To elucidate the molecular mechanism of sunitinib-mediated suppression of HCC, a panel of well-characterized signaling molecules was utilized in sunitinib-treated HCC cells. As shown in Fig. 5A, sunitinib had no effect on total STAT3 LDK378 supplier and pSTAT3(S727) in Sk Hep1 cells; however, this treatment dramatically inhibited pSTAT3(T705). A similar dose-dependent, but incomplete reduction in pSTAT3(T705) was observed in Hep G2 cells (Fig. 5A). In contrast, no inhibitory effects were observed on STAT5, pERK-1/2, and p38 MAPK in either cell line. Only modest inhibitory effects were detected on pSTAT5 and pAkt with more notable

effects in Sk Hep1 cells (Fig. 5A). To further confirm whether STAT3 is involved in the sunitinib-mediated suppression of HCC, we utilized wtSTAT3 and a dominant negative variant of STAT3. This dnSTAT3 inhibited the proliferation of Sk Hep1 and Hep G2 (Fig. 5B), induced the apoptosis (Fig. 5C), and dramatically decreased colony formation (Fig. 5D). In contrast, overexpression of wtSTAT3 rescued the sunitinib-mediated suppression of proliferation (Fig. 5E) and apoptosis Enzalutamide price (Fig. 5F). These results indicate that STAT3 is involved in sunitinib-mediated

inhibition of HCC cell growth. To investigate the effect of sunitinib on blocking tumor growth in vivo, tumor-bearing mice were orally administered sunitinib. Monthly MRI was used to monitor change in tumor size. The results in Fig. 6A demonstrate progressive tumor growth from 130 mm3 to 180 mm3 in vehicle-treated tumor-bearing mice, whereas sunitinib-treated mice demonstrate a continual decrease in tumor burden from 130 mm3 to 100 mm3 3 months posttreatment. Western blot revealed decreased levels of pSTAT3 (T705) in the tumors from sunitinib-treated mice compared to vehicle-treated mice. Survivin, a direct downstream target of STAT3, is also reduced in the sunitinib-treated tumors (Fig. 6B). However, no detectable differences were found in the levels of ERK, pERK, Akt, pAkt, and total STAT3. In a second in

vivo analysis, dnSTAT3-transfected Tag tumorigenic hepatocytes do not produce tumors in C57BL/6 mice, whereas the empty vector-transfected hepatocytes demonstrate progressive tumor growth (Fig. 6C). These results indicate that sunitinib treatment induces the partial regression of established this website orthotopic HCC and is associated with a reduction in pSTAT3 within the tumor. Suppression of STAT3 is crucial in both innate and adaptive immune responses against tumors.8, 21 Therefore, we considered that sunitinib treatment may activate the tumor-specific immune response. Sunitinib treatment of tumor-bearing mice dramatically enhanced the accumulation of adoptively transferred TCR-I T cells following immunization (Fig. 7A,B). This level of accumulation was consistently higher than that observed in normal C57BL/6 mice (17% versus 6.9%).

On the other hand, the exacerbated inflammatory response could just be secondary to increased hepatic lipid accumulation in ethanol-fed

lipin-1LKO mice. Up-regulation of hepatic proinflammatory cytokines and excess production of reactive oxygen species (ROS) in lipin-1LKO mice are likely to contribute to markedly elevated serum makers of liver injury. Additional studies evaluating the ability of lipin-1 to repress the activity of transcriptional factors such as NFATc4 or NF-κB and to attenuate the production of cytokines or ROS in response to LPS or ethanol in Kupffer cells are currently under investigation in our laboratory. The Lieber-DeCarli liquid diets enriched in polyunsaturated fat promotes ethanol-induced liver injury in rodents.[1] Our present study used a modified Lieber-DeCarli low-fat ethanol-containing liquid diet.[17] It MAPK inhibitor is possible that hepatic lipin-1 may be influenced by dietary fat and composition. We are currently investigating the effects of dietary fat and composition on ethanol-mediated impairments of lipin-1. The present study demonstrates that ethanol metabolism by

