The IL-4-induced Vorinostat Epigenetics inhibitor downregulation of melanogenesis was inhibited by treating NHMs with a JAK2 inhibitor AG490 or STAT6 siRNA. In conclusion, the involvement of the IL-4-induced JAK2-STAT6 signaling and the IFN gamma- or IL-17A-dependent antimelanogenic IL-6 production should be considered as one of the mechanisms explaining the association with hypopigmention in skin diseases. Journal of Investigative Dermatology (2013) 133, 528-536; doi:10.1038/iid.2012.331;

published online 20 September 2012″
“Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this

article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on “The Chemical Ecology of Disease Vectors” at the 25th Annual ISCE meeting in Neuchatel, Switzerland. Alisertib in vitro The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.”
“Sulfanilamide reacted with acryloyl chloride to give 4-(N-acrylamido)benzenesulfonamide (ABA), which converted to the corresponding polymer (PABA) upon treatment with initiator at 75A degrees C. Various copolymers https://www.selleckchem.com/products/qnz-evp4593.html formed from ABA with acrylamide (AA), acrylonitrile

(AN), and N-(thiazol-2-yl)acrylamide (TA) at different ratios (50 : 50, 70 : 30 and 30 : 70) were prepared. The polymer and copolymers were characterized using IR, H-1 NMR, C-13 NMR and mass spectroscopy, thermogravimetry, and scanning electron microscopy. The drug release from polymeric chain and copolymers was studied at 37A degrees C and pH 8.4. The drug release was highly increased upon adding sodium chloride at various concentrations, 0.1%, 0.5% and 0.9%. The drug release from the polymer and copolymer chains was measured using a UV-visible spectroscopy technique. Antimicrobial activity of the polymer and copolymers was studied. It is established that the ABA copolymer with TA is more effective as compared to other copolymers.”
“The potential energy surfaces of the initial reactions of ethylene insertion for the Ziegler-Natta catalysis with bridging groups of Cp ligands were studied by ab initio MO and density functional methods. Three metals (Ti, Zr, and Hf) in the Zeigler-Natta catalysis and eight bridging groups (BH, CH2, NH, O, AlH, SiH2, PH, and S) were treated. For the complex formation between ethylene and metallocenes, two type structures (vertical and horizon) were found.

“
“Is complexity growth the result of a continuous process or a sudden breakthrough? An increased energy density rate is the effect or the cause of a complexity leap? Should we approach complexity change by the perspective of components

behaviour or system’s space geometry? In this work we address some of the questions regarding the theoretical approach to complexity selleck screening library change. For this purpose a case study drawn by the productive structure and the transport system is considered. We would like here to propose an example in which the system structure is reshaped in a more energy intensive fashion as to increase the components’ interactions due to a symmetry rupture in the space. Flows throughout the system are thereby incremented in a discontinuous way by a complexity leap. In the case study, we analyze how the productive system evolved its structure, between 1970s and 1990s, to increase interactions among its parts and thus further develop the transport sub-system. A two-stage shift has been considered:

the fordian and the post-fordian productive structure. The second structure, given the same amount of parts, has been shown to increase the degree of freedom (path PF-03084014 length and path diversity) of the system. The underlying evolutionary pattern is then analyzed. This evolutionary pattern relies on the hypothesis that thermodynamic evolutionary systems are characterized by an ever growing influx of energy driven into the system by self-catalytic processes that must find their way through the constraints of the system. The system initially disposes of the energy by expanding, in extent and in the number of components, up to saturation due to inner or outer constraints. The two counteractive forces, constraints and growing energy flux, expose the system to new gradients. Every new (spatial) gradient upon the system

represents a symmetry rupture in the components’ space. By exploring a new gradient, the system imposes further restrictions on its components and increases its overall degree of freedom. The counteractive effects of reduction/increase of degree selleck kinase inhibitor of freedom concern two different hierarchical levels and occur at two different space and time scales. (C) 2009 Elsevier B.V. All rights reserved.”
“Aims: Cisplatin (CDDP) is a platinum-based drug that is widely used in cancer chemotherapy, but the development of resistance in tumor cells is a major weakness of these treatments. Several mechanisms have been proposed to explain cisplatin resistance, and disruption of certain cellular pathways could modulate drug sensitivity to cisplatin. A lower level of cross-resistance to cisplatin leads to better outcomes in clinical use. Main methods: Cross-resistance was assessed using cisplatin resistant lung cancer cell line A549/CDDP.

Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland-Altman plots.\n\nResults Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower

fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (+/- 2SD) of -15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, +/- 1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between -2 and +3 mm.\n\nConclusions see more This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring.”
“Genetic variants predicted

to seriously disrupt the function of human protein-coding genes so-called loss-of-function (LOF) variants-have traditionally been viewed in the context of severe Mendelian disease. However, recent large-scale sequencing and genotyping projects have revealed a surprisingly large number of Nepicastat chemical structure these variants in the genomes of apparently healthy individuals at least 100 per genome, including more than 30 in a homozygous state suggesting a previously unappreciated level of variation in functional gene content between selleck products humans. These variants are mostly found at low frequency, suggesting that they are enriched for mildly

deleterious polymorphisms suppressed by negative natural selection, and thus represent an attractive set of candidate variants for complex disease susceptibility. However, they are also enriched for sequencing and annotation artefacts, so overall present serious challenges for clinical sequencing projects seeking to identify severe disease genes amidst the ‘noise’ of technical error and benign genetic polymorphism. Systematic, high-quality catalogues of LOF variants present in the genomes of healthy individuals, built from the output of large-scale sequencing studies such as the 1000 Genomes Project, will help to distinguish between benign and disease-causing LOF variants, and will provide valuable resources for clinical genomics.”
“Methadone, an opioid analgesic, is used clinically in pain therapy as well as for substitution therapy in opioid addiction. It has a large interindividual variability in response and a narrow therapeutic index.

The

primary outcome measure was the change in systolic and diastolic BP between intervention and control groups.\n\nRESULTS\n\nIn total, 10 randomized controlled trials comprising 297 individuals were included in the analysis. The populations studied were either healthy normotensive adults or patients with prehypertension/stage I hypertension, Treatment duration ranged from 2 to 18 weeks. The mean BP change in the active treatment arms across all trials was -4.5 mm Hg (95% confidence interval selleck screening library (CI), -5.9 to -3.2, P < 0,001) for systolic BP and -2.5 mm Hg (95% CI, -3.9 to -1.2, P < 0.001) for diastolic BP.\n\nCONCLUSIONS\n\nThe meta-analysis confirms the BP-lowering capacity of flavanol-rich cocoa products in a larger set of trials than previously reported. However, significant statistical heterogeneity across studies could be found, and questions such as the most appropriate dose and the long-term side effect profile warrant further investigation before cocoa products can be recommended as a treatment option in hypertension.”
“The study was designed to evaluate the long-term efficacy and safety of the 28-day prolonged-release Autogel formulation of the somatostatin

analogue lanreotide (Lan-Autogel) in unselected patients with acromegaly. The study comprised four phases: washout; a double-blind comparison with placebo, at a single randomized dose selleck compound (60, 90 or 120 mg) of Lan-Autogel; a single-blind, fixed-dose

phase for four injections (placebo group was re-allocated to active treatment); and eight injections with doses tailored according to biochemical response. Serum samples were assessed for growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels, at weeks 4, 13, 14, 15, 16, 32 and 52. 108 patients were enrolled and 99 completed 52 Panobinostat mw weeks’ treatment. Four weeks after the first injection, serum GH levels decreased by > 50% from baseline in 63% of patients receiving Lan-Autogel compared with 0% receiving placebo (P < 0.001). After four injections, 72% of patients had a > 50% reduction in GH levels; 49% patients achieved GH levels a parts per thousand currency sign 2.5 ng/ml; 54% had normalized IGF-1; and 38% achieved the combined criterion of GH level a parts per thousand currency sign 2.5 ng/ml and normalized IGF-1. The corresponding proportions by week 52 were 82, 54, 59 and 43%, respectively. In patients not requiring dose escalation to 120 mg, 85% achieved biochemical control (combined criterion). Treatment was well tolerated by all patients. In conclusion, Lan-Autogel was effective in controlling GH and IGF-1 hypersecretion in patients with acromegaly and showed a rapid onset of action.”
“The antioxidant, antiradical, and membranotropic properties of newly synthesized compounds of the group of N-[3-hydroxy-3-(p-substituted phenyl)-1-propyl] amino acids were studied on model systems in vitro.

