von Hippel (1) and A. Lindau (2) early in the 20th century. It is a rare highly penetrant autosomal dominant genetic predisposition to malignant and benign tumors, emanating from over 1,000 possible mutations in the VHL tumor suppressor gene on chromosome 3p25. how to order However, approximately 20% of these mutations occur de novo (3). It is typically sellekchem associated with central nervous system hemangioblastomas, clear renal cell carcinomas, cystadenomas, and neuro-endocrine tumors depending on the sub-type (4). Patients with VHL type I usually manifest hemangioblastomas but rarely present with clear renal cell carcinoma or pheochromocytoma. On the Inhibitors,research,lifescience,medical other hand, patients with VHL type II comprises

sub-types A, B, and C, which predispose to the development of hemangioblastoma; hemangioblastomas and clear renal cell carcinoma; and pheochromocytomas; respectively (4). The rarely observed VHL type III is associated with Chuvash polycythemia. Pancreatic serous cystadenomas Inhibitors,research,lifescience,medical are entail a relatively rare VHL presentation, affecting only ~10% of patients (5). Further rarely, the above

mentioned patient sub-population develops Inhibitors,research,lifescience,medical hepato-biliary obstruction requiring decompression (6). In the presented case, the pancreatic serous cystadenomas (Figure 1) was unresectable as per the extent of the disease and the concomitant portal hypertension. Yet, a suitable palliative alternative was de rigueur. Percutaneous cholecytostomy tube (PTC) would transiently palliate hepato-billiary, but would not alleviate gastric outlet obstruction. PTC is inconvenient in a functional patient with favorable prognosis. Duodenal stent option was limited by the distorted anatomy and would not resolve the biliary obstruction. Ideally, this patient would require

a choledocho- (or haepatico-) jejunostomy and a gastro-jejunostomy Inhibitors,research,lifescience,medical fashioned on a single limb or through a Roux-en-Y reconstructive bypass. Nevertheless, extensive portal-hypertension Inhibitors,research,lifescience,medical secondary to occlusion of the portal vein and the subsequent development of varices at the level of the hepatoduodenal ligament would render this surgical option unnecessarily risky, if not unwantedly GSK-3 morbid. Along the same line, any laparoscopic approach would be discouraging. As a result, a cholecysto-jejunostomy (in addition to a gastro-jejunostomy) was performed. Currently, this procedure turned into a mere historical curiosity—it is performed only as a last resort, and most often in the developing world where resources are scarce, expertise is scant, and patients generally present with advanced disease (7). However, this procedure constitutes a safe and effective last-resort in the hepato-billiary armamentary. Undoubtedly, the surgical procedure described above does not treat portal hypertension. But since the patient remains asymptomatic, neither a surgical shunt nor a trans-jugular intra-hepatic systemic shunt is currently indicated. It is hard to explain the uncontrolled hyperglycemia experienced by the patient.

Another possible explanation is that the relationship between OSAS and depression is indirect, mediated by a correlate of OSAS, such

as obesity. Together with age, obesity is the strongest risk factor for the development of OSAS.92-97 Obese individuals suffer body image dissatisfaction, discrimination, and psychosocial distress,98 and several studies have shown an increased prevalence of depression among obese subjects.99-101 The degree to which the severity of apnea and obesity contribute to the relationship between depressive Pazopanib FGFR symptoms and OSAS has recently been explored by Aloia et al.73 They found that depressive Inhibitors,research,lifescience,medical symptoms that are predominantly associated with Inhibitors,research,lifescience,medical the somatic dimension of depression (such apathy, loss of energy, and irritability) were more strongly associated with apnea severity, whereas depressive symptoms associated with the cognitive dimension of depression (pessimism, feeling of failure, and self-dislike) were more strongly associated with obesity. In addition, gender appears to influence these relationships, since men and women with apnea manifest depressive symptoms differently. Men only showed a relationship between apnea severity Inhibitors,research,lifescience,medical and somatic complaints,

and women only showed a relationship between obesity and the cognitive factor of depression. Pillar and Lavie68 also found gender differences in the clinical manifestations of OSAS, with Inhibitors,research,lifescience,medical women selleck screening library scoring higher on depression and anxiety scales than men, independently of other factors. Those studies serve to stress the likely Inhibitors,research,lifescience,medical complex nature of the relationship between depression and OSAS, and highlight the multiple potential etiologies of mood disorders in these patients. RLS and PLMS RLS is a condition in which patients at rest, especially in the evening and during the night, Carfilzomib report leg paresthesias