way of ADH and ALDH2 induces nucleocytoplasmic shuttling of lipin-1α, inhibiting PGC-1α activity and causing fat accumulation in cultured hepatocytes. These in vitro findings further support the notion that depletion of hepatic nuclear lipin-1 in lipin-1LKO mice may largely contribute to the drastic liver responsiveness to ethanol challenge. The role of hepatic ethanol metabolism-induced production of metabolites, redox see more state shift, or ROS in regulation

of lipin-1α nucleocytoplasmic shuttling merits investigation. In summary, using liver-specific lipin-1-null mice fed an ethanol-containing diet, we demonstrated for the first time that liver-specific deletion of lipin-1 leads to the rapid onset and progression of alcoholic steatohepatitis, providing novel insights into the biological click here function of lipin-1 in alcoholic steatohepatitis. Our present findings suggest that the development of nutritional or pharmacological agents to enhance nuclear lipin-1 activity could be a promising approach toward developing new options for the prevention and treatment of human alcoholic steatohepatitis. Additional Supporting Information may be found in the online version of this article. “
“Crohn’s disease (CD) is a multifactorial disorder with a pivotal role of the genetic component. A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in CD. The purpose of this study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD in the Chinese population. One hundred patients with CD and 190 healthy individuals were genotyped for the HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis. The genotype frequency of the PstI polymorphism did not differ between patients and controls.

29 SREBP-1c knockout mice are protected against a high-fat diet–induced and alcohol-induced steatosis,36 favoring the view that de novo lipogenesis is a key mechanism for fat accumulation in the liver.37, 38 It appears that ER stress can override cholesterol inhibition of SREBP processing. It is thought that down-regulation of protein synthesis in response

to ER stress decreases Insig, which in turn results in the cleavage and release of SREBPs and their subsequent activation.39 SREBP activation may also be indirect; insulin resistance induced by ER stress TGF-beta inhibitor induces SREBP expression.40, 41 A key point in this field is the significance of TG accumulation. Mounting evidence supports the view that the formation of TGs may detoxify fatty acids.42-44 In this scenario, TG accumulation is a sign of increased lipogenesis, which means that increased exposure to lipotoxic fatty acids may accompany steatosis.

Thus, the key to the pathogenetic HM781-36B cost importance of ER stress in NAFLD is the bidirectional interplay of ER stress and lipogenesis that promotes insulin resistance as well as lipotoxicity. GRP78 overexpression has been shown to inhibit insulin-induced SREBP-1c activation in cultured primary hepatocytes.32 There is some evidence that the master regulator GRP78 (BIP) may play a role in retaining the SREBP-SCAP complex in the ER, but this is not fully defined. GRP78 overexpression has been shown to inhibit ER stress response and SREBP activation in ob/ob

mice.32 Induction of ER stress response by treatment with tunicamycin leads to alteration of SREBP expression and hepatic steatosis in HepG2 cells,45 with some studies reporting activation and some down-regulation of SREBP-1c depending on the severity and duration of ER stress response.45, 46 Clearly, the effects of tunicamycin are extreme and probably do not reflect the effects of UPR/ER stress response on lipid metabolism in naturally occurring liver diseases.47 IRE1α has been implicated in liver steatosis via its downstream product XBP1. Independent selleck products of SREBPs, XBP1 regulates genes involved in fatty acid and TG synthesis such as stearoyl-CoA desaturase 1 (Scd-1) and acetyl CoA carboxylase-2 (Acc2). Selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia. These mice did not demonstrate hepatic steatosis when placed on a high-carbohydrate diet.48 XBP+/− mice fed a high-fat diet for 3 weeks developed hyperinsulinemia, type 2 diabetes, and insulin resistance. An increase in PERK phosphorylation was demonstrated, as was an increase in JNK activity.49 ER stress has been shown to cause insulin resistance. ER stress promotes JNK-dependent serine phosphorylation of IRS-1, which in turn inhibits insulin receptor signaling and leads to insulin resistance.49 Inhibition of the eIF2α arm of the UPR by dephosphorylation of eIF2α via GADD34 leads to improved steatosis and glucose tolerance in mice.