In addition, this E. coli isolate expressed the extended-spectrum beta-lactamase CTX-M-15, together with two 16S rRNA methylases, namely, ArmA and RmtB, conferring a high level of resistance

to aminoglycosides.”
“Successful precut sphincterotomy (PS) in difficult biliary cannulation (DBC) requires a large incision for deroofing the papilla. However, the high complication rate poses a substantial problem, in addition to the need for expert skills. Pancreatic stent placement could facilitate this procedure. Needle-knife precut papillotomy with a small incision using a layer-by-layer method over a pancreatic stent (NKPP-SIPS) could potentially improve the success rate and reduce the complication rate of PS.\n\nTo validate selleck compound the efficacy, feasibility and safety of NKPP-SIPS in DBC.\n\nTherapeutic MLN8237 mouse endoscopic retrograde cholangiopancreatography with a na < ve papilla was performed in 1619 cases between May 2004 and July 2011. We prospectively divided the patients chronologically, in terms of the period during which the procedure was performed,

into two groups: group A; needle-knife precut papillotomy (NKPP) performed between April 2004 and October 2006; group B; NKPP-SIPS performed between November 2006 and July 2011. The success rates and complication rates were evaluated. NKPP was performed without pancreatic stent placement and the cut was made starting at the papillary orifice, extended upward over a length of more than 5-10 mm for deroofing the I-BET-762 manufacturer papilla. On the other hand, in NKPP-SIPS, a pancreatic stent was placed initially as a guide, and to prevent post-ERCP pancreatitis, the incision was begun at the papillary orifice in a layer-by-layer fashion and extended upward in 1-2 mm increments, not going beyond the oral protrusion, finally measuring less than 5 mm in length.\n\nPS was performed in 8.3 % of the patients (134/1619). The cannulation success rate of PS in the entire group was 94.0 % (126/134). NKPP and NKPP-SIPS were performed in 36 and 98 of the patients, respectively. There was one case of major bleeding in group A, and no severe

complications in group B. The success rates of bile duct cannulation increased from 86.1 % (31/36) in group A to 96.9 % (95/98) in group B (p = 0.0189). The overall complication rate of PS was YC 33 % (12/36) in group A (major bleeding 8.3 %; mild to moderate pancreatitis 19.4 %; perforation requiring surgery 2.8 %), and 7.1 % (7/98) in group B (mild to moderate pancreatitis 6.1 %; minor perforation 1 %) (p < 0.001).\n\nNKPP-SIPS has significantly improved the success rate and reduced the complication rate of DBC, proving that a small incision starting at the orifice of the PS is sufficient, feasible and safe in DBC, when a pancreatic stent is inserted at the outset.”
“The quality of cold-stored livers declines with the extension of ischemic time and the risk of primary dys- or nonfunction increases.

As predicted, the NPT see more in fusiform gyrus is close to the stimulus duration and the NPT in dorsal anterior cingulate gyrus depends on the presence of an emotional distracter. Interestingly, the NPT in right but not left dorsal lateral prefrontal cortex depends on the stimulus emotional content. The summary measures of HRF obtained by a standard approach did not detect the variations observed in the NPT. Hum Brain Mapp, 2012. (C) 2010 Wiley Periodicals, Inc.”
“Murine cytomegalovirus (MCMV) brain infection stimulates microglial cell-driven proinflammatory chemokine production

which precedes the presence of brain-infiltrating systemic immune cells. Here, we show that in response to MCMV brain infection, antigen-specific CD8(+) T cells migrated into the brain and persisted as long-lived memory cells. The

role of these persistent T cells in the brain is unclear because most of our understanding of antimicrobial T cell responses comes from analyses of lymphoid tissue. Strikingly, memory T cells isolated from the brain exhibited an effector phenotype and produced IFN-gamma upon restimulation with viral peptide. Furthermore, we observed time-dependent and long-term activation of resident microglia, indicated by chronic MHC class II up-regulation and TNF-alpha production. The immune response in this immunologically restricted site persisted in the absence of active viral replication. Lymphocyte infiltrates were detected until 30 days post-infection (p.i.),

with CD8(+) and CD4(+) selleck products T cells present at a 3:1 ratio, respectively. We then investigated the role of IFN-gamma in chronic microglial activation by using IFN-gamma-knockout (GKO) mice. At 30 days p.i., GKO mice demonstrated a similar phenotypic brain infiltrate when compared to wild-type mice (Wt), however, MHC class II expression on microglia isolated from these GKO mice was significantly lower compared to Wt animals. When IFN-gamma producing CD8(+) T cells were reconstituted in GKO mice, MHC Navitoclax chemical structure class II up-regulation on microglial cells was restored. Taken together, these results suggest that MCMV brain infection results in long-term persistence of antigen-specific CD8(+) T cells which produce IFN-gamma and drive chronic microglial cell activation. This response was found to be dependent on IFN-gamma production by viral Ag-specific T cells during the chronic phase of disease.”
“Sickle cell trait (HbAS) associates with impaired urinary concentration, hematuria, and renal papillary necrosis, but its prevalence among African Americans with ESRD is unknown. We performed a cross-sectional study reviewing available hemoglobin phenotypes for 188 of 206 adult African-American patients receiving renal replacement therapy in four dialysis units.