accompanied by an urge to move their legs. According to the International Restless Legs Syndrome Study Group102 obligatory features are: (i) a desire to move the extremities associated with discomfort; (ii) motor restlessness; (iii) worsening of symptoms at rest with relief with movement; and (iv) worsening of symptoms later in the day or at night. Up to 80% of patients with RLS present PLMS,103 and this phenomenon is considered to be a supportive criteria for the diagnostic of RLS. PLMS appears as repetitive episodes of muscle contraction, 0.5 to 5 s in duration, separated by intervals of 5 to 90 s.104 Isolated PLMS may also occur without complaints of RLS, leading to the diagnosis of PLMD.

Unlike in the hourglass

arena, in circular arenas there is no requirement for flies to make large-angled turns to follow the wall because the arena walls are concave. In circular arenas, the effect of the curved walls on the turn angle is clearly inhibitor order us evident in the shift of the peak of the turn angle from 0° to 12° in the turn angle distribution in the boundary zone. Hence, small turn angle movement is not driving the wall-following behavior rather it is wall-following behavior that shapes Inhibitors,research,lifescience,medical the turn angles made by flies. Exploration of boundary Our data strongly suggest that the boundary of a circular arena is a primary object of exploration, as demonstrated by the ability of high-contrast walls to rescue the w1118 attenuation of exploration deficit. It remains possible however

that the w1118 initial activity attenuation phenotype is not primarily due to poor visual acuity. Mutations in white are pleiotropic, resulting in defects in vision and also reduced levels of dopamine, Inhibitors,research,lifescience,medical serotonin, and histamine found with the Drosophila head (Borycz et al. 2008; Sitaraman et al. 2008). These biogenic amine reductions, in theory, may cause hyperactivity or learning deficits independent of visual exploration that could contribute to the w1118 activity attenuation phenotype (Sitaraman et al. 2008). The lower Inhibitors,research,lifescience,medical levels of dopamine found in the heads of the w1118 mutants is an unlikely source for the activity attenuation phenotype since reducing dopamine leads to lower levels of spontaneous activity (Liu et al. 2007; selleck kinase inhibitor Riemensperger et al. 2011). Nevertheless, we believe that the most straightforward explanation for these data is that similar to blind norpA7, glass2, and the white-eyed Inhibitors,research,lifescience,medical brown1, scarlet1 double mutant (Liu et al. 2007), the activity attenuation defect in w1118

is due to the poor visual acuity associated with this mutation. Although Inhibitors,research,lifescience,medical this is likely due to the absence of screening pigments in the eyes of the w1118 mutants, the visual defect may also result from the reduced histamine found within this genotype since this neurotransmitter is used by photoreceptor neurons (Hardie 1987). In either or both cases, the opaque boundary likely rescues this activity attenuation phenotype due AV-951 to the increased contrast it provides, allowing the w1118 mutants to detect the boundary and abrogate the novelty. In the concentric inner circle and the internal corner arenas, the flies were preferentially attending to the arena boundary and not just vertical walls. This suggests that there is a specific feature of the boundary that the flies attend. When the flies are actively exploring the arena boundary, they bypass shelter, suggesting this is not a primary goal for the exploration. Moreover, our turn angle calculations and hourglass experiments indicate that wall-following behavior shapes turn angles in the boundary zone and not vice versa.

Therefore, in group 1 it seems that dexamethasone delayed the re-epithelialization of the epithelium, induced keratocyte apoptosis and the upregulation of extracellular materials in the corneal stroma adjacent to the epithelial defect, and increased stromal changes and corneal haze. On the contrary, in group 3 corneal haze decreased compared with controls. Conclusion The findings of the present study shows that Inhibitors,research,lifescience,medical the association of 3% concentration of NAC and 0.1% concentration of dexamethasone immediately after corneal ulceration can delay corneal wound healing, and consequently produce more corneal

haze. Thus, the use of 0.1% concentration of dexamethasone should be delayed at least until the completion of the epithelial Cabozantinib FDA defects. Further studies with larger sample size are needed to confirm the findings of this study. Inhibitors,research,lifescience,medical Acknowledgment This study was supported by a research grant (84-VE-1781-C308) from the Research Council of Shiraz University. The authors would like to thank Dr Maryam Ansari for her assistance with the statistical analysis of the findings. Conflict of Interest: None declared
The amino groups of proteins, particularly the side chain of lysine, arginine, and histidine react non-enzymatically with reducing sugars. This post-translational modification called “glycation” or “maillard reaction”, leads via reversible Schiff-base adducts to protein bound amadori Inhibitors,research,lifescience,medical products.1-3 By subsequent oxidation

and dehydration, a broad range of brown heterogeneous Inhibitors,research,lifescience,medical products, mostly fluorescent with nitrogen- and oxygen- containing heterocyclic compounds, called advanced glycation end products