29 SREBP-1c knockout mice are protected against a high-fat diet–induced and alcohol-induced steatosis,36 favoring the view that de novo lipogenesis is a key mechanism for fat accumulation in the liver.37, 38 It appears that ER stress can override cholesterol inhibition of SREBP processing. It is thought that down-regulation of protein synthesis in response

to ER stress decreases Insig, which in turn results in the cleavage and release of SREBPs and their subsequent activation.39 SREBP activation may also be indirect; insulin resistance induced by ER stress www.selleckchem.com/products/PD-0332991.html induces SREBP expression.40, 41 A key point in this field is the significance of TG accumulation. Mounting evidence supports the view that the formation of TGs may detoxify fatty acids.42-44 In this scenario, TG accumulation is a sign of increased lipogenesis, which means that increased exposure to lipotoxic fatty acids may accompany steatosis.

Thus, the key to the pathogenetic learn more importance of ER stress in NAFLD is the bidirectional interplay of ER stress and lipogenesis that promotes insulin resistance as well as lipotoxicity. GRP78 overexpression has been shown to inhibit insulin-induced SREBP-1c activation in cultured primary hepatocytes.32 There is some evidence that the master regulator GRP78 (BIP) may play a role in retaining the SREBP-SCAP complex in the ER, but this is not fully defined. GRP78 overexpression has been shown to inhibit ER stress response and SREBP activation in ob/ob

mice.32 Induction of ER stress response by treatment with tunicamycin leads to alteration of SREBP expression and hepatic steatosis in HepG2 cells,45 with some studies reporting activation and some down-regulation of SREBP-1c depending on the severity and duration of ER stress response.45, 46 Clearly, the effects of tunicamycin are extreme and probably do not reflect the effects of UPR/ER stress response on lipid metabolism in naturally occurring liver diseases.47 IRE1α has been implicated in liver steatosis via its downstream product XBP1. Independent selleck screening library of SREBPs, XBP1 regulates genes involved in fatty acid and TG synthesis such as stearoyl-CoA desaturase 1 (Scd-1) and acetyl CoA carboxylase-2 (Acc2). Selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia. These mice did not demonstrate hepatic steatosis when placed on a high-carbohydrate diet.48 XBP+/− mice fed a high-fat diet for 3 weeks developed hyperinsulinemia, type 2 diabetes, and insulin resistance. An increase in PERK phosphorylation was demonstrated, as was an increase in JNK activity.49 ER stress has been shown to cause insulin resistance. ER stress promotes JNK-dependent serine phosphorylation of IRS-1, which in turn inhibits insulin receptor signaling and leads to insulin resistance.49 Inhibition of the eIF2α arm of the UPR by dephosphorylation of eIF2α via GADD34 leads to improved steatosis and glucose tolerance in mice.

This will need to be verified empirically and future studies examining the role of longer acting products in PWH who are physically active are needed.

Overweight and obesity are associated with a more rapid decline in joint health in young males with haemophilia. A 10-year longitudinal find more study involving more than 6000 males with severe haemophilia under the age of 21 years, demonstrated a significant increase in limitation of lower limb joint range of motion in those who were overweight and obese compared to those with a normal BMI [63]. Maintaining body weight within the normal range therefore appears important to minimize the risk of joint deterioration. With the exception of prophylaxis, there are currently no evidence-based sports injury prevention strategies for children with haemophilia. While haemarthroses can occur in the absence of acute joint derangements, prevention of sports injury is paramount. Advice to children with haemophilia is, therefore, based on Ribociclib molecular weight guidelines in healthy children and there are relatively few evidence-based injury prevention strategies in children

and adolescents. To date, research on sports injury prevention in young healthy populations has focussed largely on the use of protective equipment and training programmes [64]. There has been little emphasis on rule changes and behavioural change in sport injury prevention research. The other limitation in injury prevention research is that most interventions have been directed at a particular sporting population or preventing a particular injury, for example, anterior cruciate ligament prevention programmes. This makes it difficult to devise widespread evidence-based injury prevention strategies. Proprioceptive and neuromuscular

training programmes have been shown to reduce lower limb injuries in sport [65]. Randomized control trials involving balance training alone or in combination with strength and plyometric training, selleck chemicals llc have shown a significant decrease in reported lower limb injuries in adolescents and young adults, with training programmes that range from once weekly to seven times weekly and which run for a duration of 3–12 months [66-70]. While these training programmes reduce injury during the timeframe of the research study, injury rates often return to pretrial levels following conclusion of the studies highlighting the difficulty of putting effective training strategies in to practice [71]. Protective equipment has an important role for PWH competing in certain sports. There are two broad categories of protective equipment that reduce risk of injury. One type is for joint stabilization, for example, ankle taping or bracing, while the other type is designed to disperse contact forces, for example, shin pads and bicycle helmets.