It describes methodological approaches and main cultivation methods and discusses different problems arising during the application of these methods. One of the major problems is the negative effect of large-scale monoculture of seaweeds on natural benthic biocenoses. We express our views

on how to tackle the most acute problems of macroalgal farming on the basis of our own data and data from other authors. The sustainable use of natural monodominant seaweed communities is shown to A-1155463 in vivo be preferable to mariculture. A detailed analysis is given of various mariculture models and the latest achievements in the integrated farming of seaweeds, fish, crustaceans, and mollusks.”
“Protein phosphorylation is a key mechanism to regulate protein functions. However, the contribution of this protein modification to species divergence is still largely unknown. Here, we studied the evolution of mammalian phosphoregulation

by comparing the human and mouse phosphoproteomes. We found that 84% of the positions that are phosphorylated in one species or the other are conserved at the residue level. Twenty percent of these conserved sites are phosphorylated in both species. This proportion is 2.5 times more than expected by chance alone, suggesting that purifying selection is preserving phosphoregulation. However, we show that the majority of the sites that are conserved at the residue level are differentially phosphorylated between DMH1 datasheet species. These sites likely result from false-negative identifications due to incomplete experimental coverage, false-positive identifications and non-functional sites. In addition, our results suggest that at least 5% of them are likely to be true differentially phosphorylated sites and may thus contribute to the divergence in phosphorylation networks between mouse and humans and this, despite residue conservation between orthologous

proteins. We also showed that evolutionary turnover of phosphosites at adjacent positions ( in a distance range of HSP990 up to 40 amino acids) in human or mouse leads to an over estimation of the divergence in phosphoregulation between these two species. These sites tend to be phosphorylated by the same kinases, supporting the hypothesis that they are functionally redundant. Our results support the hypothesis that the evolutionary turnover of phosphorylation sites contributes to the divergence in phosphorylation profiles while preserving phosphoregulation. Overall, our study provides advanced analyses of mammalian phosphoproteomes and a framework for the study of their contribution to phenotypic evolution.”
“BackgroundThe WBC (the ratio between DIFF and BASO counts of the Sysmex XT-2000iV), hereafter defined as TNC (total nucleated cells), is high in effusions due to feline infectious peritonitis (FIP), as cells are entrapped in fibrin clots formed in the BASO reagent.

05). The expression of TLR4 at each time point in the control group was relatively low. Rats in https://www.selleckchem.com/products/netarsudil-ar-13324.html the modeling

group had the high expression of TLR4 in kidney’s glomerular basement membrane, proximal convoluted tubule and renal interstitial area since 2 w, with the significant difference compared to the control group (P<0.05). The expression in rats of the modeling group was higher than the one of the control group since the 2nd week. As the time flied, its expression increased, with the statistically significant difference between two groups (P<0.05). There was certain correlation between the protein expression of TLR4 and the increased serum titer of 24-hour urine protein excretion, serum creatinine, CRP and TNF-alpha. Conclusions: TLR4 may activate the immuno-inflammatory reactions to play a

role in the occurrence and development of the diabetic nephropathy.”
“Objective To assess the determinants of patients’ (PTGL) and physicians’ (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them.\n\nMethods. A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual SB273005 manufacturer analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within >= 2 cm), higher patient rating group (PTGL exceeding MDGL by > 2 cm), and lower patient rating group (PTGL less than MDGL by > 2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance.\n\nResults. The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed LY2090314 clinical trial by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher,

and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels.\n\nConclusion. Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the “disease experience” of patients, particularly pain and fatigue, is warranted for effective care of RA.”
“Cabergoline, an ergot-derived dopamine receptor agonist, is used widely in the treatment of Parkinson’s disease (PD) and hyperprolactinemia, but may cause heart valve fibrosis, retraction, and clinically significant regurgitation in PD patients.