(AGEs) are formed. The formation of AEGs is irreversible, and causes a resistant protein deposition to protease.4,5 The Maillard reaction was first described by L.C. Maillard a chemist, who reported the formation of brown products upon heating a solution of amino acid (AA) and sugar.6 Schematic representation of the Maillard reaction (A) and structures of AGEs (B, C and Inhibitors,research,lifescience,medical D),7 are shown in figure 1. Pathological Consequences of AGEs In vivo Glycation modifies the structural properties of proteins such as albumin and haemoglobin leading to inflammation and oxidative stress. The pathological role of AGEs in diseases such as diabetes mellitus (DM) Dacomitinib is not fully understood. In addition to change of the protein structure, the receptor mediated mechanism of AGEs is of special interest.8 Figure 1 Schematic representation of the Maillard reaction (A) and structure of advanced glycation end products AGEs (B, C and D). The pathological features of AGEs, which are not receptor mediated, can be observed in the progression of cataracts. Evidence suggests that the glycation of lens protein is one of the causes of cataract,9 and is observed in long-lived proteins such as collagen and eye crystalline.10 However, the pivotal role of AGEs and the interaction with the receptor is not fully understood.

2007; Willems et al. 2009), even during nonmotor visuospatial mental operations, for example, mental rotations (Lamm et al. 2001). Interestingly, previous brain imaging studies have not reported MOT-related

activations in the temporal cortex that would resemble our findings. The superior temporal gyrus and sulcus have been associated Inhibitors,research,lifescience,medical with the attribution of animacy and mental states (Castelli et al. 2000). For instance, Schultz et al. (2004, 2005) used stimulus displays featuring abstract objects (geometrical shapes) that moved in an apparently self-propelled manner. The authors manipulated object “behavior” to give the impression of an “interaction” between two objects.

They found activations in the superior and middle temporal gyrus in association with a high the site degree of attributed intentionality. We found activation maxima similar Inhibitors,research,lifescience,medical to those reported by Schultz and colleagues (our maxima: 54/−55/13, −57/−19/4, 42/−28/10; Schultz et al. 2004: 48/−44/12, −60/−56/4, −56/−30/4; Schultz et al. 2005: 39/−57/22; −60/−27/9). However, with the current experimental design, we cannot determine whether or not our participants Inhibitors,research,lifescience,medical may have attributed animacy and/or intentionality to the moving objects. Thus, the significance of our JQ1 clinical trial findings remains to be resolved by future studies. In the following sections, we will focus our discussion on the activations in our area of interest, the frontal cortex. Dorsal and ventral premotor activations In accordance with our hypothesis, we found activation maxima in BA6 and BA44. We assume that these activations Inhibitors,research,lifescience,medical reflect the involvement of the dorsal and ventral premotor cortices (PMd, PMv). The following sections will reflect on this assumption from anatomical and functional perspectives. Importantly, premotor activations would be in line with the idea of recruitment of prediction processes during MOT. However, alternative

Inhibitors,research,lifescience,medical result interpretations will be addressed, namely processes of oculomotor control and visuospatial Dacomitinib attention as the source of DLFC activation. We will conclude with speculations regarding the functional implications of our findings. Functional boundaries of FEF versus PMd Based on our finding of activation in the DLFC, the important question arises whether this activation can be attributed to the PMd, possibly representing prediction processes as hypothesized, or whether it should be rather attributed to FEF involvement governing oculomotor control. As the PMd and the FEF are adjacent (or even overlapping) brain structures (Melamed and Larsen 1979; Petit et al. 1996; Schubotz and von Cramon 2001; Ptak and Schnider 2011), this question cannot be easily answered based on anatomical parameters. To tackle this issue, we implemented the FEF-L, as described above.

