[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

[miR-30a-5p promotes the apoptosis of chondrocytes in patients with osteoarthritis by targeting protein kinase B].

Objective: To investigate the expression of miR-30a-5p in cartilage of osteoarthritis patients, and to explore its mechanism of chondrocyte apoptosis. Methods: From May 2015 to December 2016, tissue specimen of 289 patients with osteoarthritis was collected in Department of Orthopedics, Changzhou traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine.The expression of miR-30a-5p and protein kinase B(Akt) mRNA in cartilage of different patients was detected by qPCR.The apoptosis of chondrocytes was detected by Tunel method.The expression of related proteins in tissues and cells was detected by immunoblotting, and apoptosis and cell cycle were detected by flow cytometry. Results: The expression of miR-30a-5p in OA patients was significantly higher than control patients (P<0.05), but Aktwas positively related[(3.64±0.95)vs(1.03±0.31), P<0.05]. The expression of miR-30a-5p in cartilage of OA patients was negatively correlated with Akt mRNA expression (r=0.729 3, P<0.001), but it had a positive correlation with the apoptotic rate (r=0.847 5, P<0.001). miR-30a-5p targets negative regulation of Akt gene expression in SW1353 cells, and the expression of p-Akt, IkB-α, p-IkB-α, p65, p-p65 and mTOR and p-mTOR were significantly down-regulated by miR-30a-5p (P<0.05). Compared with normal SW1353 cells, the apoptosis rate of SW1353 cells which was transfected with miR-30a-5p-mimics increased by 9.65 times, G0/G1 phase cells increased by 1.37 times, S phase cells decreased by 60.94%, G2/M phase cells decreased 19.53%. Conclusion: miR-30a-5p is highly expressed in cartilage of osteoarthritis patients, and its high expression can block chondrocytes in G0/G1 phase by targeting Akt gene, and induce apoptosis of chondrocytes.

The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel.

We previously reported that treatment with P-glycoprotein (P-gp) substrates promotes in vitro invasion in multidrug-resistant (MDR) breast cancer cells. This effect is initiated by the P-gp pump function and mediated by interaction of P-gp with some unknown component(s). However, the underlying mechanism(s) remains poorly understood. Here we confirm a novel physical interaction between P-gp and cellular prion protein (PrP(c)). Blocking P-gp activity or depletion of PrP(c) inhibited paclitaxel (P-gp substrate)- induced invasion. Paclitaxel further facilitated the formation of P-gp/PrP(c) clusters residing in caveolar domains and promoted the association of P-gp with caveolin-1. Both caveolin-1 and the integrity of caveolae were required for the drug-induced invasion. In addition, the P-gp/PrP(c) complex also played an important role in anti-apoptotic activity of MCF7/Adr cells.These data provide new insights into the mode by which MDR breast cancers evade cytotoxic attacks from P-gp substrates and also suggest a role for P-gp/ PrP(c) interaction in this process.

COX-2/PGE2 facilitates fracture healing by activating the Wnt/ß-catenin signaling pathway.

OBJECTIVE: The aim of this study was to explore the influence of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) on fracture healing by activating the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: In this study, 36 adult Sprague-Dawley (SD) rats raised in our laboratory were selected as research objects. The rats were subjected to fracture surgery on the middle part of the right femoral shaft. Subsequently, they were randomly divided into the control group and experimental groups (including experimental group A and experimental group B). Rats in experimental group A were injected with PGE 2 or COX-2 selective inhibitor NS-398, while rats in experimental group B were injected with PGE2 (5 µmol/L). Meanwhile, rats in the control group were injected with the same amount of normal saline. After that, the transcriptional levels of PEG2, COX-2, vascular endothelial growth factor (VEGF) and ß-catenin in rats of the experimental group A, experimental group B and control group were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) assay. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were conducted to determine the changes in protein levels of PEG2, COX-2, VEGF and ß-catenin in rats of the experimental group A, experimental group B and control group. The expression level of VEGF in bone tissues at fracture ends of rats in the experimental group A, experimental group B and control group was observed through the hematoxylin-eosin (HE) staining. Furthermore, micro-computed tomography (CT) was employed to evaluate callus formation. RESULTS: The transcriptional and translational levels of COX-2, ß-catenin and VEGF in rats of experimental group A treated with COX-2 inhibitors were significantly down-regulated when compared with those of the control group, showing statistically significant differences (p<0.05). However, the levels of these genes were markedly elevated in the experimental group B treated with PGE2 in comparison with those in the control group, and the differences were statistically significant (p<0.05). After 6 weeks, HE staining showed that the expression level of VEGF in rats of the experimental group B was remarkably higher than that of the experimental group A (p<0.05). Micro-CT results revealed that the mean trabecular plate density (MTPD) of rats in the experimental group B (73.29±5.4) was markedly higher than the number of osteoblasts (49.6±3.9) in the experimental group A, showing a statistically significant difference (p<0.05). CONCLUSIONS: COX-2/PGE2 facilitates fracture healing by activating the Wnt/ß-catenin signaling pathway.