6 Thus, liver injury through the TNF-α pathway requires hepatocyte sensitization accomplished by pretreatment with D-galactosamine (GalN) that depletes uridine triphosphate and inhibits de novo RNA synthesis.7 NF-κB regulates expression of antiapoptotic genes such as IAPs, c-FLIP, TRAFs, and Bcl family members, among others.8 The Wnt/β-catenin pathway is an important player in liver biology with roles in development, Wnt antagonist regeneration, and tumorigenesis (reviewed in Nejak-Bowen and Monga9). However, little is known about its role in hepatocyte survival, although evidence exists that β-catenin ablation renders hepatocytes susceptible to apoptosis in development,

regeneration, and more recently in hepatic ischemia-reperfusion injury.10 We used β-catenin conditional knockout

(KO) mice and their wild-type (WT) littermates to test susceptibility to Fas and TNF-α. Whereas Fas activation had comparable effects in WT and KO mice, a paradoxical survival advantage was observed in KO mice after GalN/LPS treatment. We demonstrate that the p65/β-catenin complex in hepatocytes underwent dynamic changes to regulate NF-κB activation, and a decrease in β-catenin protein levels, both in vivo and in vitro, led to robust and protracted p65 nuclear translocation and activation. Conversely, β-catenin stabilization suppressed NF-κB activity. Thus, we provide evidence that β-catenin–NF-κB interactions may be altered in hepatic pathologies and Gemcitabine that modulation of the complex may be uniquely exploited therapeutically for certain forms of liver injury. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CBP, β-catenin–CREB binding protein; cDNA, complementary DNA; EGFR, epidermal growth factor receptor; GalN, D-galactosamine; GS, glutamine synthetase; GSK-3β, glycogen synthase kinase-3β; H&E, hematoxylin and eosin; HCC, hepatocellular carcinoma; HGF, check details hepatocyte growth factor; IκB, inhibitor of κB; IHC, immunohistochemistry; KO, knockout; LiCl, lithium chloride; LPS, lipopolysaccharide; phospho-p65, Ser-536-phosphorylated

p65; siRNA, small interfering RNA; TLR-4, Toll-like receptor 4; TNF-α, tumor necrosis factor-α; TUNEL, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling; WB, western blotting; WT, wild-type. Conditional β-catenin knockout mice (C57BL/6) were generated as described.11 Ctnnb1loxp/loxp; Alb-Cre+/− mice are referred to as KO mice and Ctnnb1loxp/loxp; Alb-Cre−/− or Ctnnb1loxp/Wt; Alb-Cre−/− mice are referred to as WT mice. All studies were approved by the University of Pittsburgh’s Institutional Animal Care and Use Committee and were conducted in accordance with National Institutes of Health guidelines. For complete methods, see the Supporting Information.

“
“(Headache 2011;51:726-733) Objective.— An imbalance between activity of inhibitory and facilitatory intracortical circuits could play a central role in migraine etiology. We used input–output curves to achieve further information about intracortical

excitability of motor cortex in migraine with aura. Methods.— Input–output curves were measured in the right abductor pollicis brevis muscle at rest in 12 patients suffering from migraine with aura and 8 healthy subjects. Stimuli were delivered at intensity MK 2206 ranging from 100% to 160% of resting motor threshold with 10-second inter-stimulus intervals. Seven patients were studied before and during treatment with levetiracetam. Results.— Results showed a greater motor-evoked potential amplitude in response to increasing intensity of stimuli in patients compared to controls (P < .02). This increased facilitatory effect was abolished by levetiracetam (P < .005). Conclusions.— Our findings

support the hypothesis of an interictal Nivolumab cortical hyper-responsivity in migraine patients that appears to be normalized by levetiracetam. This effect could support the potential therapeutic role of levetiracetam in migraine with aura prevention. “
“Lacrimal neuralgia has only recently been described in 3 cases. None of them had an underlying lesion or any precipitating event, so they were considered primary. Here, we report a symptomatic case due to surgical trauma. A 73-year-old woman started having a circumscribed pain at age 66 after left cataract surgery. The pain was located in a small area of her left temple next to the lateral canthus. Pain attacks lasted 1-2 minutes, and were associated with allodynia. The attacks were precipitated by light touch on the eyelid or the temple, and were also evoked by palpation of the superoexternal angle of the orbit. An anesthetic blockade performed at the emergence of the lacrimal nerve resulted in complete and long-lasting pain relief. Lacrimal neuralgia may be due to local trauma. This new case not only reinforces the existence of a specific neuralgia of the lacrimal nerve, but also introduces

a classification into primary and secondary forms based on the etiology. “
“Migraine and neck find more pain can be critical causes of disability. The contribution of neck pain for the overall disability of individuals with migraine remains unknown. To contrast the disability experienced by individuals with episodic and chronic migraine with and without neck pain as captured by the Neck Disability Index. Disability due to neck pain was assessed using the Neck Disability Index in individuals with episodic or chronic migraine seen at a university-based headache center. Neck disability was defined as mild (score ranging from 5 to 14 points), moderate (15-24 points), severe (25-34 points) or complete (35 points or higher). To compare differences between groups, a chi-square test was applied.

This information has been fed into a database which now has >30 years cumulated clinical experience with which we can evaluate epidemiological factors such changes in disease status, morbidity and mortality. It is interesting that this database precedes the HIV/AIDS epidemic and therefore provides an opportunity to assess its impact on the epidemiological characteristics of the haemophiliac population. RAD001 clinical trial The survey was not compulsory and so the number of responses each year varied, and on average approximately two-thirds of clinics replied in any given year. In 2009/2010 the database included information from almost 10 000 patients with bleeding disorders: ∼600

with haemophilia B, ∼4000 with haemophilia A and ∼5000 with von Willebrand disease. The factor activity and inhibitor

responder rates for patients with haemophilia A and B in the periods 2009/2010 and 2008/2009 are shown in Table 4. One question we sought to answer using the database was whether anti-PD-1 antibody inhibitor the prevalence of inhibitors was increasing following the introduction of a number of recombinant products. Interestingly, between the years 2000 and 2010 we observed a marked decrease in the proportion of patients with inhibitors, and this may be explained in part by the better immune tolerability of newer recombinant products. With regard to von Willebrand disease there were almost 5000 patients on the database in 2009/2010, but less than 20% (861 of 4995) of these had ristocetin cofactor activity levels ≤30% [38]. The HIV/AIDS epidemic had a catastrophic impact on the haemophiliac population, but we appear to have overcome the worst of it, and in the 2009/2010 cohort 372 (4.1%) haemophiliac patients were HIV positive and there were only six deaths which were AIDS related. This compares with thousands of haemophiliac patients who were

HIV positive in the 1990s. The improvement in the clinical picture in relation to HIV/AIDS is reflected by a significantly reduced death rate resulting from HIV over the last 15 years (Fig. 3). When we compare results for the periods selleckchem 1982–1995 to 1996–2010 there was an approximate 15-fold reduction in deaths related to HIV in the haemophiliac population. Over the period 1978–2010 the incidence of liver disease has varied widely. However, the trend has been for liver disease to increase in the German haemophilic population and this is particularly noticeable when the pre-1996 period is compared with the post 1996 period. Overall, there was almost a twofold increase in liver disease post 1996 (P < 0.002). Up to 1998 the number of deaths due to cancer per year was very low with only isolated cases reported. However, since 1998 the rate of reporting of malignancy-related deaths has increased sharply (Fig. 4). This is due to an increase in the number of hepatocellular carcinomas which, in turn, is related to the increased number of patients that are hepatitis C positive.

Conclusions:  These results suggest that on first HCC recurrence, a curative treatment should be considered in order to prevent a second recurrence if possible. In addition, IFN therapy contributes

to improved prognosis after curative treatment, even in patients with recurrent HCC. “
“Primary biliary cirrhosis (PBC) is characterized by unknown etiologies, anti-mitochondrial antibodies, injury of the biliary duct and the lack of a definite remedy. The etiologies of PBC have been well-discussed, including microorganisms and xenobiotics as the triggers for initiating the disease, and an abnormality of immune-tolerance. Recently, several animal models of PBC have been developed that may lead to the development of new therapies. Here, we reviewed the articles that address

the etiology of PBC and the therapy for this disease for the confirmation of our current BMS-354825 supplier positions and future directions. “
“Genome-wide studies in inflammatory bowel disease (IBD) have allowed us to understand Crohn’s disease and ulcerative colitis as forms of related autoinflammatory disorders that arise from a multitude of pathogenic Selleckchem FDA-approved Drug Library origins. Proteomics and metabolomics are the offspring of genomics that possess unprecedented possibilities to characterize unknown pathogenic pathways. It has been about a decade since proteomics was first applied to IBD, and 5 years for metabolomics. These techniques have yielded novel and potentially important findings, but turning these results into beneficial patient outcomes remains challenging. This review recounts the history and context of clinical IBD developments before and after proteomics and metabolomics IBD in this field, discusses the challenges in consolidating high complexity data with physiological

understanding, and provides an outlook on the emerging principles that will help interface the bioanalytical laboratory with IBD prognosis. In selleck kinase inhibitor 1990, the human genome project was launched by the National Human Genome Research Institute (Maryland, USA) and the US Department of Energy with the mammoth objective of sequencing the entire human genetic code.[1, 2] The international consortium charged with the task endeavored to make universally available genetic sequences as soon as they were discovered, and these were rapidly mined by scientists in search of a genetic basis for the inflammatory bowel diseases (IBD).[1, 3-8] Results were immediate, with the first Crohn’s disease (CD) gene (IBD1 locus on chromosome 16) being reported by Hugot and colleagues in 1996, quickly followed by successive discoveries of other CD and ulcerative colitis (UC) susceptibility loci.[6, 9, 10] The human genome contains within it the initial conditions by which disease manifests in the body.

The aim of this research was to conduct a systematic review on the association between dental erosion (DE) and gastroesophageal reflux disease (GERD) and the effect of saliva’s flow rate, buffering capacity and oral microbial changes caused by GERD. Methods: All descriptive, analytical studies up to December 2011 that have relevant objectives,

proper sampling method and sufficient results were included by searching PubMed and Scopus electronic data bases. Results: Fifteen studies were selected according to our inclusion criteria (10 in adult and 5 in children population). There was a strong association between DE and GERD in the adult population, and the relationship in the children population GSK-3 inhibition was found to be of less importance. Conclusion: Early diagnosis and treatment of refluxed acid in both age groups through lifestyle changes and medications an prevent further damage and tooth loss Key Word(s): 1. Dental Erosion; 2. GERD; 3. saliva; 4. systemic review; Presenting

Author: PEIQIN WANG Additional Authors: CHENGDANG WANG Corresponding Metformin chemical structure Author: PEIQIN WANG, CHENGDANG WANG Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University Objective: Diarrhea-predominant irritable bowel syndrome (IBS-D) is characterized by elevated colonic luminal serine proteases activity, which may be come from gut bacteria. The aims of this study were (1) to analysis the relationship of fecal serine proteases activity with IBS symptoms, small intestinal bacterial overgrowth (SIBO), serum interleukin-6 (IL-6) and erythrocyte sedimentation rate (ESR), (2) to study the effects of antibiotics

and probiotics on fecal serine proteases activity and IBS symptoms improvement. Methods: Fecal serine proteases activity, lactulose hydrogen breath test (LHBTs), IL-6, and ESR were detected in 65 cases of patients with IBS-D. Antibiotics learn more and probiotics (metronidazole 0.4 tid+ levofloxacin 0.2 bid+ Bifico 0.42 bid) were administrated to 14 patients with LHBT-positive IBS-D for one week, and the alteration of fecal serine proteases activity and symptoms improvement were investigated. Results: (1) A positive correlation was detected between fecal serine proteases activity and the degree of abdominal pain discomfort (r = 0.37, P = 0.007). (2) The activity of fecal serine proteases was no significant difference between LHBT-positive (5.23∼130.62 (median 24.81) U/mg protein) and negative (26.06∼177.77 (median 52.80) U/mg protein) IBS-D patients (P = 0.18).