Dioleoylphosphatidylethanolamine (DOPE), a neutral lipid, is often used in conjunction with cationic DAPT secretase Sigma lipids because of its membrane destabilizing effects at low pH, which aide in endolysosomal escape [26]. Many cationic lipid compounds

have been formulated since the advent of DOTMA [27–31]. Each lipid has different structural aspects, such as head group size and Vandetanib hydrocarbon tail length. These aspects confer distinct characteristics to the lipid/DNA complex, which in turn affect association with and uptake into the cell. However, the basic structure of cationic lipids Inhibitors,research,lifescience,medical mimics the chemical and physical attributes of biological lipids [32]. The positive charge on the head group facilitates spontaneous electrostatic interaction with DNA, as well as binding of the resulting lipoplexes to the negatively charged components of the cell membrane prior to cellular uptake [33, 34]. The use of a cation is a recurring theme for virtually Inhibitors,research,lifescience,medical all chemically mediated gene Inhibitors,research,lifescience,medical delivery vectors, including polymers, lipids, and nondegradable nanoparticles. Between 8–18 carbons commonly comprise the hydrocarbon tails of lipids used for gene delivery. The tails are typically saturated, but a single double bond is occasionally seen. The combination

of hydrocarbon chains in a lipid mixture can be symmetric or asymmetric. It has been shown that certain asymmetric lipid mixtures with both shorter saturated carbon Inhibitors,research,lifescience,medical chains and long unsaturated carbon chains produce relatively high transfection efficiencies as compared to mixed formulations of symmetric cationic lipids [35]. Hydrophobic tails are not the only liposomal features that play a role in effective gene delivery—ionizable head groups are also involved. Some examples are the

multivalent cationic lipids DOSPA and DOGS (covered in Section 3.2); both of which have a functionalized spermine head group that confers the ability to act as a buffer, such as in the case where there is an influx of protons Inhibitors,research,lifescience,medical into a maturing endosome/endolysosome Anacetrapib [36]. Such buffering could extend the amount of time needed to activate acid hydrolases and could explain why some multivalent cationic lipids can exhibit higher transfection efficiencies versus their monovalent counterparts [25, 37]. 3.1. Monovalent Cationic Lipids 3.1.1. DOTMA (see Figure 3) Figure 3 The structure of DOTMA. N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethylammonium chloride, or DOTMA, was one of the first synthesized and commercially available cationic lipids used for gene delivery. Its structure consists of 2 unsaturated oleoyl chains (C18:Δ9), bound by an ether bond to the three-carbon skeleton of a glycerol, with a quaternary amine as the cationic head group [22].

88 The differential regulation of those three miRNAs during HF possibly facilitates the extensive ECM remodeling observed in the myocardium (see also 75,87,89 ). Other studies have pinpointed miRNAs related to HF-associated pathologies, such as hypertrophy,

HCM, DCM and ICM. In specific, AUY922 NVP-AUY922 studies in left ventricular tissue acquired from HCM patients revealed increased expression of miR-221, which was also upregulated in the hypertrophic (2 weeks) and failing hearts (9 weeks) of TAC mice. Further studies in rat CMCs demonstrated that forced expression of miR-221 by miRNA mimics is capable of inducing hypertrophy and re-expression of fetal genes in vitro, whilst knockdown of endogenous miR-221 abolished these effects. Moreover, in silico target prediction and experimental assays indicated that miR-221 possibly acts via targeting the suppressor of cardiac hypertrophy p27. 90 MiR-499 upregulation in human hypertrophied and failing hearts was associated with decreased expression of an array of predicted targets. Interestingly, studies in mice showed that miR-499 suffices for the induction of HF and acceleration of the pathological remodeling, upon pressure

overload. AKT and MAPKs were amongst the miR-499 numerous targets, while miR-499- induced cardiomyopathy was associated with changes in protein phosphorylation (e.g. HSP90, PP1α), thus revealing a spectrum of putative mechanisms via which miR-499 may contribute to cardiac pathophysiology. 13 Of particular interest is also the upregulation of miR-24 in cardiac tissue of ICM and DCM-related HF, which seemingly accounts for the under-expression of junctophilin 2 (JP2). JP2 is a structural protein that anchors the sarcoplasmic reticulum (SR) to the transverse tubules (TT) of the plasma membrane, which are the major sites of the excitation–contraction coupling. Importantly, transmission electron microscopic imaging revealed a significant reduction in SR-TT junctions in the ICM and

