The FFT method from HREM images, on the other hand, provides LRO parameters in a small selected microscopic area, and therefore, it enables microscopic fluctuations of LRO parameters to be examined. Ordering maps from geometric ATM/ATR inhibitor clinical trial phase algorithm HRTEM images allow us to extract information on compositional variations and/or the state of deformation of the nanostructures by comparing the actual positions of the unit cells in the image with a reference lattice using such techniques as the peak pairs algorithm or geometric phase analysis [23, 24]. Even though these programs are mainly applied

to the analysis of the deformation present in the nanostructures, they can be used to perform other types of studies such as the spatial location of different phases and grains [25]. We follow a similar procedure here in order to obtain a spatial map of the distribution of the ordering. The procedure used for calculating the phase image, the Bragg filtered image and numerical moiré image using the GPA are as described by Hÿtch and co-workers [24, 26]. Briefly, the method consists of constructing a differential phase Selleckchem Aloxistatin map for a given Bragg region with respect to a reference lattice. In our case, we build numerical moiré images at position r, M(r), by superimposing the real lattice with a reciprocal lattice vector smaller than the average lattice where M is a magnification constant as [25, 27]: where g r is the

reference lattice in reciprocal space and u(r) is the displacement of the atomic column position from its nominal Astemizole position. Following this procedure, two translational moiré images (we used M = 1) are obtained using g r as the reference position of each (111) spot in the FFT pattern and a Bragg mask that includes the collinear ½(111) spot associated with the ordering arrangement. The final RGB multilayer reconstructed image is formed from the two inverse FFT (iFFT) images

of these selected masks. The spatial localization of ordering in each of the 111 planes is represented in the sets of red and green fringes. In order to improve visualization, a null matrix blue layer is used as background. The red and green fringes in this resultant image are consistent with the presence of ordering where the moiré spacing is proportional to 1/(g − gr). Results Photoluminescence In order to evaluate the optical emission efficiency, RT-PL measurements were carried out on both samples (Figure 1). Sample S100 showed a bimodal spectrum, with an emission peak at 1,108 nm and a distinct low wavelength shoulder feature at 980 nm. The main peak has a full width at half maximum (FWHM) of 79 meV. However, S25 showed only a single peak centred at 1,057 nm with a FWHM of 75 meV. The PL intensities were nominally identical to within the experimental error. Figure 1 Room-temperature PL spectra of MBE-grown GaAsBi layers. S25 (dashed) and S100 (solid) lines.

J Pharmacol Exp Ther 2004, 311: 1062–1070.CrossRefPubMed Competing interests The authors declare that they have no competing

interests. Authors’ contributions DS carried out the molecular genetic studies, participated in the cell culture and drafted the manuscript. GS carried out the drug sensitive analysis. GH participated learn more in the tests of internal irradiation with32P. JZ participated in the design of the study and performed the statistical analysis. EL conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript.”
“Introduction Hepatocellular carcinoma (HCC) is a frequent and lethal malignancy with high rate of metastasis, especially in some regions of Africa and Asia [1]. It ranks the sixth most common cancer of men and 11th one of women worldwide. There were more than half a million deaths per year. The number of new HCC cases occurring each year is almost equivalent

to the number of deaths [2, 3]. Since HCC is clinically silent at early stage, most HCC patients (> 80%) are presented with advanced Akt inhibitor or unresectable disease. Without treatment, the 5-year survival rate of HCC is less than 5%. To those with resected disease, the recurrence rate can be as high as 50% at 2 years and the 5 year survival rate is only 25–39%. Despite of the advances in treatment, the prognosis of HCC remains very poor due to the frequent presence of recurrence and the high rate of metastasis [3–5]. The programmed cell

death 4 (PDCD4) was found to be an inhibitor of neoplastic transformation. It was first found to be highly expressed during apoptosis, but the role of PDCD4 in programmed cell death was not clear. A comparative study on cells with different transformation response to tumor promoters revealed that PDCD4 was expressed more than ten folds higher in promotion-sensitive cells than in promotion-resistant cells. In less progressed mouse keratinocytes, see more higher level of PDCD4 was expressed [6]. Later investigations demonstrated that loss of PDCD4 expression was associated with tumor progression in carcinomas of the lung, colon, prostate, and breast [7]. The inhibition of PDCD4 on transformation is achieved through down-regulation of the JNK signal transduction pathway which is essential for cell migration. Decrease of JNK activity then leads to inhibition of cell migration [8, 9]. The metastasis tumor antigen 1 (MTA1) was originally identified by differential expression in rat mammary adenocarcinoma metastatic cells [10]. The expression of the MTA1 gene was found to be positively correlated with metastatic potential of some human cell lines and tissues, such as the breast, prostate, colon and pancreas [11–13].

2 Simplified BP Targets vs. the ‘Lower the Better’ The achieved level of SBP and DBP control is directly associated with the risk of cardiovascular (CV) disease (CVD) and stroke, across patient ages and ethnicities [9, 10]. Reducing the incidence of mortality and morbidity associated with CVD is linked to substantial socioeconomic and healthcare cost

savings [11]. Therefore, should BP targets be more aggressive than suggested in the latest 2013 ESH/ESC guidelines? The 2013 ESH/ESC recommendation for a BP target of <140/90 mmHg for most patients is based on a review of randomized controlled trial (RCT) data [12] that suggested a lack of evidence for a PLX4032 more aggressive, and previously recommended, BP target of <130/80 mmHg in patients with high CV risk [2]. However, the authors of the review state that despite scant evidence for lowering SBP below 130 mmHg in patients with diabetes or high/very high CV risk, a more aggressive approach may be prudent because antihypertensive therapy to

lower SBP to <130 mmHg appears well tolerated; they suggest more solid trial evidence should be gained [12]. Despite many major trials not achieving BP targets of <140/90 mmHg, there is a wealth of evidence to indicate a relationship between lower BP and reduced CV outcomes, suggesting further benefits are available from greater BP reductions. Certainly, in low-to-moderate risk patients https://www.selleckchem.com/products/Fulvestrant.html with uncomplicated hypertension, trial evidence supports that a reduction in SBP to <140 vs. >140 mmHg is associated with reduced adverse CV outcomes [13–15]. Other supportive evidence for intensive BP lowering in a range of patients is available, showing a lower risk of major CV events, especially stroke [16, 17] (Table 1). Law et al. performed a meta-analysis of data from randomized trials of BP-lowering therapy involving almost Thymidylate synthase half a million patients (with and without CVD), and observed substantial reductions in heart disease and stroke for a 10-mmHg reduction in SBP or a 5-mmHg reduction

in DBP, down to 110/70 mmHg [6]. A further meta-analysis of 32 randomized trials showed that reduction of SBP to 126 vs. 131 mmHg had the same proportional CV benefits as a reduction to 140 vs. 145 mmHg [18]. The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated significant reductions in the risk of a composite outcome of CV mortality, myocardial infarction (MI), and stroke following antihypertensive treatment down to a SBP of 134 mmHg [19]. Additionally, the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) trial (in patients with a history of stroke) revealed that the lowest follow-up BP levels (median 112/72 mmHg) were associated with the lowest risk of stroke recurrence, with progressively increased risk at higher BP levels [20].

cholerae O1/O139 cluster that are absent in non-toxigenic V. cholerae O1 isolates. Previous studies have shown the presence of non-toxigenic V. cholerae O1 strains in the environment and in humans [6, 18, 21, 27]. Serotyping is therefore not a reliable method for the identification of toxigenic and epidemic V. cholerae O1/O139 strains. Furthermore,

