Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis

BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in gallbladder contractility.AIM To investigate the origin of slow wave(SW)in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.METHODS Methylene blue(MB)with light was used to establish selective impaired ICCs gallbladder tissue.Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control(NC),AC12h,AC24h,and AC48h groups of guinea pigs.Hematoxylin and eosin and Massonstained gallbladder tissues were scored for inflammatory changes.ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy.The alterations of c-Kit,α-SMA,cholecystokinin A receptor(CCKAR),and connexin 43(CX43)were assessed using Western blot.RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility.The frequency of SW and gallbladder contractility were significantly lower in the AC12h group.Compared with the NC group,the density and ultrastructure of ICCs were remarkably impaired in the AC groups,especially in the AC12h group.The protein expression levels of c-Kit were significantly decreased in the AC12h group,while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility.The density and ultrastructure of ICCs were clearly impaired in the early stage of AC,while CCKAR and CX43 were significantly reduced at end stage.

Modeling cell contractility responses to acoustic tweezing cytometry

Acoustic tweezing cytometry(ATC)is a recently developed method for cell mechanics regulation.Tar-geted microbubbles,which are attached to integrins and subsequently the actin cytoskeleton,anchor,amplify and transmit the mechanical energy in an acoustic field inside the cells,eliciting prominent cy-toskeleton contractile force increases in various cell types.We propose that a mechanochemical con-version mechanism is critical for the high efficiency of ATC to activate cell contractility responses.Our models predict key experimental observations.Moreover,we study the influences of ATC parameters(ul-trasound center frequency,pulse repetition frequency,duty cycle,and acoustic pressure),cell areas,the number of ATC stimuli,and extracellular matrix rigidity on cell contractility responses to ATC.The simu-lation results suggest that it is large molecules,rather than small ions,that facilitate global responses to the local ATC stimulation,and the incorporation of visible stress fiber bundles improves the accuracy of modeling.

Mechanisms underlying the impaired contractility of diabetic cardiomyopathy

Cardiac dysfunction is a well-known consequence of diabetes,with sustained hyperglycaemia leading to the development of a cardiomyopathy that is independent of cardiovascular disease or hypertension.Animal models of diabetes are commonly used to study the pathophysiology of diabetic cardiomyopathy,with the hope that increased knowledge will lead ultimately to better therapeutic strategies being developed.At physiological temperature,left ventricular trabeculae isolated from the streptozotocin rat model of type 1 diabetes showed decreased stress and prolonged relaxation,but with no evidence that decreased contractility was a result of altered myocardial Ca2+handling.Although sarcoplasmic reticulum(SR)Ca2+reuptake appeared slower in diabetic trabeculae,it was offset by an increase in actionpotential duration,thereby maintaining SR Ca2+content and favouring increased contraction force.Frequency analysis of t-tubule distribution by confocal imaging of ventricular tissue labeled with wheat germ agglutinin or ryanodine receptor antibodies showed a reduced T-power for diabetic tissue,but the differences were minor in comparison to other models of heart failure.The contractile dysfunction appeared to be the result of disrupted F-actin in conjunction with the increased typeⅠcollagen,with decreased myofilament Ca2+sensitivity contributing to the slowed relaxation.

EFFECTS OF DESENSITIZATION AND REBOUND TO ADENOSINE ON ACTION POTENTIAL AND CONTRACTILITY IN ATRIAL CELLS IN GUINEA-PIGS

Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.

Contractility detection of isolated mouse papillary muscle using myotronic Myostation-Intact device

Background:To understand the relationship between myocardial contractility and ex-ternal stimuli,detecting ex vivo myocardial contractility is necessary.Methods:We elaborated a method for contractility detection of isolated C57 mouse papillary muscle using Myostation-Intact system under different frequencies,volt-ages,and calcium concentrations.Results:The results indicated that the basal contractility of the papillary muscle was 0.27±0.03 mN at 10 V,500-ms pulse duration,and 1 Hz.From 0.1 to 1.0 Hz,con-tractility decreased with an increase in frequency(0.45±0.11-0.10±0.02 mN).The voltage-initiated muscle contractility varied from 3 to 6 V,and the contractility gradu-ally increased as the voltage increased from 6 to 10 V(0.14±0.02-0.28±0.03 mN).Moreover,the muscle contractility increased when the calcium concentration was increased from 1.5 to 3 mM(0.45±0.17-1.11±0.05 mN);however,the contractility stopped increasing even when the concentration was increased to 7.5 mM(1.02±0.23 mN).Conclusions:Our method guaranteed the survivability of papillary muscle ex vivo and provided instructions for Myostation-Intact users for isolated muscle contractility investigations.

Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.

Inhibition of rat prostate smooth muscle contractility by extracts of Costus speciosus(crepe ginger)

Background:This study examined the chemistry and biological effects of Costus speciosus(J.Koenig)Sm.(C.speciosus)which has been traditionally used by Sarawak natives to treat urological disorders for centuries.Methods:This study assesses the efficacy of C.speciosus in treating urological disorders by investigating its effects on the contractility of isolated prostate glands since this is the most effective way to relieve lower urinary tract symptoms that accompany benign prostatic hyperplasia.Plants were collected and extracts of C.speciosus rhizome,root,leaf and stem were made using water at different temperatures.Results:C.speciosus rhizome and root decoction(boiling,about 100℃)combination extract(2 mg/mL)inhibited electrical field stimulation-induced neurogenic contractions of isolated rat prostatic gland by 44±8%(p=0.01,n=4);whereas room temperature(about 20℃)rhizome and root combination extract inhibited electrical field stimulation contractions by 62±8%(p=0.003,n=4).C.speciosus rhizome(p=0.0004,n=6),root(p<0.0001,n=6)and stem(p=0.0057,n=6)room temperature extracts inhibited electrical field stimulation-induced contractions of rat prostatic smooth muscle but leaf extract did not(p=0.09,n=6).Contractions mediated by exogenous administration of noradrenaline,acetylcholine,adenosine 5’-triphosphate or tyramine were only weakly inhibited by rhizome extract.Fractions of C.speciosus rhizome room temperature extract separated by preparative high-performance liquid chromatography and evaluated by isolated organ bath bioassay revealed that inhibitory activity of the extract was due to highly polar soluble components present in the extract.Conclusion:C.speciosus extracts exert a direct inhibitory effect on prostate tissue which is likely to be therapeutically beneficial in treating lower urinary tract symptoms associated with benign prostatic hyperplasia.

Influence of Contractility on Myocardial Ultrasonic Integrated Backscatter and Cyclic Variation in Integrated Backscatter

To evaluate the effects of left ventricular contractility on the changes of aver age image intensity (AII) of the myocardial integrated backscatter (IB) and cyclic variation in IB (CVIB), 7 adult mongrel dogs were studied. The magnitude of AII and CVIB were measured from myocardial IB carves before and after dobuta mine or propranolol infusion. Dobutamine or propranolol did not affect the magnitude of AII (13.8±0.7 vs 14.7±0.5, P >0.05 or 14.3±0.5 vs 14.2±0.4, P >0.05). However, dobutamine produced a significant increase in the magnitude of CVIB (6.8±0.3 vs 9.5±0.6, P <0.001) and propranolol induced significant decrease in the magnitude of CVIB (7.1±0.2 vs 5.2±0.3, P <0.001). The changes of the magnitude of AII and CVIB in the myocardium have been demonstrated to reflect different myocardial physiological and pathological changes respectively. The alteration of contractility did not affect the magnitude of AII but induced significant change in CVIB. The increase of left ventricular contractility res ulted in a significant rise of the magnitude of CVIB and the decrease of left ventricular contractility resulted in a significant fall of the magnitude of CVIB.

Differential Effects of K⁺Channel Blockers on Phasic Contractility of Transverse and Longitudinal Rat Detrusor Strips

Spontaneous phasic contractions of detrusor smooth muscle are pivotal to the normal bladder filling process. The role of K+ channels in mediating phasic contractions has been investigated on different occasions, but only in detrusor strips isolated longitudinally. In this study, the effects of individual K+ blockers were examined in both transverse and longitudinal detrusor strips. Detrusor strips were isolated transversely and longitudinally from young adult rat bladders. Tension before and after the introduction of K+channel blockers was measured using a myograph. Phasic activity was determined by calculating the integral of tension fluctuations. Phasic activity of transverse strips was increased under tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP) and iberiotoxin (IbTx) treatments. Longitudinal phasic activity was increased under charybdotoxin (ChTx) treatment. Neither glibenclamide (Glib) nor apamin treatment elicited any significant effect in both transverse and longitudinal phasic activity. The results indicated that phasic activity was mediated differently depending on the contractile direction. Data from this study reiterate that in addition to the conventional longitudinal direction, the transverse direction also presents significance when examining the contractility of a sac-like organ like the bladder.