DCM specimens, indicating that miR-24 and JP2 dysregulation may ultimately lead to defective excitation-contraction Carfilzomib coupling, a characteristic of failing CMCs. 91 Examples of miRNAs associated with age-related HF include the downregulated miR-18a, -19a and -19b leading to upregulation of the ECM proteins CTGF and TSP1, possibly in the context of ECM remodeling during HF pathogenesis. 77 miRNAs signatures in animal models of HF miRNAs signatures during the development of cardiac pathologies preceding HF: A close up in hypertrophy Besides investigations in human HF, a series of animal model studies, predominantly involving transverse aortic constriction (TAC), have provided valuable insights into the miRNA expression alterations contributing to pathogenesis of hypertrophy and HF.

2012) as specified by the manufacturer (see the technical information data sheet). Cytochrome oxidase (CO) staining Two rats were used to verify the possibility of using the technique in this series of experiments. Animals were perfused and tissues postfixed and cut as described

above. Brains were freeze sectioned in the sagittal plane. Two consecutive sections, one per stereotaxic plane, were used in two different ways. The first sections (60 μm thick) were incubated at 37°C in the dark for 10–12 Inhibitors,research,lifescience,medical h in a solution containing 50 mg DAB, 30 mg cytochrome C (Type III, Sigma), and 4 g sucrose dissolved in 90 mL PB (0.1 mmol/L, pH 7.4; Wong-Riley 1979). Incubation was arrested when a clear differentiation between cerebral cortex and cc was visible. Sections were rinsed many times in PB, mounted on subbed slides, air-dried, dehydrated Inhibitors,research,lifescience,medical in xylene and then

coverslipped. The adjacent sections (40 μm thick) were counterstained with neutral red (1% in aqueous solution) and then coverslipped. Selected sections from CC-NADPH-1/11, CC-nNOS-1/6 and CC-Fl-1 and -2 were used for CO staining as described above. Data analysis The distribution of NADPH-d+ Inhibitors,research,lifescience,medical and NOSIP neurons in the cc was obtained using a camera lucida attached to a Leitz Orthoplan microscope equipped with a 25× objective. Callosal boundaries were obtained by comparing the sections reacted for COHi with those counterstained with neutral red. The reconstructions thus obtained were

then compared with those of the atlas of Paxinos Inhibitors,research,lifescience,medical and Watson (1982). Counts were performed in serial sagittal sections from two animals (CC-NADPH-10-11; see Table ​Table2).2). The total number of intracallosal NADPH-d+ neurons was calculated on sections from both hemispheres starting from the lateral 4.5 sagittal plane of one hemisphere to reach Inhibitors,research,lifescience,medical the same stereotaxic plane in the contralateral hemisphere. Table 2 (A) Arbitrary subdivisions of the rat cc, (B) Number of NADPH-d+ neurons in the three subdivisions of the rat cc Microscopic studies of the morphology and percentage of intracallosal neurons (three cases: CC-NADPH-d-5; -7; -9; see Tables ​Tables3,3, ​,4)4) were Batimastat performed using staining criteria similar to those of previous Golgi and NADPH-d studies (Jacobs and Scheibel 1993; Jacobs et al. 1993; Phillips et al. 2000; Barrera et al. 2001). Selected neurons, drawn using a camera lucida and a 100× oil immersion objective, exhibited the following characteristics: (1) labeled neurons had a clearly selleck chemicals Gefitinib distinguishable morphology; (2) cell bodies had a central location within the 60-μm section depth to minimize the cutting of dendritic branches near the section surface; (3) dendrites were not overly obscured by other heavily stained processes from nearby cells; (4) dendritic trees were intensely labeled and did not show discontinuity with their cell bodies.

For this reason, both standard deviations given by a plane and by a curved surface are separately reported in the results.Finally, the resolution has been estimated differently along the optical axis of each range device (z) and along the other two directions (xy). These two resolution parameters will be indicated hereafter as z resolution and horizontal resolution respectively. One key point of the proposed approach for resolution estimation consists in representing the range images associated with each 3D device as grey level images on which the analyses previously developed for the 2D imaging area can be applied. For example, if a black to white transition has to be replicated, the corresponding 3D target will be characterized by an abrupt jump of its 3D surface along the z direction, and the range device will be oriented in order to have
Among piezoelectric materials, Lead Lanthanum Zirconate Titanate (PLZT) is one of the most popular.