miR-940 promotes spinal cord injury recovery by inhibiting TLR4/NF-κB pathway-mediated inflammation.

OBJECTIVE: The aim of this study was to investigate the effects of miR-940 and Toll-like receptor 4/Nuclear Factor κB (TLR4/NF-κB) pathways on inflammatory responses and spinal cord injury (SCI). MATERIALS AND METHODS: This study first established a model of spinal cord injury in mice. The grip force measurement was used to detect the recovery of the forelimb, left forelimb and right forelimb of SCI mice. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of miR-940 and macrophage receptor TLR4 in SCI mice. In addition, the protein levels of TLR4 and inducible nitric oxide synthase (iNOS) in SCI mice were detected by Western blot. MiR-940 mimic was injected into the injured area of SCI mice to explore the effect of miR-940 overexpression on TLR4 and myeloperoxidase (MPO) expression as well as the protein levels of TLR4, P65 and iNOS. Furthermore, the grip strength of SCI mice with double forelimb, left forelimb and right forelimb was detected by the grip force test after miR-940 overexpression. RESULTS: Compared with the sham-operated mice, the grip strength of the forelimb, left forelimb, and right forelimb of the SCI group showed significant obstacles. Meanwhile, the expression of miR-940 was remarkably decreased in SCI mice along with significant elevation of the inflammatory response-related factors including TRL4 and iNOS. Then we injected SCI mice with miR-940 mimics into the spinal cord injury area and found that miR-940 overexpression decreased the expression levels of TLR4 and MPO. At the same time, the overexpression of miR-940 markedly decreased the protein levels of TLR4, P65, and iNOS in SCI mice. In addition, miR-940 overexpression improved the grip strength of the left and right forepaws and the simultaneous grip strength of the two claws of the SCI mice than those of the simple injury group. CONCLUSIONS: High expression of miR-940 can promote the recovery of spinal cord injury by downregulating the TLR4/NF-κB signaling pathway and inhibiting inflammation.

MicroRNA-23c inhibits articular cartilage damage recovery by regulating MSCs differentiation to chondrocytes via reducing FGF2.

OBJECTIVE: The aim of the study was to explore the role of microRNA-23c in the differentiation of marrow stromal cells (MSCs) to chondrocytes and its potential mechanism. MATERIALS AND METHODS: MSCs were first isolated from rat bone marrow for cell culture. Surface antigens of MSCs (CD29 and CD34) were identified by flow cytometry. MSCs were induced for chondrogenic differentiation in MCDM (Mesenchymal Stem Cell Chondrogenic Differentiation Medium) for 0, 3, and 7 days, respectively, followed by detection of RUNX2, microRNA-23c and FGF2 expressions by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Alcian blue staining was performed to access proteoglycan deposition in MSCs transfected with microRNA-23c mimics or inhibitor. Western blot was conducted to detect the protein expressions of ACAN and COL2A1 in MSCs. The binding condition between microRNA-23c and FGF2 was verified by dual-luciferase reporter gene assay. Finally, MSCs were co-transfected with microRNA-23c mimics and FGF2 overexpression plasmid for rescue experiments. RESULTS: On the fourth day of MSCs isolation, MSCs were in an elongated shape. Flow cytometry results showed positive expression of CD29 and negative expression of CD34, which were consistent with MSCs phenotype. QRT-PCR data elucidated that the mRNA levels of RUNX2 and FGF2 gradually increased, whereas microRNA-23c expression decreased with the prolongation of chondrogenic differentiation. Transfection of microRNA-23c mimics in MSCs remarkably elevated microRNA-23c expression. Alcian blue staining showed that microRNA-23c overexpression results in less proteoglycan deposition in MSCs than that of controls. Both mRNA and protein expressions of ACAN and COL2A1 decreased after microRNA-23c overexpression. Dual-luciferase reporter gene assay confirmed that FGF2 binds to microRNA-23c. Further Western blot results demonstrated that FGF2 expression is negatively regulated by microRNA-23c. FGF2 overexpression reversed the inhibitory effects of microRNA-23c on proteoglycan deposition, as well as expressions of ACAN and COL2A1. CONCLUSIONS: MicroRNA-23c expression decreases during chondrogenic differentiation of MSCs, which inhibits MSCs differentiation to chondrocytes by inhibiting FGF2.