Effects of hydrogen sulfide on electrophysiological features and contractility of guinea pig ventricular papillary muscle

Objective: To investigate the effects of hydrogen sulfide (H2S) on electrophysiological features and contractility of left ventricular papillary muscle in guinea pigs. Methods: 48 healthy guinea pigs were randomly divided into 6 groups: Normal control group, NaHS50 μmol/L group, NaHS100 μmol/L group and NaHS 200 μmol/L group, with 8 rats in each group. Preparation of Guinea Pig Left Ventricular Papillary Muscle Specimens was made and the effects of H2S on electrophysiological features of guinea pigs left ventricular papillary muscle were observed by standard microelectrode intracellular recording technique. The indexes included resting potential (RP), over-shoot (OS), amplitude of action potential (APA), maximum rate of depolarization (Vmax), 20%, 50% and 90% repolarization time (APD20, APD50 and APD90) and average rate of repolarization;The effects of H2S on the contractility of left ventricular papillary muscle were observed by using isolated cardiac tissue perfusion system and tension transducer. The indexes included the contraction amplitude of papillary muscle (%), the maximum rate of active tension rising (+dT/dtmax, mg/s) and the maximum rate of active tension decreasing (-dT/dtmax, mg/s). Results: Compared with the normal control group, the absolute value of RP was increased, APD50 and APD90 were shortened, the average repolarization speed was accelerated (P<0.05), and the contractility of papillary muscle was decreased by 50, 100 and 200 μmol/L NaHS. When KATP channel blocker Glibenclamide (Gli;20 μmol/L) or L-type calcium channel opener BayK8644 (0.5 μmol/L) were administered simultaneously with H2S, the physiological effects of H2S on papillary muscle cells were blocked separately. Conclusion: H2S can affect the electrophysiological features and contractility of left ventricular papillary muscle, and this effect is achieved by affecting KATP channel and L-type calcium channel.

Assessment of Contractility for Fontan Connections

This study is performed to investigate the effect of Fontan operations on cardiac contractility. Investigation of articles about the contractility in Fontan published in PubMed up to now revealed that the measurement of contractility values did not include the rudimentary ventricle. Connections between right atrium and right ventricle as well as right atrium and pulmonary artery were studied in the same group as well. In our opinion, for the single ventricular physiology, the RA-RV and RA-PA connected patients’ preload and afterload values cannot be calculated in the same group since volume of rudimentary ventricles must be considered from this point of view as well.

The Initial Tangent of the Femoral Arterial Pressure Increase Is an Estimate of Left Ventricular Contractility in Patients Undergoing Cardiacsurgery

Purpose: Assessment of contractile function is a major challenge in patients with left ventricular dysfunction, especially during cardiac surgery. The initial tangent of the femoral arterial pressure increase (tanin) has recently been described to be an estimate of left ventricular (LV) contractility. To confirm these findings tanin was compared to various indices of LV performance in patients undergoing cardiac surgery. Methods: Data from 17 patients were evaluated retrospectively. Myocardial performance was estimated by the echocardiographic indices ejection fraction (EF), shortening fraction (FS), circumferential fiber shortening velocity (Vcf), the parameters of pulse contour analysis area under the curve (AUC) and tanin. Measurements were taken before and after cardiopulmonary bypass (CPB). Results: Tanin increased significantly (813 ± 216 mmHg/s vs. 1490 ± 450 mmHg/s, p < 0.05) after CPB, as well as Vcf (0.89 ± 0.14 circ/s vs. 1.47 ± 0.27 circ/s, p < 0.05) and EF (65% ± 7% vs. 74% ± 6%, p < 0.05). FS did not change (40.7% ± 7% vs. 46.5% ± 5%, p = 0.30). AUC significantly dropped after CPB (435 ± 54 mmHg*s vs. 263 ± 27 mmHg*s). Tanin and Vcf correlated strongly (r = 0.70, p < 0.001), while tanin showed only weak correlation with EF (r = 0.36, p = 0.037). There was no significant correlation with FS (r = 0.31, p = 0.079). Tanin and AUC correlated inversely (r = -0.62, p < 0.001). Conclusions: While showing little or no correlation with EF and FS respectively, tanin correlated well with the less preload-dependent parameter Vcf, thus suggesting that tanin may be used as an easily accessible estimate of LV contractility during cardiac surgery.