V. cholerae non-O1/O139 isolates have been described that are able to produce the cholera toxin but are not considered epidemic because only strains of serogroup O1/O139 and O37 are able to cause large outbreaks [6, 21, 27]. Thus, the presence of the ctxAB and tcpA genes is not the only prerequisite for epidemic potential. We have found that OmpU from epidemic V. cholerae has a unique and conserved amino acid sequence, which not only can be used in the presented BMN 673 MALDI-TOF selleck products MS assay, but also in a targeted PCR method. The difference in OmpU sequences between epidemic and non-epidemic isolates as well as the sequence variation among

non-epidemic strains raises the question of whether this variation is due to genetic drift or specific adaptation to different niches. From a DNA alignment of a 5,000 bp region surrounding the ompU gene of seven epidemic O1 and five non-toxigenic strains (Additional file 2: Figure S2), it became clear that the ompU gene has undergone a higher mutation rate compared to the surrounding genes and intergenic regions. This suggests that OmpU has been subject to selective pressure, possibly as a result of adaptation

to particular niches. A role for OmpU in host colonization has been proposed, potentially in enhancing attachment to epithelia in the gut or conferring resistance to bile, ionic detergents and organic acids [28–31]. Based on a three-dimensional model of V. cholerae OmpU, most of the variable regions are located in regions exposed to the outside of the cell (not shown), which supports a host-dependent variation science hypothesis. Conclusions Each year more than half a million people develop cholera. To reduce the burden of this devastating disease, new strategies must be developed. By minimizing the spread of the pathogen, the disease incidence can be reduced. To control a cholera outbreak, quick identification at the start of a potential outbreak and rapid discrimination between epidemic V. cholerae and other V. cholerae isolates could be helpful in introducing effective hygienic measurements [32, 33]. To this point, discrimination between the toxigenic and epidemic V. cholerae strains and the non-pathogenic or less pathogenic strains has required multiple tests. The deviation in amino acid sequences of OmpU homologs of non-epidemic strains from those of the OmpU protein of strain N16961, which is conserved among almost all epidemic strains, makes OmpU an important biomarker to discriminate between epidemic V. cholerae O1/O139 and other V. cholerae isolates.

3 %, 56.5 %, 58.8 %, and 58.5 % in 2007, 2008, 2009, and 2010 in the J-RBR. A recent report from a single center in Japan gave the rates as 77.8 % and 75.9 % between 1979 and 2008 and between 2004 and 2008, respectively [5]. In the present report for the J-RBR, the peak distribution of age was

in the sixties in the combined data for 2009 and 2010. The difference in the rates of primary glomerular disease including IgAN may have been due to the higher mean ages of native biopsy cases in the J-RBR compared to the single center in this period (mean age, 46.7 vs. 40.8 years; age of the peak number, sixties vs. twenties), because the incidence of secondary glomerular disease increases in elderly patients, as reported previously [5]. IgAN is still www.selleckchem.com/products/bay-57-1293.html the most frequently diagnosed disease in native kidney biopsies in Japan (33.0 %, 30.2 %, 31.6 %, and 30.4 % of cases in 2007, 2008, 2009, and 2010 in the BMS-777607 concentration J-RBR) [1, 4–6] similar to other Asian countries [7, 8] and some European countries [9, 10]. The peak distribution of age ranges was the twenties in 2009 and thirties in 2010. In patients with IgAN, the majority (68.1 %) of renal biopsies were performed in CKD stages G1 and G2, with median proteinuria less than 1 g per day (Table 18), suggesting that there was a relatively early diagnosis of this

biopsy-proven disease. In the present clinical data, the degree of proteinuria increased with the progression of the CKD stage, and was more than 1 g per day for the median value in patients with CKD stages G4 and G5 (Tables 18, S1, S2). Previously, the best single predictor for renal deterioration was severe