[Efficacy and safety of CTD and PCD regimens in treatment of patients with newly diagnosed multiple myeloma].

Objective: To observe the efficacy and safety of CTD (cyclophosphamide, thalidomide, dexamethasone) and PCD (bortezomib, cyclophosphamide, dexamethasone) regimens in treatment of patients with newly diagnosed multiple myeloma (NDMM) . Methods: A retrospective analysis was carried out on 88 cases of NDMM patients admitted to our hospital from July 2013 to January 2016, including 49 cases in CTD group and 39 cases in PCD group. The outcomes of two different regimens were analyzed, including response, prognosis, and adverse events. Results: The total overall remission rates (ORR, better than PR) of CTD and PCD were 65.3% (32/49) and 84.6% (33/39) , while very good partial response (VGPR) were 30.6% (15/49) and 53.8% (21/39) , and differences were statistically significant (P=0.041, P=0.028) . The median follow-up was 11.5 (3-33) months. The median progression-free survival (PFS) was (23.0±4.5) months in CTD groups, but it was not achieved in PCD group, with statistically significant differences (P=0.050) . Medial overall survival was not achieved in both two groups, without statistically significant difference (P=0.257) . There were statistical differences between patients with minor response (MR) and patients without MR in medium OS in CTD group (P=0.005) , and there were statistical difference between patients with VGPR and without VGPR in medium OS in CTD group (P=0.042) . Infection was a common adverse event in two groups. The incidences of peripheral neuropathy and herpes zoster were markedly higher in PCD group than CTD group, and the incidences of thrombus, palpation and rash, etc., were higher in CTD group. Conclusion: Both CTD and PCD regimens were effective first-line induction chemotherapy choice for NDMM. PCD regimen is better than CTD in treatment power and deep remission.

Metabolic changes in the urine of andrographolide sodium bisulfite-treated rats.

In recent years, andrographolide sodium bisulfite (ASB) has been reported to cause acute renal failure frequently in clinical practice. We hypothesized that changes in metabolic profile could have occurred after administration of ASB. To investigate the metabolic changes caused by ASB-induced nephrotoxicity, metabonomics method was utilized to depict the urine metabolic characteristics and find the specific urine biomarkers associated with ASB-induced nephrotoxicity. Sprague-Dawley rats were randomly assigned into three experimental groups. They received a single daily injection of vehicle (0.9% sodium chloride solution) or ASB at a dose of 100 or 600 mg kg(-1) day(-1) for 7 days. Twelve-hour urine was collected after the last administration. The routine urinalysis was measured by a urine automatic analyzer while urinary metabolites were evaluated using gas chromatography/mass spectrometry. The acquired data were processed by multivariate principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal PLS-DA. After 7-day administration of ASB, the positive urine samples in protein, occult blood, and ketones were increased, presenting dose dependence. The PCA and PLS-DA models were capable of distinguishing the difference between ASB-treated group and control. Biomarkers such as 1,5-anhydroglucitol, d-erythro-sphingosine, and 2-ketoadipate were identified as the most influential factors in ASB-induced nephrotoxicity.

An enhanced cAMP pathway is responsible for the colonic hyper-secretory response to 5-HT in acute stress rats.

5-hydroxytryptamine (5-HT) is involved in the stress-induced alteration of colonic functions, specifically motility and secretion, but its precise mechanisms of regulation remain unclear. In the present study, we have investigated the effects of 5-HT on rat colonic mucosal secretion after acute water immersion restraint stress, as well as the underlying mechanism of this phenomenon, using short circuit current recording (I(SC)), real-time polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbance assays. After 2 h of water immersion restraint stress, the baseline I(SC) and 5-HT-induced I(SC) responses of the colonic mucosa were significantly increased. Pretreatment with selective 5-HT(4) receptor antagonist, SB204070, inhibited the 5-HT-induced colonic I(SC) response by 96 % in normal rats and 91.2 % in acute-stress rats. However, pretreatment with the selective antagonist of 5-HT(3) receptor, MDL72222 or Y-25130, had no obvious effect on 5-HT-induced I(SC) responses under either set of conditions. Total protein expression of both the mucosal 5-HT(3) receptors and the 5-HT(4) receptors underwent no significant changes following acute stress. Both colonic basal cAMP levels and foskolin-induced I(SC) responses were significantly enhanced in acute stress rats. 5-HT significantly enhanced the intracellular cAMP level via 5-HT(4) receptors in the colonic mucosa from both control and stressed animals, and 5-HT-induced cAMP increase in stressed rats was not more than that in control rats. Taken together, the present results indicate that acute water immersion restraint stress enhances colonic secretory responses to 5-HT in rats, a process in which increased cellular cAMP accumulation is involved.

Propofol inhibits burn injury-induced hyperpermeability through an apoptotic signal pathway in microvascular endothelial cells.

Recent studies have revealed that an intrinsic apoptotic signaling cascade is involved in vascular hyperpermeability and endothelial barrier dysfunction. Propofol (2,6-diisopropylphenol) has also been reported to inhibit apoptotic signaling by regulating mitochondrial permeability transition pore (mPTP) opening and caspase-3 activation. Here, we investigated whether propofol could alleviate burn serum-induced endothelial hyperpermeability through the inhibition of the intrinsic apoptotic signaling cascade. Rat lung microvascular endothelial cells (RLMVECs) were pretreated with propofol at various concentrations, followed by stimulation with burn serum, obtained from burn-injury rats. Monolayer permeability was determined by transendothelial electrical resistance. Mitochondrial release of cytochrome C was measured by ELISA. Bax and Bcl-2 expression and mitochondrial release of second mitochondrial-derived activator of caspases (smac) were detected by Western blotting. Caspase-3 activity was assessed by fluorometric assay; mitochondrial membrane potential (Δψm) was determined with JC-1 (a potential-sensitive fluorescent dye). Intracellular ATP content was assayed using a commercial kit, and reactive oxygen species (ROS) were measured by dichlorodihydrofluorescein diacetate (DCFH-DA). Burn serum significantly increased monolayer permeability (P<0.05), and this effect could be inhibited by propofol (P<0.05). Compared with a sham treatment group, intrinsic apoptotic signaling activation - indicated by Bax overexpression, Bcl-2 downregulation, Δψm reduction, decreased intracellular ATP level, increased cytosolic cytochrome C and smac, and caspase-3 activation - was observed in the vehicle group. Propofol not only attenuated these alterations (P<0.05 for all), but also significantly decreased burn-induced ROS production (P<0.05). Propofol attenuated burn-induced RLMVEC monolayer hyperpermeability by regulating the intrinsic apoptotic signaling pathway.

Growth promoting effect of zinc supplementation in infants of high-risk pregnancies.

This study was made to determine whether zinc deficiency is one of the factors involved in growth retardation of infants of high-risk pregnancies. The high risk factors were hypertension of pregnancy, diabetes mellitus, congenital heart disease, chronic nephritis, rheumatic heart disease and hyperthyroidism. 102 neonatal infants were divided into 3 groups: breast fed group, 37 cases; test group, 32 cases formula-fed with supplementary zinc 1.14-2.28 mg/kg/d; and control group, 33 cases formula-fed and supplemented with Vitamin B complex as placebo. The groups were divided by double-blind and randomized method. There were no differences in the 3 groups in sex ratio, growth status and serum zinc concentration at the beginning of the study. Anthropometric data were obtained at 0, 3 and 6 months.

Umbilical cord blood lead levels in Shanghai, China.