Results: H. pylori was eradicated in 21 (46.6%) pts in the LAC group, while it was eradicated in 29 (64.4%) pts in the LACE

group. There was no statistical difference between the two groups (p=0.13). Conclusion: The eradication rate of H. pylori in children while using the LAC regimen has decreased in the last years. The LACE regimen has been associated with an increased eradication rate but can reach to statistically significance. Further studies BIBF 1120 with larger cohorts are needed to examine the success of the LACE regimen for H. pylori eradication.”
“Mesenchymal neoplasms of the vulvovaginal and inguinoscrotal regions are among the most diagnostically challenging specimens in the pathology laboratory owing largely to their unique intersection between general soft tissue tumors and relatively genital-specific mesenchymal tumors. Genital stromal tumors are a unique

subset of soft tissue tumors encountered at this location, and this group includes fibroepithelial stromal polyp, Galardin superficial (cervicovaginal) myofibroblastoma, cellular angiofibroma, mammary-type myofibroblastoma, angiomyofibroblastoma and aggressive angiomyxoma. Aside from the striking morphologic and immunophenotypic similarity that is seen with these entities, there is evidence that a subset of genital stromal tumors may be linked genetically. This review will focus on simplifying this group of tumors and provide the pathologist or dermatopathologist with practical management information. Smooth muscle tumors of the external genitalia will also be discussed.”
“Treatment with the chemotherapeutic agent oxaliplatin produces a robust painful neuropathy similar to various other neuropathic VX-770 manufacturer conditions which result in loss of nerve fibers innervating the skin. This loss of intraepidermal nerve fibers (IENFs) appears to play an important role in neuropathy, but has yet to be investigated in oxaliplatin-induced

neuropathic pain. For this study, mechanical hyperalgesia and IENF density were measured in rats receiving oxaliplatin, given at a dosage of 2 mg/kg every other day for four injections. The immunomodulatory agent minocycline (25 mg/kg) was also administered and was given 24 h prior to the first dose of oxaliplatin and continued throughout oxaliplatin treatment. Immunohistochemistry using the pan-neuronal marker PGP9.5 was used to investigate IENF densities in hind paw skin on Day 15 and Day 30. The results show that a robust mechanical sensitivity developed in oxaliplatin treated animals, as did a pronounced decrease in epidermal nerve fibers, and these outcomes were effectively prevented by minocycline treatment. This is the first study to show changes in IENF density in oxaliplatin treated animals, and confirm not only a relationship between IENF loss and hypersensitivity but also prevention of both with minocycline treatment (C) 2011 Elsevier Inc. All rights reserved.

Applications signaling pathway were designed modularly and can be used standalone. These tools are written in Perl and Python programming languages and are supported on Windows platforms. They are all released under an Open Source Software license and can be freely downloaded from our software repository hosted at GoogleCode.”
“In this work, we report that Entpd1(-/-) mice, deficient for the ectonucleotidase nucleoside triphosphate

diphosphohydrolase-1 (NTPDase1), produce smaller litters (27% reduction) compared with wild-type C57BL6 animals. This deficit is linked to reduced in vivo oocyte fertilization by Entpd1(-/-) males (61 +/- 11% versus 88 +/- 7% for Entpd1(-/-)). Normal epididymal sperm count, spermatozoa morphology, capacitation, and motility and reduced ejaculated sperm number (2.4 +/- 0.5 versus 3.7 +/- 0.4 million for Entpd1(-/-)) pointed to vas deferens dysfunction.

NTPDase1 was localized by immunofluorescence in the tunica muscularis of the vas deferens. Its absence resulted in a major ATP hydrolysis deficiency, as observed in situ by histochemistry and in primary smooth muscle cell cultures. In vitro, Entpd1(-/-) vas deferens displayed an exacerbated contraction to ATP, a diminished response to its non-hydrolysable analog alpha beta MeATP, and a reduced contraction to electrical field stimulation, suggesting altered P2X1 receptor function with a propensity to desensitize. This functional alteration was accompanied by a 3-fold decrease in P2X1 protein expression in Entpd1(-/-) vas deferens with no Ulixertinib variation in mRNA levels. Accordingly, exogenous nucleotidase activity was required

ZD1839 datasheet to fully preserve P2X1 receptor activation by ATP in vitro. Our study demonstrates that NTPDase1 is required to maintain normal P2X1 receptor functionality in the vas deferens and that its absence leads to impaired peristalsis, reduced spermatozoa concentration in the semen, and, eventually, reduced fertility. This suggests that alteration of NTPDase1 activity affects ejaculation efficacy and male fertility. This work may contribute to unveil a cause of infertility and open new therapeutic potentials.”
“Affecting more than 230,000,000 patients, diabetes mellitus is one of the most frequent metabolic disorders in developed countries. Among other complications, diabetic patients have an increased fracture risk and show delayed fracture healing. During the disease progression, these patients’ blood glucose and insulin levels vary significantly. Thus, the aim of this study was to analyze the effects of glucose and insulin on primary human osteoblasts. Although, in the presence of insulin and glucose, proliferation of osteoblasts was increased (1.2- to 1.7-fold), their alkaline phosphatase activity and, consequently, production of mineralized matrix were significantly reduced down to 55 % as compared to control cells (p < 0.001).