control group, and SQW treatment significantly decreased the levels of Myosin Va. In DM rats, ChAT and SP expression were significantly increased, while nNOS and VIP expression were significantly decreased, and SQW improved this phenomenon. Interestingly, SQW ameliorated the abnormal expression of ChAT, SP, nNOS and VIP caused by myosin Va knockdown, and Myosin Va overexpression results are consistent with these. CONCLUSIONS: SQW ameliorates overactive bladder and regulate neurotransmission via regulating Myosin Va mRNA and protein expression.

Low-Dose Cyclophosphamide Induces Nerve Injury and Functional Overactivity in the Urinary Bladder of Rats.

Aim: This research aimed to investigate the neurotoxicity of low-dose cyclophosphamide (CYP) on the urinary bladder of rats by in vivo and in vitro studies. Methods: To establish CYP-induced cystitis rat model, rats were treated with three intraperitoneal injections of CYP (25 mg/kg) in a week. During treatment, the up-down method was used to assess the mechanical withdrawal threshold. On day 8, urodynamic test and bladder smooth muscle contractility study, including the contraction of bladder strips to electrical field stimulation (EFS, 2-64 Hz), carbachol (CCh, 10-8-10-5 M) and KCl (120 mM), were performed to evaluate the function of bladder function. Body weight and bladder weight were also recorded. Morphometric analysis using an optical microscope and transmission electron microscope was performed to observe the changes of microstructure and submicrostructure of the bladder. The major pelvic neurons were isolated and treated with acrolein (the main CYP metabolite) to assess apoptosis in vitro. RT-PCR assays were used to quantify the mRNA expression levels of Nlrp6, Asc, Casp11 and Casp1 in bladder tissues and primary neurons. Results: After CYP injections, the body weights decreased, but the bladder weights increased in the model group. The mechanical withdrawal threshold of the cystitis model remained at a low level. The morphometric analysis suggested bladder inflammation and neuroinflammation in the bladder of the cystitis rat model. Urodynamic test revealed that, the amplitude, the pressure baseline, the peak pressure and pressure threshold of model rats significantly increased after CYP treatment. The muscle strips of model rats exhibited significantly higher contractility caused by EFS and CCh than the controls. Apoptotic cells appeared at the highest concentration group (100 µM acrolein) after 6 h of acrolein incubation in apoptosis assay of primary neurons. The mRNA expression levels of Nlrp6 and Casp11 were significantly increased in the cystitis rat model and in the acrolein-treated neurons. Conclusions: Low-dose CYP treatment was confirmed to induce nerve injury, which leading to bladder pain and overactive bladder in female rats, and the up-regulation of Nlrp6 and Casp11 may contribute to these pathological changes.

Clinical Strains of Helicobacter pylori With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy.

Helicobacter pylori was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of H. pylori activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular H. pylori and promotes its drug resistance. This study revealed that some clinical drug-resistant H. pylori strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from Pogostemon cablin (Blanco) Benth (Labiatae), showed reliable activity against intracellular H. pylori. The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by H. pylori, thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular H. pylori has great implications for clinical treatment, and PA can act against invasive H. pylori based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant H. pylori.

Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation.

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

[Spectral Distribution and Pollution Characteristics of Polybrominated Diphenyl Ethers in the Air of an Office Building Clustered Area].

To evaluate the pollution level, congener distribution, and human exposure of polybrominated diphenyl ethers (PBDEs) in the atmosphere of Beijing's office buildings, outdoor air samples (particles+gas) were collected from a typical scientific area and PBDEs concentrations were quantified using GC-MS. The results showed that the mass concentrations of PBDEs in the gas phase, PM2.5, and PM10 were 2.3-78.6 pg·m-3, 14.4-335.3 pg·m-3, and 11.6-431.7 pg·m-3, respectively, and the annual average mass concentrations were 21.7 pg·m-3, 96.9 pg·m-3, and 149.3 pg·m-3, respectively. BDE-209 was the predominant congener in particulates, accounting for 50% of the total concentration. The mass concentration of PBDEs in the particles decreased in the following order:autumn > winter > summer > spring, with an obvious change in winter and stability in summer. Tri-BDEs mainly existed in the gas phase, and the proportion of PBDEs in the particle phase increased with bromine number. Source analysis indicated that BDE-209 degradation was an important source of other PBDEs in the air. Exposure risk analysis showed that the respiratory intake of children and adults was 18.6 pg·(kg·d)-1 and 7.1 pg·(kg·d)-1, respectively, which is far below the recommended lowest observed adverse effect level of 1 mg·(kg·d)-1. Similarly, the carcinogenic risk values of BDE-209 for children and adults were 2.3×10-9 and 3.7×10-9, respectively, which were much smaller than the carcinogenic risk limit of 10-6, indicating that there was no health hazard from PBDEs in the atmosphere.