This study was designed to determine the cord blood lead (BPb) levels of babies born in one urban area of Shanghai, and to preliminarily identify the demographic, social environment and prenatal factors which have an effect on the cord BPb concentrations. From August to November 1993, umbilical cord blood samples were obtained from 605 live newborns in the Yangpu Maternal and Child Hospital. 257 samples were excluded from measurement because of clotting. In 348 cord samples, the geometric mean of cord BPb levels was 9.2 micrograms/dl, with a 95% confidence interval of the mean 8.86-9.54 (micrograms/dl). 142 babies (40.8%) had cord BPb levels of 10 micrograms/dl or greater. As a result of this high percentage of newborns with BPb levels equal to or greater than 10 micrograms/dl, we estimate that each year in the Shanghai City about 60,000 newborns are at risk for developing neuropsychological deficiencies caused by maternal lead exposure during pregnancy. To investigate the factors affecting cord blood levels, the subjects with levels greater than the 70th percentile (10.7 micrograms/dl) (n = 104) and less than the 30th percentile (7.4 micrograms/dl) (n = 104) were selected to compare the demographic, environment and prenatal medical history. Increased BPb levels at birth were associated with maternal passive smoking, a family member being occupationally exposed to lead, proximity to major traffic way, household coal combustion, neighborhood coal combustion, low level of maternal occupations, and the increasing occurrence of having the high lead foodstuff pidan (preserved duck egg) during pregnancy. We conclude that prenatal lead exposure has become an important health issue for young children in Shanghai.

The adverse effect of marginally higher lead level on intelligence development of children: a Shanghai study.

We surveyed 128 preschool children in a lead-polluted area in Shanghai to study the relationship between blood lead level and neuropsychological functions, assessed by age-appropriate psychological tests. The geometric means of blood lead level was 21.7 + -10.8 micrograms/dl. Of 47 children aged below 30 months, there was no significant difference in BSID indices between the high and low lead subjects, although the high lead children tended to have poorer development scores than the low lead ones. On the other hand, of 81 children older than 46 months, the WPPSI IQ scores showed highly significant negative correlation with blood lead level. Step-wise regression and multiple analysis of covariance techniques were employed to find out and control the confounding factors. Even when 21 non-lead variables were considered, the IQ difference between high and low lead groups remained statistically significant. We concluded that the children, especially those older than 46 months, in the area investigated, did suffer from lead toxicity causing impairment in intelligence development. We support the view that marginally higher lead level in children should be taken seriously.

[Purification and identification of red ginseng polypeptides].

Two new polypeptides named RGPI and RGPII were isolated from the Chinese drug red ginseng for the first time. They were identified as propadecopeptide and pentadecopeptidex on the basis of analysis of amino acid composition and determination of molecular weight. Further-more, the effects of RGPs on the content of polysaccharides and the activity of succinodehydrogenase in the 2BS cells of the lung of human embryo were studied.

[Isolation and structure elucidation of cirensenosides O and P from the leaves of Oplopanax elatus Nakai].

Two new triterpenoid saponins were isolated from the leaves of Oplopanax elatus Nakai. By measuring physical and chemical constants and spectral data, their structures were elucidated as 3-epi-oleanolic acid 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D- glucopyranosyl (1-->6)-beta-D-glucopyranoside; 3-O-beta-D-glucopyranosyl betulinic acid 28-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside and named as cirensenosides O and P, respectively.

[Effects of Paeonia-glycyrrhiza decoction on changes induced by cisplatin in rats].

In order to study the effects of Paeonia-Glycyrrhiza decoction (PGD) on the changes induced by cisplatin in rats, platinum-wire bipolar electrodes were inserted into the serosal membrane of the small intestine and migrating myoelectric complex (MMC) was used as index. After intravenous injection of cisplatin at doses of 4 mg/kg, the duration of the MMC cycles was significantly shorter than that of normal MMC cycles (P < 0.05) while the duration of phase III was remarkably prolonged comparing with that of normal phase III (P < 0.01) with latent period of 53.2 +/- 20.4 minutes. Taking PGD orally, cisplatin no longer induced the changes of MMC. The results suggest that PGD has marked adjusting effects on the changes of MMC induced by cisplatin. This might be one of the causes of PGD in relieving diarrhea induced by cisplatin in rats.