proteinuria on urine dipstick testing (≥100 mg/dL), followed by hypoalbuminemia, mild hematuria, serum total protein levels, diastolic blood pressure, and histological grade, in a cohort study with 10 years follow-up from 1995 in Japan, the cohort of which exhibited a younger median age (27.7 years) and a peak distribution of age ranges in the teens [11, 12]. A recent report suggested that IgAN with nephrotic syndrome had a worse renal outcome compared to IgAN with non-nephrotic syndrome unless partial or complete remission was achieved [13]. Further studies are necessary click here to elucidate the risk factors or predictors for renal deterioration in IgAN in the present era utilizing the J-RBR, possibly as part of a new secondary clinical study. MN was the most common histopathology in terms of primary glomerular disease other than IgAN in 2007 (31.4 %), 2008 (25.7 %), and 2009 (30.1 %) in the J-RBR and was also the most common type in primary nephrotic syndrome in 2007 (44.0 %) and 2009 (40.3 %) in the J-RBR. MN was also the most common primary cause of nephrotic syndrome in a northern European Caucasian population, with a biopsy rate of 4.5 per million population per year [14]. A total of 68.7 % and 68.8 % of primary MN cases exhibited nephrotic syndrome as the clinical diagnosis at the time of renal biopsy in 2009 and 2010 in the J-RBR. Yokoyama et al.

Arch Microbiol 2004,181(2):122–128.PubMedCrossRef Erlotinib clinical trial 86. Lin WR, Lee CC, Hsu JJ, Hamel JF, Demain AL: Properties of acetate kinase activity in Clostridium thermocellum cell extracts. Appl Biochem Biotechnol 1998,69(2):137–145.PubMedCrossRef 87. Schut GJ, Adams MW: The iron-hydrogenase of Thermotoga maritima utilizes

ferredoxin and NADH synergistically: a new perspective on anaerobic hydrogen production. J Bacteriol 2009,191(13):4451–4457.PubMedCrossRef 88. Shaw AJ, Hogsett DA, Lynd LR: Identification of the [FeFe]-hydrogenase responsible for hydrogen generation in Thermoanaerobacterium saccharolyticum and demonstration of increased ethanol yield via hydrogenase knockout. J Bacteriol 2009,191(20):6457–6464.PubMedCrossRef 89. Payot S, Guedon E, Gelhaye E, Petitdemange H: Induction of lactate production associated with a decrease in NADH cell content enables growth resumption of Clostridium cellulolyticum in batch cultures on cellobiose. Res Microbiol 1999,150(7):465–473.PubMedCrossRef 90. Desvaux M, Guedon E, Petitdemange H: Metabolic flux in cellulose batch and cellulose-fed continuous cultures of Clostridium cellulolyticum in response

to acidic environment. Microbiology 2001,147(Pt 6):1461–1471.PubMed 91. Friedrich Venetoclax nmr B, Buhrke T, Burgdorf T, Lenz O: A hydrogen-sensing multiprotein complex controls aerobic hydrogen metabolism in Ralstonia eutropha. Biochem Soc Trans 2005,33(Pt 1):97–101.PubMed 92. Kleihues L, Lenz O, Bernhard M, Buhrke for T, Friedrich B: The H(2) sensor of Ralstonia eutropha is a member of the subclass of regulatory [NiFe] hydrogenases. J Bacteriol 2000,182(10):2716–2724.PubMedCrossRef 93. Pei J, Zhou Q, Jiang Y, Le Y, Li H, Shao W, Wiegel J: Thermoanaerobacter spp. control ethanol pathway via transcriptional regulation and versatility of key enzymes. Metab Eng