Codelivery of GRP78 siRNA and docetaxel via RGD-PEG-DSPE/DOPA/CaP nanoparticles for the treatment of castration-resistant prostate cancer.

Background: Castration-resistant prostate cancer (CRPC) accounts for the majority of prostate cancer deaths, and patients with CRPC are prone to developing drug resistance. Therefore, there is a need to develop effective therapeutics to treat CRPC, especially drug-resistant CRPC. Although various nanoparticles have been developed for drug or gene delivery and control release, approaches to reproducibly formulate the optimal treatment with nanoparticles that could effectively target CRPC and bone metastasis remain suboptimal. Recently, codelivery of a chemotherapeutic agent and a small interfering RNA (siRNA) has become a promising strategy for the treatment of drug-resistant prostate cancer. Methods: In a previous study, we prepared a novel RGD-PEG-DSPE/CaP nanoparticle as an effective and biocompatible drug and gene delivery system. In this study, we further modify the nanoparticle to obtain the LCP-RGD nanoparticle, which contains a calcium phosphate (CaP) core, dioleoyl phosphatidic acid (DOPA) and RGD modified poly(ethylene glycol)-conjugated distearoyl phosphatidylethanolamine (RGD-PEG-DSPE). This drug delivery system was used for codelivery of GRP78 siRNA and docetaxel (DTXL) for the treatment of the PC-3 CRPC. Results: The nanoparticles contain the CaP core, which can effectively compress the negatively charged siRNA, while the DOPA and RGD-PEG-DSPE component can effectively carry DTXL. The arginine-glycine-aspartic acid (RGD) segment can target the prostate cancer site, as the cancer site is neovascularized. This novel nanoparticle has good stability, excellent biocompatibility, high drug and siRNA loading capacity, and an in vitro sustainable release profile. Conclusion: Codelivery of DTXL and GRP78 siRNA has enhanced in vitro and in vivo anti-prostate cancer effects which are much greater than using free DTXL and free GRP78 siRNA together. Our study also indicated that codelivery of DTXL and GRP78 siRNA have an in vitro and in vivo combinational anti-prostate cancer effect and also could effectively sensitize the cell-killing effect of DTXL; this method may be especially suitable for drug-resistant CRPC treatment.

Time-dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin-induced diabetic mice.

AIM: Diabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). This study aimed to investigate the functional, structural, and molecular changes of the bladder at 0, 3, 6, 9, and 12 weeks after DM induction by streptozotocin (STZ) in male C57BL/6 mice. METHODS: Male C57BL/6J mice were injected with STZ (130 mg/kg). Then, diabetic general characteristics, cystometry test, histomorphometry, and contractile responses to α, ß-methylene ATP, KCl, electrical-field stimulation, carbachol were performed at 0, 3, 6, 9, and 12 weeks after induction. Finally, protein and messenger RNA (mRNA) expressions of myosin Va and SLC17A9 were quantified. RESULTS: DM mice exhibited lower body weight, voiding efficiency and higher water intake, urine production, fasting blood glucose, oral glucose tolerance test, bladder wall thickness, maximum bladder capacity, residual volume, bladder compliance. In particular, nonvoiding contractions has increased more than five times at 6 weeks. And the amplitudes of spontaneous activity, contractile responses to all stimulus was about two times higher at 6 weeks but cut almost in half at 12 weeks. The protein and mRNA expressions of myosin Va and SLC17A9 were about two times higher at 6 weeks, but myosin Va was reverted nearly 40% while SLC17A9 is still higher at 12 weeks. CONCLUSIONS: DBD transitioned from a compensated state to a decompensated state in STZ-induced DM mice at 9 to 12 weeks after DM induction. Our molecular data suggest that the transition may be closely related to the alterations of myosin Va and SLC17A9 expression levels in the bladder with time.

