[Diagnostic value of FCGR1B gene transcription level in active tuberculosis].

Objective: To investigate the diagnostic potential of Fc fragment of IgG receptor 1b gene (FCGR1B) transcription level in active tuberculosis. Methods: From February to September of 2018, we collected peripheral blood from patients with active tuberculosis, latent tuberculosis infection (LTBI), cured patients with tuberculosis, healthy people and patients with pneumonia in the Eighth Medical Center of PLA General Hospital. Peripheral blood mononuclear cells (PBMCs) were isolated for total RNA extraction and cDNA synthesis. The expression of FCGR1B mRNA in PBMCs was detected by quantitative real-time PCR (QPCR). Nonparametric test was used to compare the differential expression of FCGR1B mRNA between patients with active tuberculosis and control groups, and the relationships between FCGR1B mRNA expression and patient's illness condition and inflammatory indexes were analyzed by Correlation analysis. The potential of FCGR1B mRNA as a diagnostic marker for active tuberculosis was evaluated by receiver operating characteristic curve (ROC) analysis. Results: The expression of FCGR1B mRNA in PBMCs from patients with active tuberculosis was significantly increased when compared with non-tuberculosis controls, including individuals with LTBI, healthy people, cured patients with tuberculosis and patients with pneumonia (u=2 081, P<0.001). The expression of FCGR1B mRNA was higher in patients with tuberculosis who had more bacteria(H=12.35, P=0.015), and was correlated with the C-reactive protein (CRP) (r=0.30, P=0.008). ROC analysis showed that FCGR1B mRNA could distinguish active tuberculosis from non-tuberculosis with area under curve (AUC) of 0.849. The sensitivity and specificity were 71.43% and 84.17% respectively. The AUC of FCGR1B mRNA in distinguishing extra-pulmonary tuberculosis from controls was 0.906. The sensitivity and specificity were 84.62% and 91.89%, respectively. Conclusion: FCGR1B mRNA is a potential molecular marker for diagnosis of active tuberculosis.

Gluconacetobacter sp. gel_SEA623-2, bacterial cellulose producing bacterium isolated from citrus fruit juice.

Cellulose producing bacterial strain was isolated from citrus fruit juice fungus. The isolated strain was identified as Gluconacetobacter sp. gel_SEA623-2 based on several morphological characteristics, biochemical tests, and 16S rRNA conducted. Culture conditions for bacterial cellulose production by SEA623-2 were screened in static trays. Conditions were extensively optimized by varying the kind of fruit juice, pH, sugar concentration, and temperature for maximum cellulose production. SEA623-2 has a high productive capacity in citrus processing medium, but not in other fruits. The optimal combination of the media constituents for bacterial cellulose production is as follows: 10% citrus juice, 10% sucrose, 1% acetic acid, and 1% ethanol at 30 °C, pH 3.5. Bacterial cellulose produced by SEA623-2 has soft physical properties, high tensile strength, and high water retention value. The cellulose produced by the selected bacteria is suitable as a cosmetic and medical material.

[Jinghuaweikang capsules combined with furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori infection: a multicenter randomized controlled clinical trial].

Objective: To explore the efficacy of Jinhuaweikang capsules plus furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori (H.pylori) infection. Methods: This is a prospective randomized controlled multicenter clinical trial. Patients with chronic gastritis from H. pylori infection in whom eradication treatment failed were recruited from 6 hospitals. All patients were divided into 4 groups using stratified randomization: group A1 (PAFJ), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ Jinghuaweikang 3 capsules, twice a day for 10 d (d1-10); group A2, PAFJ therapy as in group A1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28); group B1 (PAFB), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ bismuth potassium citrate 220 mg, twice a day for 10 d (d1-10); group B2, PAFB therapy as in group B1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28). At least 28 days after the end of treatment, all patients underwent 13C urea breath test for assessment of H. pylori eradication. Results: A total of 357 patients, 145 males and 212 females, were recruited, including 90 in group A1, 88 in group A2, 89 in group B1, and 90 in group B2. The eradication rates of H. pylori in groups A1 and A2 were 76.1%(67/88)and 79.6%(70/88) in per-protocol (PP) analysis, 74.4%(67/90) and 79.6%(70/88)in intention-to-treat (ITT) analysis; the rates in groups B1 and B2 were as 85.9%(73/85) and 92.1%(81/88) in PP analysis, 82.0%(73/89) and 90.0%(81/90)in ITT analysis. There were statistically significant differences in PP eradication rates among the 4 groups (P=0.020); there was statistically significant difference between groups A1 and B2, and also between groups A2 and B2 (P=0.003, 0.020), but not between groups A1/A2 and B1 (P>0.05), nor between groups B1 and B2 (P>0.05). No statistically significant differences in ITT eradication rates were found among the 4 groups (P>0.05). The improvement of belching and poor appetite for patients in groups A2 and B2 was better than those in groups A1 and B1. Conclusions: The efficacy of Jinghuaweikang capsules plus furazolidone-based quadruple therapy is superior to combination with furazolidone-based triple therapy as the rescue treatment of H. pylori, and superior to bismuth-containing quadruple therapy. Extending administration of Jinghuaweikang capsules to 28 days may better improve symptoms of indigestion.

Methyl jasmonate inhibits lipopolysaccharide-induced inflammatory cytokine production via mitogen-activated protein kinase and nuclear factor-κB pathways in RAW 264.7 cells.

Methyl jasmonate is an important signaling molecule involved in plant defense as well as in the regulation of plant growth and development. Despite its various functions in plants, its effects on animal cells have not been widely studied and no report has been issued on the molecular aspects of its anti-inflammatory effect. In the present study, we investigated the in vitro anti-inflammatory properties of methyl jasmonate in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Methyl jasmonate treatment effectively inhibited LPS-induced production of pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6) in a concentration-dependent manner. Furthermore, it attenuated the LPS-induced activation of nuclear factor-κB (NF-κB) by suppressing the degradation of the inhibitor of κB-α (IκB-α). Additionally, methyl jasmonate dose-dependently blocked the phosphorylation of mitogen-activated protein kinases (MAPKs), i.e., p38 kinase, extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK), in these cells. These results suggest that methyl jasmonate attenuated the LPS-induced release of pro-inflammatory mediators and cytokines by suppressing the activation of MAPK (JNK, ERK and p38) and NF-κB signaling. This study not only demonstrated that methyl jasmonate exerts anti-inflammatory activities in macrophages but also revealed its potential as a candidate for the treatment of various inflammation-associated diseases.

High-resolution anorectal manometry in newborns: normative values and diagnostic utility in Hirschsprung disease.

BACKGROUND: Conventional methods of screening for Hirschsprung disease (HD) in newborns (barium enema, BE; anorectal manometry, ARM; rectal suction biopsy, RSB) have limitations and/or are invasive. High-resolution anorectal manometry (HR-ARM) is a minimally invasive technique that has potential to overcome most of these limitations, but normative data and performance characteristics have not been reported in newborns. The aims of our study were to assess anorectal sphincter metrics including resting pressure (RP), anal canal length (ACL), and rectoanal inhibitory reflex (RAIR) in healthy and asymptomatic newborns, and to explore the role of HR-ARM in the diagnosis of HD using these normal parameters. METHODS: All procedures were performed using solid state HR-ARM equipment (Medical Measurement Systems, Enchede, The Netherland) by a single operator. In the first phase, 180 asymptomatic newborns (term newborns 95, preterm newborns 85) were studied, and anal RP, ACL, and RAIR were measured. In the second phase, 16 newborns with clinical manifestations of HD were studied (9 of whom had histopathologic confirmation), and parameters compared to asymptomatic newborns. KEY RESULTS: Normative RP values were higher in term newborns compared with preterm newborns (p < 0.05), and correlated with age. Progressive maturation of the anal sphincter was evident with chronologic age, both in preterm and term newborns. RAIR was present in all normal subjects. Using absent RAIR as indicative of HD, HR-ARM had a sensitivity 89% and specificity of 83% compared to RSB; these performance characteristics were better than BE (sensitivity 78%, specificity 17%), with significantly higher diagnostic accuracy (80% vs 53%, respectively, p = 0.009). CONCLUSIONS & INFERENCES: Anorectal sphincter pressure progressively matures with incremental increase in RP during the first months of life. HR-ARM is an effective and safe method that complements the diagnosis of HD in newborns.

Cycloastragenol is a potent telomerase activator in neuronal cells: implications for depression management.

Cycloastragenol (CAG) is an aglycone of astragaloside IV. It was first identified when screening Astragalus membranaceus extracts for active ingredients with antiaging properties. The present study demonstrates that CAG stimulates telomerase activity and cell proliferation in human neonatal keratinocytes. In particular, CAG promotes scratch wound closure of human neonatal keratinocyte monolayers in vitro. The distinct telomerase-activating property of CAG prompted evaluation of its potential application in the treatment of neurological disorders. Accordingly, CAG induced telomerase activity and cAMP response element binding (CREB) activation in PC12 cells and primary neurons. Blockade of CREB expression in neuronal cells by RNA interference reduced basal telomerase activity, and CAG was no longer efficacious in increasing telomerase activity. CAG treatment not only induced the expression of bcl2, a CREB-regulated gene, but also the expression of telomerase reverse transcriptase in primary cortical neurons. Interestingly, oral administration of CAG for 7 days attenuated depression-like behavior in experimental mice. In conclusion, CAG stimulates telomerase activity in human neonatal keratinocytes and rat neuronal cells, and induces CREB activation followed by tert and bcl2 expression. Furthermore, CAG may have a novel therapeutic role in depression.

INCB018424 induces apoptotic cell death through the suppression of pJAK1 in human colon cancer cells.

Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated the role of JAKs in colorectal cancer in order to develop effective therapeutic targets for INCB018424, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of INCB018424 on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. INCB018424 inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. INCB018424 causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow INCB018424-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by INCB01424 results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility.

Dysregulation of miR-106a and miR-591 confers paclitaxel resistance to ovarian cancer.

BACKGROUND: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. METHODS: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. RESULTS: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. CONCLUSION: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.

Symptomatic diffuse esophageal spasm as a major ictal manifestation of post-traumatic epilepsy: a case report.

Post-traumatic epilepsy (PTE) can create diagnostic confusion when typical epileptic seizures are not manifest. Abdominal symptoms as a manifestation of PTE are rare in this setting. We present a 43-year-old female with paroxysmal chest and abdominal pain, nausea, salivation, and intermittent dysphagia. Esophageal testing demonstrated diffuse esophageal spasm, but smooth muscle relaxants provided no relief. Finally, after history revealed that a motor vehicle accident temporally preceded symptom onset, video electroencephalography confirmed PTE. Therapy with anti-epileptic drug completely resolved symptoms, and the esophageal motor pattern normalized. We speculate that abnormal epileptiform discharges from the seizure focus altered cerebral input to intrinsic esophageal innervation, resulting in inhibitory dysfunction and a picture resembling diffuse esophageal spasm. This is the first report of symptomatic esophageal spasm as a major ictal manifestation of PTE.

Using ozonation and amino acids to change pasting properties of rice starch.

In this study, the effects of ozonation and the addition of amino acids on rice starches were determined in terms of pasting properties using a rapid visco-analyzer. Results from viscosity analysis showed that 30-min ozone treatment on commercial rice starch exhibited the greatest swelling extent among the treatments and least retrogradation tendency. The control pure oxygen treated sample had the best cooking stability. The addition of lysine (6%) to 30-min ozonated commercial rice starch significantly reduced peak viscosity (PV), minimum viscosity (MV), and final viscosity (FV) by 918, 1024, and 1023 cP, respectively. Moreover, it decreased Ptime, resulting in the faster swelling upon heating and less rigid gel formation upon cooling. Furthermore, the presence of lysine in 30-min ozonated starch isolate (WSI) also significantly reduced PV, MV, FV, pasting time, and total setback (TSB) and produced starch gel with the best cooking stability and the least retrogradation tendency. Ozonated starch exhibited similar pasting properties to those from oxidized starches treated with low concentrations of chemical oxidizing agents. The combination of lysine with ozonation resulted in pasting properties similar to starches treated with high levels of chemical oxidizing agents. The ozonated starch could be used as a thickening agent, whereas ozonated starch with lysine might be an alternative for a highly chemically oxidized starch. Therefore, ozonation alone or the combination of ozonation and addition of lysine might be used to develop new starch ingredients with various functionalities without using typical chemical modifications.

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis.

Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H(2)O(2), staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH(2)-terminal kinase (JNK) inhibitor, restored the level of Bcl-2 protein. Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway.

Down-regulation of claudin-2 in breast carcinomas is associated with advanced disease.

AIMS: Claudin 2 (CLDN2) is a family of integral membrane tight junctions. The aim was to determine the influence of CLDN2 expression on tumour behaviour and its role in breast carcinogenesis. METHOD AND RESULTS: Thirty-seven invasive breast carcinomas and corresponding normal breast tissues were examined for CLDN2 protein and mRNA expression using Western blotting and semiquantitative reverse transcriptase-polymerase chain reaction. The expression of CLDN2 protein in 118 cases of breast carcinoma was further studied with immunohistochemistry and related to various clinicopathological parameters. CLDN2 protein expression was significantly down-regulated (0.4-fold) in tumours compared with corresponding normal breast tissue (P < 0.0001). Down-regulation of CLDN2 was significantly associated with lymph node metastasis (P = 0.047) by Western blot analysis, and with high clinical stage (P = 0.040) by immunohistochemistry. The expression levels of CLDN2 mRNA in high clinical stages (stages II and III) were lower than those in low clinical stage (stage I) and normal tissue, but not statistically significantly so. CONCLUSIONS: These results suggest that CLDN2 is implicated in the progression as well as the development of breast carcinoma, indicating that CLDN2 is a possible tumour suppressor gene product.

Glycomics analysis of serum: a potential new biomarker for ovarian cancer?

We recently reported the use of matrix-assisted laser desorption ionization (MALDI) Fourier transformation mass spectrometry (FTMS) techniques to identify unique glycan markers in ovarian cancer cell lines which may be biomarkers for diagnosis of ovarian cancer. Glycan markers and CA125 levels are compared in a series of ovarian cancer patients and normal control subjects. Oligosaccharides (OS) were cleaved from the serum glycoproteins and isolated using solid phase extraction. MALDI-FTMS was then used to identify unique mass spectrometry (MS) peaks. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were calculated to measure the test performance of glycan markers. Sixteen unique OS MS signals were identified in ovarian cancer patient sera. Their additive mass/charge intensities were used to determine their presence or absence. The ovarian cancer patients varied in their disease status, with initial cancer stages ranging from IC to IV. Forty-four of 48 patients had detectable OS signals, with CA125 values between 2 and 17,044. Four patients had undetectable signals and their CA125 ranged between 7 and 10. Twenty-three of 24 control subjects had no detectable glycan markers, with CA125 levels between 10 and 64. Sensitivity and specificity values were determined to be 91.6% and 95.8%, respectively. The area under the ROC curve for all 72 samples was 0.954 (95% CI: 0.896, 1.0) using the glycomics assay, which was superior to CA125 in discriminating between cases and controls. This preliminary study suggests that glycomics profiling may be useful for the detection of ovarian cancer.

Thermal characteristics of ohmically heated rice starch and rice flours.

Thermal properties of conventionally and ohmically heated rice starch and rice flours at various frequencies and voltages were studied. There was an increase in gelatinization temperature for conventionally heated rice starches since they were pregelatinized and became more rigid due to starch-chain interactions. In addition, there was a decrease in enthalpy (energy needed) for conventionally and ohmically heated starches during gelatinization; thus, the samples required less energy for gelatinization during DSC analysis. Ohmically heated commercial starch showed the greatest decrease in enthalpy probably because of the greatest extent of pregelatinization through ohmic heating. Brown rice flour showed the greatest gelatinization temperature resulting from the delay of starch granule swelling by lipid and protein. Enthalpy of ohmically heated starches at 20 V/cm was the lowest, which was most likely due to the lower voltage resulting in a more complete pregelatinization from a longer heating time required to reach 100 degrees C. Ohmic treatment at 70 V/cm decreased onset gelatinization temperature of white flour; therefore, it produced rice flour that swelled faster, whereas the conventionally heated sample showed a better thermal resistance.