2010,12(5):420–428.PubMedCrossRef 94. Blumenthal M, Johnson MK, Johnson EJ: Distribution of heat labile and heat stable inorganic pyrophosphatase. Can J Microbiol 1967,13(12):1695–1699.PubMedCrossRef 95. Ding YR, Ronimus RS, Morgan HW: Thermotoga maritima phosphofructokinases: expression and characterization of two unique enzymes. J Bacteriol 2001,183(2):791–794.PubMedCrossRef 96. Robinson JR, Sagers RD: Phosphotransacetylase from Clostridium acidiurici. J Bacteriol 1972,112(1):465–473.PubMed 97. Willquist K, Zeidan AA, van Niel EW: Physiological characteristics of the extreme thermophile Caldicellulosiruptor saccharolyticus: an efficient hydrogen cell factory. Microb Cell Fact 2010, 9:89.PubMedCrossRef 98. Heinonen JK, Drake HL: Comparative assessment of inorganic pyrophosphate and pyrophosphatase levels of Escherichia coli, Clostridium pasteurianum, and Clostridium thermoaceticum. FEMS Microbiol Lett 1988, 52:205–208.CrossRef Authors’ contributions TR, JAW, DBL, OVK, and RS conceived and designed the study.

Monocrystalline Si NPs are observed with a lattice space of 0.31 nm corresponding to the Si (111) plane. Their diameter is mainly ranging from 4 to 8 nm with the presence of few smaller and larger NPs. This size distribution has been confirmed on functionalized AZD2014 ic50 Si NPs dispersed in squalane by DLS measurement (Figure 1B). We observe an almost monodisperse size distribution centered at 7 nm with a standard deviation of 2 nm. The efficiency of the functionalization step (Si-C18H37)

has been checked by FTIR analysis of Si NPs before and after reaction. As can be deduced from Figure 2, the surface of initial Si NPs is mainly covered by a native oxide layer giving a large characteristic SiO2 band (Si-O-Si symmetric and asymmetric stretching mode) centered at 1,100 cm−1. Nevertheless, the presence of H at the surface is also clearly evidenced by SiHx waging and rolling modes around 650 cm−1, Oy-SiHx waging around 850 cm−1, SiHx stretching modes at 2,090 cm−1, and Oy-SiHx stretching around 2,230 cm−1. After the functionalization, (i) the SiO2 band is no longer detected selleck compound which confirms the success of the HF washing step to remove the oxide layer, and (ii)

the different Si-H and O-Si-H related bands disappear. At the same time, characteristic bands of ν as (CH3) at 2,962 cm−1, ν as (CH2) at 2,925 cm−1, ν s (CH2) at 2,853 cm−1, and δ (CH2) at 1,467 cm−1 rise. These data prove the efficient replacement of the Si-H and Si-O bonds by the alkyl chains (C18H37). After this essential step that leads to a good dispersion of the Si NPs in nonpolar liquid, their luminescence properties were studied. Figure 1 Transmission electron microscopy image and DLS measurement. (A) TEM image of Si powder initially suspended in ethanol

and deposited on a graphite grid. (B) DLS of functionalized Si NPs dispersed in squalane. Figure 2 FTIR analysis of Si NPs before and after functionalization. very Si-C18H37 means Si NPs functionalized by the C18H37 group (black curve), and Si-H means Si NPs without any chemical modification (red curve). Figure 3 shows temperature-dependent fluorescence spectra of Si NP colloidal suspension in squalane with a concentration C equal to 1 mg/mL. Excitation energy is fixed at the maximum of the excitation spectra (3.94 eV). Figure 3 Temperature-dependent fluorescence spectra of Si NP colloidal suspension in squalane with a concentration of 1 mg/mL. The PL intensity of the Si NPs decreases in the chosen temperature range (from 303 to 383 K). In static conditions, this intensity variation can be used to design a sensitive temperature sensor, but many other parameters can influence the PL intensity in dynamic conditions of a mechanical contact (concentration gradient in the lubricant, pressure variation, nanoparticle flows, etc.).

Cancer 1974, 33:1183–1189.CrossRef 14. Hughes R: Cases illustrative of the influence of belladonna. BMJ 1860, 8:706.CrossRef EPZ015666 cell line 15. Cham C, Chan D, Copplestone J, Prentice A, Lyons C, Jones P, Watkins R: Necrosis of the female breast: a complication of oral anticoagulation in patients with protein S deficiency The Breast. 1994,3(2):116–118.