Unraveling the Novel Protective Effect of Patchouli Alcohol Against Helicobacter pylori-Induced Gastritis: Insights Into the Molecular Mechanism in vitro and in vivo.

Patchouli alcohol (PA), a natural tricyclic sesquiterpene extracted from Pogostemon cablin (Blanco) Benth. (Labiatae), has been found to exhibit anti-Helicobacter pylori and anti-inflammatory properties. In this study, we investigated the protective effect of PA against H. pylori-induced gastritis in vitro and in vivo, and determined the underlying mechanism. In the in vivo experiment, a C57BL/6 mouse model of gastritis was established using H. pylori SS1, and treatments with standard triple therapy or 5, 10, and 20 mg/kg PA were performed for 2 weeks. Results indicated that PA effectively attenuated oxidative stress by decreasing contents of intracellular reactive oxygen species (ROS) and malonyldialdehyde (MDA), and increasing levels of non-protein sulfhydryl (NP-SH), catalase and glutathione (GSH)/glutathione disulphide (GSSG). Additionally, treatment with PA significantly attenuated the secretions of interleukin 1 beta (IL-1ß), keratinocyte chemoattractant and interleukin 6 (IL-6). PA (20 mg/kg) significantly protected the gastric mucosa from H. pylori-induced damage. In the in vitro experiment, GES-1 cells were cocultured with H. pylori NCTC11637 at MOI = 100:1 and treated with different doses of PA (5, 10, and 20 µg/ml). Results indicated that PA not only significantly increased the cell viability and decreased cellular lactate dehydrogenase (LDH) leakage, but also markedly elevated the mitochondrial membrane potential and remarkably attenuated GES-1 cellular apoptosis, thereby protecting gastric epithelial cells against injuries caused by H. pylori. PA also inhibited the secretions of pro-inflammatory factors, such as monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-α (TNF-α) and IL-6. Furthermore, after PA treatment, the combination of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) and cysteine-aspartic proteases 1 (CASPASE-1), the expression levels of NLRP3 inflammasome-related proteins, such as thioredoxin-interacting protein (TXNIP), pro-CASPASE-1, cle-CASPASE-1, and NLRP3 and genes (NLRP3 and CASPASE1) were significantly decreased as compared to the model group. In conclusion, treatment with PA for 2 weeks exhibited highly efficient protective effect against H. pylori-induced gastritis and related damages. The underlying mechanism might involve antioxidant activity, inhibition of pro-inflammatory factor and regulation of NLRP3 inflammasome function. PA exerted anti-H. pylori and anti-gastritis effects and thus had the potential to be a promising candidate for treatment of H. pylori-related diseases.

Prognostic value of liver stiffness measurement for the liver-related surgical outcomes of patients under hepatic resection: A meta-analysis.

BACKGROUND: Previous studies have discussed the liver stiffness measurement (LSM) performance on predicting liver-related surgical outcomes for patients of hepatocellular carcinoma (HCC) under hepatic resection, yet there is much variation in reporting and consistency of findings. Therefore, we report a meta-analysis on this issue. METHODS: We comprehensively searched PubMed, Embase, and Web of science to find the eligible cohort studies. The pooled Odds Ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate effect. The weighted mean LSM value was calculated as the optimal LSM cut-off value among studies. RESULTS: 12 prospective cohort studies and one retrospective cohort study, including a total of 1942 cases were identified. The pooled results showed that preoperative LSM is significantly associated with the occurrence of overall postoperative complications (OR 1.76, 95% CI 1.46-2.11). In addition, a weighted mean LSM value of 14.2 kPa and 11.3KPa were suggested as the optimal LSM cut-off value reference using transient elastoqraphy (TE) for predicting overall postoperative complications in Asia countries and European countries, respectively. CONCLUSIONS: Preoperative LSM should be taken into account cautiously in the management of patients undergoing hepatectomy of HCC. Future studies could focus on setting a prognostic model integrated with LSM in predicting post-hepatectomy outcomes.

Knockdown of lncRNA CCAT2 inhibits endometrial cancer cells growth and metastasis via sponging miR-216b.

OBJECTIVE: Colon cancer-associated transcript 2 (CCAT2), a novel lncRNA has been reported as an oncogene in several cancers. This study was aimed to explore whether CCAT2 also exerted oncogenic roles in endometrial cancer cells. MATERIALS AND METHODS: The expression of CCAT2 in 30 pairs of endometrial cancer and matched non-cancerous tissues were detected by qRT-PCR. Two endometrial cancer cell lines HEC-1-A and RL95-2 were used throughout this study. CCAT2 in cells was silenced by transfection with shRNA targeted CCAT2, then cell growth and metastasis were assessed by performing trypan blue staining, Transwell assay, and flow cytometry. Dual-luciferase reporter assay was used to detect the combination of miR-216b and CCAT2. Besides, the expression of miR-216b and Bcl-2 in cells were overexpressed or suppressed by transfection with their correspondingly mimic/vector or inhibitor/shRNA. qRT-PCR and western blot analysis were performed to detect the expression of Bcl-2 and main factors in PTEN/PI3K/AKT and mTOR signaling pathways. RESULTS: CCAT2 was highly expressed in endometrial cancer tissues when compared to non-cancerous endometrial tissues. Knockdown of CCAT2 inhibited HEC-1-A and RL95-2 cells viability, migration, invasion, but induced apoptosis. CCAT2 was an endogenous sponge by competing for miR-216b, and miR-216b suppression alleviated CCAT2 silence-diminished cell growth and metastasis. miR-216b negatively regulated Bcl-2 and Bcl-2 could further active PTEN/PI3K/AKT and mTOR signaling pathways. CONCLUSIONS: To conclude, these results demonstrated lncRNA CCAT2 was highly expressed in endometrial cancer tissues. Knockdown of CCAT2 inhibited cell growth and metastasis of endometrial cancer cells by sponging miR-216b.

Tetrahydrocurcumin is more effective than curcumin in inducing the apoptosis of H22 cells via regulation of a mitochondrial apoptosis pathway in ascites tumor-bearing mice.

Curcumin (CUR), a widely used food additive, is derived mainly from Curcuma species that has been applied traditionally for the treatment of various diseases, including hepatocellular carcinoma (HCC). However, its poor systemic bioavailability hampers its clinical application, which may be related to its wide metabolism. Tetrahydrocurcumin (THC) is a major metabolite of CUR and has been reported to have multiple biologic activities. We investigated, for the first time, the efficacy and associated mechanism of action of THC and CUR in a H22 ascites tumor-bearing model in mice. THC evoked a significant dose-dependent promotion of survival and was significantly more effective than CUR in inhibiting tumor growth, including increased body weight, abdominal circumference, ascites volume, and the viability of cancer cells. Experiments on essential immune organs indicated that THC had a more favorable margin of safety than the reference drug cyclophosphamide. THC induced the apoptosis of H22 cells obviously by increasing the level of p53 and decreasing the level of murine double minute 2. THC also decreased the expression of Bcl-2 significantly and increased the expression of Bcl2-associated X, resulting in the release of cytochrome C. THC significantly activated and induced cleavage of caspase-3 and caspase-9 to induce the apoptosis of H22 cells. Taken together, these results indicate that THC was more effective than CUR in inhibiting the apoptosis of H22-induced ascites tumor cells and achieved it via regulation of a mitochondrial apoptosis pathway. THC might be a bioactive anti-tumor form of CUR and represented a potentially effective agent for HCC treatment.

Lymph node tuberculosis mimicking malignancy on 18F-FDG PET/CT in two patients: A case report.

18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) imaging, an established procedure for evaluation of malignancy, reports an increased 18F-FDG uptake in acute or chronic inflammatory condition. Lymph node tuberculosis (LNTB) is the most common form of extrapulmonary tuberculosis. However, the absence of clinical symptoms and bacteriological basis makes it difficult to diagnose. In the current case report, two patients with LNTB mimicking malignant lymphoma are presented by 18F-FDG PET/CT. The objective of the present report is to emphasize that LNTB should be considered as a noteworthy differential diagnosis in patients with enlarged lymph nodes, particularly in tuberculosis-endemic countries, and that lymph node biopsy serves a vital role in diagnosing LNTB.