Significance of preoperative detrusor contractility to the postoperative assessment of prostatectomy for benign prostatic hyperplasia

Objective To study the value of preoperative detrusor contractility to the outcome assessment of prostatectomy for benign prostatic hyperplasia ( BPH) . Methods A total of 109 patients with BPH were analyzed. Their ages ranged from 62 to 83 years with a mean of

Effects of docosahexaenoic acid or arachidonic acid supplementation on the behavior of cardiomyocytes derived from human pluripotent stem cells

Background:Human heart changes its energetic substrates from lactate and glucose to fatty acids during the neonatal period.Noticing the lack of fatty acids in media for the culture of cardiomyocytes derived from human pluripotent stem cells(hiPS-CM),researchers have supplemented mixtures of fatty acids to hiPS-CM and reported the enhancement in the maturation of hiPS-CM.In our previous studies,we separately supplemented two polyunsaturated fatty acids(PUFAs),docosahexaenoic acid(DHA)or arachidonic acid(AA),to rat fetal cardiomyocytes and found that the supplementations upregulated the expressions of mRNAs for cardiomyocyte differentiation,fatty acid metabolism,and cellular adhesion.The enhancement in cellular contractility was attributed to the improvement in intercellular connection rather than a direct enhancement of the contractile force.Methods:This study reports the successive results of the effects of DHA or AA supplementation on hiPS-CM.In addition to the contractile force and mRNA measurements used in the previous study,we further investigated the effect of different cellular aggregations on the contractile force output by means of finite element analysis,measured glucose and fatty acids metabolites,and assessed cTNT and MLC2v expressions through immunofluorecsence evaluation.Results:It showed that the sole supplementation of albumin-conjugated DHA or AA can be taken up by hiPS-CM without other uptake-enhancing factors,and the supplementations may activate the CD36_ERRγmetabolic pathway.DHA or AA supplementation increased the cellular contractile ratio on collagen gels and AA supplementation stimulated hiPS-CM aggregation to form cellular clusters.The enhancement effect on the hiPS-CM contractile force was modest since the increase in contractile force was not significant.AA supplementation was more effective than DHA supplementation because it significantly upregulated mRNA expressions of P300 and CD36.However,finite element analysis showed that the formation of clusters on a collagen gel attenuated the contractile force exerted by the gel on its surroundings.Conclusion:DHA and AA,as having been supplemented in infant formulas,have no direct and significant enhancement effect on the performance of the hiPS-CM when they were supplemented individually,although they were able to enter the cellular metabolic system.The AA supplementation showed some auxiliary effect on the maturation of hiPS-CM,which is worthy of further investigation under the consideration of membrane composition alteration and remodeling of membrane molecules.

Study on the Treatment of Benign Prostate Hyperplasia Combined with Underactive Bladder Detrusor Contraction by Transurethral Plasma Enucleation of the Prostate

Objective: Exploring the clinical efficacy of transurethral plasma enucleation of the prostate in the treatment of benign prostatic hyperplasia with underactive bladder detrusor contractility. Methods: Retrospective analysis of the clinical data of 68 patients with benign prostatic hyperplasia and underactive detrusor muscle contractility treated by our department from July 2021 to July 2022. The above patients all met the diagnosis of benign prostatic hyperplasia, excluding prostate cancer and urethral stricture. Urodynamics showed a decrease in the contractile force of the bladder detrusor muscle, and the surgical equipment used Olympus bipolar plasma resection equipment method. Divide the above patients into two groups: the experimental group of 34 patients who underwent transurethral plasma enucleation of the prostate and the control group of 34 patients who underwent transurethral plasma resection of the prostate. Evaluate the preoperative clinical baseline level and postoperative observation indicators of the two groups of patients, and compare the statistical differences between the two groups. Results: Both groups of patients successfully completed the surgery, and there were no serious complications such as rectal or bladder perforation during the surgery, with less bleeding. The postoperative QOL, IPSS, Qmax, and residual urine volume of patients undergoing transurethral plasma enucleation and resection of the prostate were significantly improved compared to those before surgery (P 0.05). Conclusion: Transurethral enucleation of the prostate has good efficacy and safety in the treatment of benign prostatic hyperplasia combined with weakened detrusor muscle contractility. Compared with traditional electric resection surgery, the efficacy is more significant. In terms of the main complications of the surgery, although there are slightly more patients with temporary urinary incontinence after prostate enucleation, there is no statistically significant difference compared to after electric resection, and they can recover to normal in the short term.