16. Archer C, Rosenberg W, Scott W, MacDonald D: Progressive bacterial synergistic gangrene in patient with diabetes mellitus. J R Soc Med 1984, 4:77. Supplement Competing interests The authors declare that they have no competing interests. Authors’ contributions designed the study, contributed in literature search, data analysis, manuscript writing. IB, FP, AM and RW helped in study design, data analysis, manuscript writing Pexidartinib concentration and editing. MS, IH, AM SW and WS participated in study design, supervised the write up of the manuscript and edited the manuscript before submission. All the authors read and approved the final manuscript”
“Background Gas gangrene or Clostridial myonecrosis is a necrotic infection of skin and soft tissue and it is characterized by the presence of gas under the skin which is produced by Clostridium. It is a potentially lethal disease which spreads quickly in soft tissues of the body. Tissue necrosis is due to production of exotoxins by spore forming gas producing bacteria

in an environment Dichloromethane dehalogenase of low oxygen. Gas gangrene is subclassified in two categories. Traumatic or postoperative is the most common form accounting for 70% of the cases followed by spontaneous or non traumatic gangrene. C. perfringens is isolated in approximately

80% of patients presenting with traumatic gas gangrene followed by C.septicum, C.novyi, C.histolyticum, C.bifermentans, C.tertium and C.fallax [1–3]. Herein we report a case of gas gangrene which was treated early with surgical debridement and enabled salvage of the limb with significant preservation of its function. Additionally, a review of the literature regarding cases of limb salvage after gas gangrene is presented. Case Presentation A 35-year-old Caucasian man with a history of chronic intravenous drug use presented to the emergency department with right upper limb pain and swelling lasting 24 hours. His initial vital signs were notable for temperature of 39°C, respiratory rate of 25 breaths per minute, heart rate of 120 beat per minute and blood pressure of 141/76 mmHg. He was distressed and on clinical examination severe edema of the upper limb, erythema, blistering of the arm and crepitus over the shoulder and arm was noted [Figure 1a]. At this time, motor and sensory function of the limb was not impaired and pulses of the radial and ulna artery could be palpated. His past medical history consisted of a diagnosis of hepatitis C. Intramuscular injections with normal saline in the shoulder were also reported.

5 Tesla clinical MRI System. Canadian J Neuro Sci 2003, 30:326–332. 26. Moats RA, Velan-Mullan S, Jacobs R, Gonzalez-Gomez I, Dubowitz DJ, Taga T, Khankaldyyan V, Schultz L, Fraser S, Nelson MD, Laug WE: Micro-MRI at 11.7 T of a murine brain tumor model using delayed contrast enhancement. Mol Imaging 2003, 2:150–158.CrossRef

Competing www.selleckchem.com/products/17-AAG(Geldanamycin).html interests The authors declare that they have no competing interests. Authors’ contributions BK carried out the nanoparticle synthesis and modification and drafted the manuscript. JY conceived of the nanoparticle design and condition. MH carried out in vivo MR imaging. JC conceived of the design of the animal experiment. H-OK and EJ participated in the cellular targeting experiment. JHL and S-HR fabricated aptamer sequence. J-SS participated in the modification of magnetic resonance imaging sequence. Y-MH and SH participated in the design of whole study and drafted the manuscript. All authors read and approved the final manuscript.”
“Background

Low-dimensional nanosized effects in CuO systems, especially RG-7388 their different physical properties such as spin-spin [1, 2], electron–phonon [3], spin-phonon interactions [4], and giant negative thermal expansion have recently received a lot of attention [5]. The spin-spin superexchange interaction occurs via the oxygen orbital [4, 6]. The magnetic interactions and Néel transition temperature (T N) of the CuO system are strongly dependent on the exchange interaction and the number of neighboring atoms. A transition from a first-order transition to a commensurate antiferromagnetic state near T N ~ 213 K reported for bulk CuO from neutron scattering experiments [7, 8] is well understood. Controlling the size of CuO nanocrystals resulted in short-range SPTLC1 correlation and commensurate antiferromagnetic (AFM) ordering, where the T N decreased from the bulk value of 213 K [9–11], with decreasing particle size, down to 40 K for 6.6-nm nanoparticles [1, 2] and 13 K for 2- to 3-nm nanorods [12]. It is known that spin-phonon coupling is usually weak and undetectable because symmetric vibrations