PLZT is a ferroelectric solid solution with wide-ranging material properties that depend on its composition [1]. Recently, a new PLZT bulk single plate, called selleck chem ceramic-controlled piezoelectric (CCP) has been produced; this CCP has a 300 ��m Pt-wire implant in order to form a free upper face that measures optic and mechanic events [2]. This structure design includes a modified electrode configuration: a Pt-wire introduced into a bulk PLZT. The Pt-wire was chosen as an implant because it possesses high resistance to chemical attack, it has excellent high-temperature characteristics (melting point 1,768.

3 ��C), and it has stable electrical properties and thermal conductivity with small variations [3]. When CCP is polarized, the mobile charges in the Pt-wire accumulate on its surface until the field produced completely cancels the external field applied to the conductor; this results in electrical equilibrium within the Pt-wire so the internal the electrical field is zero, as shown in Figure 1. This means that the net charge is distributed over a section of the surface, which has a thickness of several atomic layers, but not in the geometrical sense [4]. The sample preparation is described in the following sections [2].Figure 1.Electric field waves across Pt-wire (top view).The Pt-wire cylinder dimensions are 10 mm high and 0.3 mm diameter; this gives a surface area of 9.42 mm2. The surface area of one of the faces of the ceramic is 78.53 mm2, making the surface area of the ceramic 8.33 times bigger than that of the Pt-wire.Pt-wire implanted into bulk PLZT ceramic behaves singularly in the CCP due to the domains coating the Pt-wire, as shown in Figure 2.

The miR-195 transgenic animals developed

pathological cardiac hypertrophy and HF, thus revealing a direct and sufficient role of miR-195 in the development of HF in mice. Mir-24 transgenic mice died at the embryonic stage, whilst overexpression of mir-214 had no phenotypic effect. Similarly, Ucar CYP450 inhibitor et al investigated the role of miR-212 and -132, also upregulated during hypertrophy in the heart of TAC mice. 103 Transgenic mice with cardiac specific overexpression of miR-212 and -132 presented with hypertrophic hearts, exhibited signs of severe HF and experienced premature death. In vitro experiments from the same group showed that miR-212 and -132 target the anti-hypertrophic TF Foxo3a, whilst overexpression of miR-212 and -132 results in hyperactivation of pro-hypertrophic calcineurin/NFAT signaling. 103 MiR-23a levels have also been found elevated in rodent models of hypertrophy,

and specifically upon isoproterenol-induced cardiac hypertrophy in mice, 80 as well as pressure overload-induced hypertrophy in both mice and rats. 93 In order to elucidate its role, Wang et al produced transgenic mice with cardiac overexpression of miR-23a, which presented with exaggerated hypertrophy upon phenylephrine (PE) treatment or pressure overload induced by TAC. 81 This study also reported that endogenous miR-23a was upregulated by hypertrophic stimuli (PE, endothelin, ET) in cultured CMCs, thereby indicating that miR-23a participates in the transduction of the hypertrophic signal. Moreover, they identified the anti-hypertrophic Foxo3a as a target of miR-23a, and showed that miR-23a and Foxo3a bi-transgenic mice present with an attenuated hypertrophic response, in comparison to the miR-23a transgenic mice alone. 81 Interestingly, in vitro studies by other teams revealed additional molecular players in the putative miR-23a pro-hypertrophic machinery. Specifically, experiments in CMCs showed that the nuclear

factor of activated T cells 3 (NFATc3) induces miR-23a, which in turn targets the negative regulator of hypertrophy muscle ring finger1 (MuRF1) Batimastat thereby triggering cardiac hypertrophy (Figure 2). 80,104 Figure 2. The role of miR-132, -212 and -23a in molecular pathways of cardiac hypertrophy. Activation of calcineurin/NFAT pro-hypertrophic pathway leads to increased expression of miR-23a. MiR-23a targets the negative regulator of hypertrophy muscle ring finger1 … Mir-27b has been seen upregulated in cardiac hypertrophy, and specifically in the cardiac-specific Smad4 knockout mouse model. 105 Importantly, cardiac-specific overexpression of miR-27b in transgenic mice was sufficient to induce hypertrophy and heart dysfunction, 105 thereby implying a direct association.