Targeted RNA interference of phosphatidylinositol 3-kinase p110-beta induces apoptosis and proliferation arrest in endometrial carcinoma cells.

Phosphatidylinositol 3-kinase (PI3K) signalling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumourigenesis. PI3K is overexpressed in many human cancers, including endometrial carcinomas, one of the most common female genital tract malignancies. Here, we used small interfering RNA (siRNA) targeted to PI3K p110-beta to determine whether inhibition of the beta isoform could be a potential therapeutic target for endometrial carcinoma. In this study, treatment of HEC-1B endometrial cancer cells with PI3K p110-beta-specific siRNA resulted in increased apoptosis and decreased tumour cell proliferation. Depletion of PI3K p110-beta decreased the protein levels of AKT1, AKT2, pAKT, and mTOR-downstream targets of PI3K. Knock-down of PI3K p110-beta by siRNA also induced decreased expression of cyclin E and Bcl-2, suggesting that PI3K p110-beta stimulates tumour growth, at least in part by regulating cyclin E and Bcl-2. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p110-beta may be a useful therapeutic strategy for endometrial cancers overexpressing PI3K p110-beta.

Inhibitory effects of Rumex japonicus Houtt. on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Rumex japonicus Houtt. (RJH) is one of the herbs used in Eastern countries for the treatment of atopic dermatitis (AD). It has been shown to have an antioxidative effect in human skin disease. OBJECTIVES: To examine whether RJH extract (RJH-E) suppresses the development of AD-like skin lesions in NC/Nga mice, which are induced by the repeated application of picryl chloride (PC). METHODS: The efficacy of RJH-E in NC/Nga mice was assessed by measuring symptom severity, scratching behaviour, Staphylococcus aureus numbers on an ear, and serum levels of IgE, interleukin (IL)-4 and interferon (IFN)-gamma. RESULTS: Oral administration of RJH-E to NC/Nga mice treated with PC inhibited the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores, and a decrease in hypertrophy, hyperkeratosis and infiltration of inflammatory cells in the skin. The scratching behaviour and numbers of S. aureus, which are known to be exacerbated in AD, were also significantly reduced by RJH-E. No significant change was observed in the serum levels of IFN-gamma, whereas IgE and IL-4 levels were significantly reduced by RJH-E. CONCLUSIONS: These results suggest that RJH-E inhibits the development of AD-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response. Our results indicate that RJH treatment could provide an effective alternative therapy for the management of AD.

Protein composition of the intranuclear inclusions of FXTAS.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. The pathologic hallmark of FXTAS is the ubiquitin-positive intranuclear inclusion found in neurons and astrocytes in broad distribution throughout the brain. The pathogenesis of FXTAS is likely to involve an RNA toxic gain-of-function mechanism, and the FMR1 mRNA has recently been identified within the inclusions. However, little is known about the proteins that mediate the abnormal cellular response to the expanded CGG repeat allele. As one approach to identify the protein mediators, we have endeavoured to define the protein complement of the inclusion itself. Fluorescence-activated flow-based methods have been developed for the efficient purification of inclusions from the post-mortem brain tissue of FXTAS patients. Mass spectrometric analysis of the entire protein complement of the isolated inclusions, combined with immunohistochemical analysis of both isolated nuclei and tissue sections, has been used to identify inclusion-associated proteins. More than 20 inclusion-associated proteins have been identified on the basis of combined immunohistochemical and mass spectrometric analysis, including a number of neurofilaments and lamin A/C. There is no dominant protein species in the inclusions, and ubiquitinated proteins represent only a minor component; thus, inclusion formation is not likely to reflect a breakdown in proteasomal degradation of nuclear proteins. The list of proteins includes at least two RNA binding proteins, heterogeneous nuclear ribonucleoprotein A2 and muscle blind-like protein 1, which are possible mediators of the RNA gain-of-function in FXTAS.