[Optimum number of mixed peripheral blood samples by membrane filtration technique for mass blood survey of filariasis].

The membrane filtration technique has been used widely in the evaluation of effect of control and survey of filariasis. The present study was made to explore an optimum number of mixed peripheral blood samples and a mathematical model of work load for this method in surveying filariasis. By analysing the correlation between the microfilaremia rate and the optimum number of mixed peripheral blood samples and applying the theory of Binomial Distribution or Poisson Distribution, the authors reckoned a table for estimating the number of filariasis cases in villages with different microfilarial rates and different population as well as the optimum number of mixed peripheral blood samples.

[Studies on the chemical constituents of the roots of Aralia continentalis Kitag].

Seven compounds were isolated from the roots of Aralia continentalis. Four of these compounds were identified as ent-kaur-16-en-19-oic acid, beta-sitosterol glucoside (daucosterol), beta-sitosterol and 16 alpha-hydroxy-(-)-kauran-19-oic acid. It is the first time that 16 alpha-hydroxy-(-)-karan-19-oic acid and beta-sitosterol glucoside were isolated from this plant.

[Effect of Curcuma zedoaria (Berg.) Bosc on the myoelectric activity of uterus in rats and study of its mechanisms].

OBJECTIVE: To investigate the effect of Curcuma zedoaria on the myoelectric activity of uterus in virgin rats and study its mech anisms. METHOD: A pair of bipolar Ag-AgCl electrodes were implanted on the serosal surface of uterus in rats to observe the effect of C. zedoaria on the myoelectric activity of uterus before and after the five agonists were injected intraperitoneally. RESULT: Decoction of C. zedoaria significantly increases the spike area, the duration and the number of bursts of action potentials of the uterine smooth muscle and its effect is related dosage. Atropine and phentolamine decreased the exciting effect of C. zedoaria, whereas verapamil, diphenhydramine and indomethacin have no effect on the excitation of C. zedoaria. CONCLUSION: C. zedoaria has obvious exciting effect on the smooth muscle of uterus in rats, and its mechanisms may be associated with M-receptor and alpha-receptor.

Emodin induces chloride secretion in rat distal colon through activation of mast cells and enteric neurons.

BACKGROUND AND PURPOSE: Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active component of many herb-based laxatives. However, its mechanism of action is unclear. The aim of the present study was to investigate the role of mast cells and enteric neurons in emodin-induced ion secretion in the rat colon. EXPERIMENTAL APPROACH: Short-circuit current (I(SC)) recording was used to measure epithelial ion transport. A scanning ion-selective electrode technique was used to directly measure Cl(-) flux (J(Cl)-) across the epithelium. RIA was used to measure emodin-induced histamine release. KEY RESULTS: Basolateral addition of emodin induced a concentration-dependent increase in I(SC) in colonic mucosa/submucosa preparations, EC(50) 75 µM. The effect of emodin was blocked by apically applied glibenclamide, a Cl(-) channel blocker, and by basolateral application of bumetanide, an inhibitor of the Na(+) -K(+) -2Cl(-) cotransporter. Emodin-evoked J(Cl)- in mucosa/submucosa preparations was measured by scanning ion-selective electrode technique, which correlated to the increase in I(SC) and was significantly suppressed by glibenclamide and bumetanide. Pretreatment with tetrodotoxin and the muscarinic receptor antagonist atropine had no effect on emodin-induced ΔI(SC) in mucosa-only preparations, but significantly reduced emodin-induced ΔI(SC) and J(Cl)- in mucosa/submucosa preparations. The COX inhibitor indomethacin, the mast cell stabilizer ketotifen and H(1) receptor antagonist pyrilamine significantly reduced emodin-induced ΔI(SC) in mucosa and mucosa/submucosa preparations. The H(2) receptor antagonist cimetidine inhibited emodin-induced ΔI(SC) and J(Cl)- only in the mucosa/submucosa preparations. Furthermore, emodin increased histamine release from the colonic mucosa/submucosa tissues. CONCLUSIONS AND IMPLICATIONS: The results suggest that emodin-induced colonic Cl(-) secretion involves mast cell degranulation and activation of cholinergic and non-cholinergic submucosal neurons.