of relevant atoms will cancel the contributions from negative and positive displacements. The main feature of cupric oxide is the low-symmetry monoclinic lattice, which differs from the other transition metal monoxides, e.g., MnO, FeO, CoO, and NiO with rock salt structure [13]. The low symmetry of the CuO lattice and the anisotropic dispersion curves indicated lattice vibration which caused a modulation of the spin-phonon interaction. This originated from slight changes in the inter-ionic distances and bond angles, leading to spin-phonon coupling that can be detected in the Raman spectrum, to produce a weak feature at about 230 cm−1 below T N[14, 15]. The discovery of spin-phonon coupling in CuO nanocrystals has led to renewed interest in this phenomenon.

C. Number of apoptotic cells increased after treatment with Beclin 1 siRNA and 100 nM paclitaxel (*: p < 0.05. UOK257: Paclitaxel + random siRNA vs Paclitaxel + beclin 1 siRNA; ACHN 5968: Paclitaxel + random siRNA vs Paclitaxel + beclin 1 siRNA; n = 15). Discussion As a cancer chemotherapeutic drug, paclitaxel has been widely used in chemotherapy for lung cancer, breast cancer, ovarian cancer, and Kaposi’s sarcoma [6]. Kidney cancers are known to be resistant

to conventional chemotherapy [25–27]. Gemcitabine in combination with doxorubicin has only shown some benefit in patients with certain types of kidney cancer [28]. A recent study has shown preferential toxicity of mithramycin and paclitaxel to FLCN-deficient

Selleckchem Adriamycin kidney cancer cell line, UOK257 [10]. If proven, this provides a unique www.selleckchem.com/products/MK-2206.html therapeutic opportunity to a group of tumors related to BHD disease. In this study, we chose paclitaxel for further study its effects on FLCN-deficient kidney cancer cells to find a more effective way to treat these cancer cells. Besides FLCN-deficient cell line UOK257, a cell line derived from a BHD patient’s kidney cancer [29], we also employed a RCC cell line, ACHN, with known FLCN expression and its FLCN expression could be effectively suppressed with siRNA. Although ACHN cell line was not derived from a BHD patient and we would not expect that silencing FCLN with siRNA in ACHN cell line would replicate a RCC cell line derived from a BHD patient, our study did show consistent results between UOK257 DNA Damage inhibitor and ACHN cells in respect to paclitaxel treatment-induced apoptosis and autophagy

in the presence or absence of FLCN. We first demonstrated that paclitaxel could lead to apoptosis as well as autophagy in FLCN-deficient cell lines UOK257 and ACHN-5968. After paclitaxel treatment, a dose-dependent decrease in cell viability and increase in apoptosis were observed in both FLCN-deficient UOK257 and ACHN-5968 cells, while their FLCN-expressing counterparts showed relatively less changes. These results suggested that FLCN-deficient RCC cells were more sensitive to paclitaxel exposure through apoptosis, indicating that FLCN may play a role against paclitaxel-induced apoptosis. We further detected that enhanced autophagy occurred along with apoptosis after paclitaxel treatment in FLCN-deficient RCC cells compared to FLCN-expressing counterparts, suggesting that paclitaxel treatment could also induce autophagy in FLCN-deficient RCC cell lines. Previous studies have suggested that FLCN was involved in apoptosis. While Reiman et al. identified that FLCN might up-regulate the expression of a number of apoptosis genes and activates apoptosis [14]. Baba et al. found that FLCN interacted with the Bcl 2 family to inhibit apoptosis in B cells in FLCN knockout mouse [16].