Phytochemical Analysis and Contractile Effects of Aqueous and Hydroethanolic Extracts of Anastatica hierochuntica L. (Brassicaceae) on the Isolated Uterus of Mice

Background: Anastatica hierochuntica L. (Brassicaceae) has been claimed to treat various conditions, including complicated childbirth. The principal objective of this research was to provide scientific evidence on the contractile effect of the aqueous and hydroethanolic extracts of the whole plant from A. hierochuntica during labor. Method: Qualitative and quantitative methods helped identify and quantify the phytoconstituents in both extracts. The antioxidant activity was studied using four standard methods (ABTS, DPPH, FRAP, and LPO). Results: The inhibitory power of the extracts on pro-inflammatory enzymes such as 15-lipoxygenase and phospholipase A2 was determined. The contractile effects of the extracts were evaluated using isolated pregnant mice uteri. Steroids, triterpenoids, flavonoids, tannins, coumarins, and reduced compounds were identified in both extracts. The hydroethanolic extract exhibited higher content of hydrolyzable tannins (15.07 ± 0.24 mg tannic acid equivalent/g) than the aqueous decoction (11.8 ± 0.69 mg TAE/g). The extracts demonstrated the ability to scavenge DPPH and ABTS radicals, reduce ferric ions, and inhibit especially lipid peroxidation. No significant difference was noted in the phospholipase inhibition between the extracts and betamethasone. The hydroethanolic extract displayed the most significant anti-lipoxygenase activity with an IC50 value of 55.82 ± 1.15 μg/mL. The lethal dose (LD50) of extracts was estimated to be superior to 2000 mg/kg body weight (bw). The ability of the samples to produce one cm amplitude of contraction at 50% effective concentrations (EC50) was 5.33 × 10−8 ± 0.32 mg/mL for oxytocin, 1.51 ± 0.08 mg/mL for aqueous extract and 3.57 ± 0.61 mg/mL for hydroethanolic extract. Conclusion: These findings could provide evidence for using Anastatica hierochuntica to facilitate childbirth.

Double-crosslinked PNIPAM-based hydrogel dressings with adjustable adhesion and contractility

Rapid post-wound closure is necessary to avoid wound infection and promote scar-free healing when skin trauma occurs.In this study,new types of hydrogel dressings with adjustable contractility were fabricated based on N-isopropyl acrylamide/sodium alginate/graphene oxide(P/SA/GO).Then,the chitosan(CS)solution was used as a bridging polymer to achieve tissue adhesion to the hydrogel.The results show that the hydrogel based on poly(N-isopropyl acrylamide)(PNIPAM)not only has the ability to self-shrink but also can adjust the rate of shrinkage through near-infrared thermal stimulation.At the same time,high adhesion strength(7.86±1.22 kPa)between the tissue and the dressing is achieved through the introduction of bridging polymers(CS),and the coating area of the bridging polymer can be adjusted to achieve regional adhesion.The mouse total skin defects experiments have shown that sutures-free wound closure in the early stages of wound healing could be obtained by adjusting the material temperature.Besides,the dressings can promote scar-free wound healing by reducing inflammatory cell infiltration and collagen deposition.These results indicate that double-crosslinked PNIPAM-based hydrogel dressings with adjustable adhesion and contractility proposed in this study provide a candidate material for achieving trackless wound healing.

Th17 Cells Influence Intestinal Muscle Contraction during Trichinella spiralis Infection

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility. The aim of the study was to use this experimental model to elucidate if Thl 7 cells are involved in the development of gastrointestinal hypermotility. Colonic smooth muscle contractility was investigated in response to acetylcholine. The levels of IL-17, IL-23 and TGF-β1 in colon were measured by Western blotting. Flow cytometric detection of intracellular IFN-7/IL-4/ IL- 17 cytokine production was used to analyze the proportions of CD4＋ T cells subsets in colon. Our results showed that colonic muscle contractility was increased 2 weeks post infection （PI） and stayed high 12 weeks PI when no discernible inflammation was present in the gut. The proportion of Th17 cells and the expression of IL-17 were up-regulated in colon 2 weeks PI and returned to normal 8 weeks PI. The content of IL-17 was correlated with the colonic smooth muscle hypercontracility 2 weeks PI. Meanwhile, TGF-β1 was increased 2 weeks PI, while IL-23 was normal. Our results suggest that Th17 cells affect the colonic muscle contractility in mice infected with Trichinella spiralis at intestine stage but not at muscle stage and the effect of Th17 cells on muscle contractility might be induced by TGF-β1. Other cytokines might be involved in the hypercontracility of colonic smooth muscle at muscle stage.

Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart

The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR function.Since β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases.