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Background and Aims: Fascia iliaca compartment block (FICB) is increasingly being used for anaesthesia and analgesia of the hip, knee and thigh. It can be administered via two ultrasound-guided approaches, suprainguinal and infrainguinal. This study aimed to compare the analgesic efficacy of the suprainguinal approach of FICB with infrainguinal approach of FICB in patients undergoing above knee orthopaedic surgeries. Methods: In this single-centre, double-blinded randomised trial, 32 patients undergoing above knee lower limb orthopaedic surgery under spinal anaesthesia were randomised into group I (infrainguinal FICB) and S (suprainguinal FICB). They were given ultrasound-guided FICB with 30 mL 0.2% ropivacaine for postoperative analgesia using the respective approaches. Injection tramadol was administered as a rescue analgesic when Numeric Rating Scale (NRS) ≥4. A blinded observer recorded pain score (NRS) from the initiation of the block every 2 h for 24 h. Time to first rescue analgesia, total duration of analgesia and analgesic consumption, and patient satisfaction score were noted. Results: The mean pain scores were comparable between the two groups at all time intervals till 24 h except at 12 h and 20 h, when pain intensity was significantly less in group S than in group I. Total tramadol consumption was also significantly less in group S. There was no significant difference in time to first rescue analgesia and total duration of analgesia between the two groups. At 24 h, the patient satisfaction score was significantly better in group S. Conclusion: Suprainguinal FICB has superior analgesic efficacy over infrainguinal FICB in terms of reduced pain intensity, reduced 24-h tramadol consumption and better patient satisfaction. [ABSTRACT FROM AUTHOR]

• 25 mm melt-spun ribbon of different thickness prepared using commercial raw materials. • Ribbon thickness influences amorphous matrix structure & nanocrystallization process. • Hysteresis contribution dominates sub-kHz Core-loss properties. • Low Core Loss P ≤ 0.4 W/kg @50 Hz/1.6 T is achieved. The present work investigates the structure, soft-magnetic and core-loss properties of 25 mm wide Fe 83 Si 2 B 9 P 4 Nb 1 Cu 1 nanocrystalline ribbons. The melt-spun precursor ribbons of the thickness of 22 and 28 µm were prepared using commercial raw materials under ambient atmosphere. The XRD and DSC results show predominantly amorphous and hetero-amorphous structure for 22 and 28 µm ribbons in the as-quenched state. Further, the partial crystallization annealing leads to thickness dependent nanocrystallization process, wherein the thinner 22 µm ribbon shows sluggish primary(α-Fe(Si)) and delayed secondary(Fe 3 (B 0.8 P 0.2)) crystallization process compared to 28 µm ribbons. The difference is explained through as-quenched precursor matrix structure and selective solute re-distribution of the intergranular region during nanocrystallization. Moreover, the higher crystallite size (D) and volume fraction(V cr) of α-Fe(Si) nanocrystallites are observed for the 28 µm ribbon in the optimal annealing window. Under optimal annealing conditions, the 28 µm nanocrystalline ribbon (733 K) shows better AC soft-magnetic properties including B 800 of 1.62 T, H c of 15.7 A/m, B r /B s ratio ≥ 0.8 compared to B 800 of 1.59 T, H c of 17 A/m and B r /B s ratio ≥ 0.7 of 22 µm (743 K) ribbon. The 28 µm ribbon shows a low core loss (P) of 0.34 W/kg under 50 Hz, 1.5 T compared to P > 0.65 W/kg for 22 µm ribbons. The lower core-loss behaviour of thicker 28 µm in the sub-kHz frequency regime has been explained based on the nanocrystalline microstructure and loss coefficients (hysteresis and eddy current). The work compares the AC core-loss properties with reported Fe-rich nanocrystalline alloys and also discusses the scope of improving B 800 beyond 1.65 T for the present alloys. [ABSTRACT FROM AUTHOR]

PURPOSE: To develop a novel artificial intelligence (AI)–powered method for the prediction of prostate cancer (PCa) early recurrence and identification of driver regions in PCa of all Gleason Grade Group (GGG). MATERIALS AND METHODS: Deep convolutional neural networks were used to develop the AI model. The AI model was trained on The Cancer Genome Atlas Prostatic Adenocarcinoma (TCGA-PRAD) whole slide images (WSI) and data set (n = 243) to predict 3-year biochemical recurrence after radical prostatectomy (RP) and was subsequently validated on WSI from patients with PCa (n = 173) from the University of Wisconsin-Madison. RESULTS: Our AI-powered platform can extract visual and subvisual morphologic features from WSI to identify driver regions predictive of early recurrence of PCa (regions of interest [ROIs]) after RP. The ROIs were ranked with AI-morphometric scores, which were prognostic for 3-year biochemical recurrence (area under the curve [AUC], 0.78), which is significantly better than the GGG overall (AUC, 0.62). The AI-morphometric scores also showed high accuracy in the prediction of recurrence for low- or intermediate-risk PCa—AUC, 0.76, 0.84, and 0.81 for GGG1, GGG2, and GGG3, respectively. These patients could benefit the most from timely adjuvant therapy after RP. The predictive value of the high-scored ROIs was validated by known PCa biomarkers studied. With this focused biomarker analysis, a potentially new STING pathway–related PCa biomarker—TMEM173—was identified. CONCLUSION: Our study introduces a novel approach for identifying patients with PCa at risk for early recurrence regardless of their GGG status and for identifying cancer drivers for focused evolution-aware novel biomarker discovery. AI-powered platform can extract morphologic features from digital slide images to predict prostate cancer outcomes. [ABSTRACT FROM AUTHOR]

Glass forming ability (GFA) and soft-magnetic behaviour of melt-spun Fe 69 C 5.5 P 11.5 Mn 0.4 Si 2.3 Cr 1.8 Mo 1 B 8.5 (alloy 2) and Fe 68 C 9 P 12 Mn 1 Si 3 Nb 2 B 5 , (alloy 3) alloys prepared using high phosphorous pig iron (h-PI, Fe 80 C 14 P 2.2 Mn 0.4 Si 3.4) has been studied. The glass formation, thermo-physical and soft-magnetic properties of the alloys were analyzed for different quenching rates by varying wheel speed as 23, 26, 33, 39 and 43 m/s. The simultaneous incorporation of alloying elements (Cr, Mo, Nb) and metalloids (C, B, P, Si) transforms h-PI to complete glassy alloy, even at low quenching rates. The melt quenching rate influences the thermal parameters and Curie temperature of glassy ribbons in an opposite way. Amongst all, FeCPMnSiCrMoB glassy alloy show superior combination of higher glass transition temperature of 788 K, super cooled region of 34 K, glass Curie temperature of 552 K, coercivity less than 13 A/m and maximum saturation magnetization of 1.1 T. In addition, the annealing treatment at 758 K improves magnetic softness (1.7 A/m) of the alloy by relaxation of quenched-in stresses. The comparison of developed glassy alloy with similar Fe-glassy alloys and SENNTIX type alloys show best combination of thermo-physical and magnetic properties. The glassy alloy prepared using blast furnace high phosphorous pig iron can be used for uniformly gapped soft-magnetic cores. • Fe-based glassy alloys developed using novel high Phosphorous Pig iron. • Thermo-physical parameters exhibit quenching rate dependency. • Stress-relieved glassy alloy 2 show T g of 782 K, H c of 1.7 A/m and M s of 1.05 T. • A Potential candidate for medium-frequency electromagnetic powder cores. [ABSTRACT FROM AUTHOR]

The electromagnetic interference shielding effectiveness (EMI SE) of amorphous and annealed melt-spun ribbons having typical composition of Co 72.5 Si 12.5 B 15 , (Fe 0.65 Co 0.35) 83 Si 1.3 B 11.7 Nb 3 Cu 1 , Fe 80 Si 8 B 12 and Fe 83 Si 2 B 13 Nb 2 were studied in the 0.2–8.5 GHz microwave range. The amorphous nature of the as-quenched ribbons was confirmed by X-ray diffraction patterns and differential scanning calorimetry (DSC). The flexible electromagnetic wave absorber ribbons of CoSiB, FeSiB, and FeCoSiBNbCu based alloys exhibit ∼99.99% attenuation of electromagnetic waves in the entire 0.2–8.5 GHz (L, S and C-band) range. Both as-quenched and annealed amorphous ribbons of Co 72.5 Si 12.5 B 15 and Fe 80 Si 8 B 12 are electromagnetically active and total electromagnetic shielding effectiveness (SE T) of ribbons found to be ∼36 dB, ∼34 dB throughout the test range. The EMI shielding properties deteriorates for FeCoSiBNbCu and FeSiBNb based nanocomposite ribbons achieved by in-situ crystallization annealing. The electromagnetic shielding of magnetic ribbons is effected mainly by absorption mechanism due to high electrical resistivity and magnetic permeability. The CoSiB and FeSiB melt-spun ribbons can be a potential magnetic filler for military and stealth applications in L, S and C-band range. [ABSTRACT FROM AUTHOR]

The effect of minor Al addition on structural, crystallization, soft magnetic behaviour and magnetic field induced anisotropy through DC Joule annealing in (Fe 53 . 95 Co 29.05 ) 83 Si 1.3 B 11.7-x Nb 3 Cu 1 Al x , (X = 0, 1) alloys has been studied. The Al added as-quenched melt spun ribbons show good glass forming ability, better thermo-physical properties like a high T x1 of 438 °C, Tc am of 435 °C and Tc nc of 906 °C, compared to T x1 of 389 °C, Tc am of 409 °C and Tc nc of 900 °C for the alloy without Al addition. The longitudinal magnetic field annealed Al added alloy exhibits low Hc of 12.92 A/m and maximum Ms. of 1.78 T. The better soft magnetic properties of Al added alloy are achieved through a high nucleation density of BCC-FeCo(Al) nanocrystallites having low K 1 and λ values. The as-quenched alloys possess high magneto-strain exceeding 30 ppm and approach near zero value on nanocrystallization. The longitudinal magnetic field assisted DC Joule annealing, having current density (J) in the range of J = 20–25 A/mm 2 promotes good magnetic softening due to precipitation of 5–35 nm nanocrystallites as explained by extended-random anisotropy model. The Al added alloy shows better magnetic field induced anisotropy (K u ) on nanocrystallization and shows visible change in the shape of hysteresis loop. [ABSTRACT FROM AUTHOR]

The compositional effect of magneto-elastic and magnetostriction properties of Fe-rich Fe 81 B 15−x P x Si 2 Nb 1 Cu 1 (ii) Fe 82 B 14−x P x Si 2 Nb 1 Cu 1 and (iii) Fe 83 B 13−x P x Si 2 Nb 1 Cu 1 (x = 0, 4, 8) amorphous and annealed nanocrystalline alloy ribbons were investigated. The present study adds knowledge to the limited magnetostriction literature available for Fe-rich nanocrystalline alloys by systematically varying the Fe and P content. A combination of Becker-Kersten and small angle magnetization rotation (SAMR) techniques has been employed for the magnetostriction (λs) evaluation. Both the as-quenched and nanocrystalline ribbons exhibit large positive magnetostriction and show strong compositional dependence to the P content. In the as-quenched condition, 4 at% P addition shows maximum magneto-elastic response and magnetostriction constant, with Fe 81 B 11 P 4 Si 2 Nb 1 Cu 1 alloy exhibiting a maximum of + 52 ppm and P-free Fe 83 B 13 Si 2 Nb 1 Cu 1 alloy exhibiting a minimum of + 27 ppm. In the nanocrystalline state, a slight reduction of magnetostriction is seen for all alloys, with a maximum of + 32 ppm (4 at% P) and a minimum of + 22 ppm (P-free) in Fe83 at% alloys. The unusual large magnetostriction of optimally annealed samples is attributed to the relatively low crystal volume fraction (30–45%) of nanocrystalline ribbons. The lowest magnetostriction of Fe 83 B 13 Si 2 Nb 1 Cu 1 alloy in both as-quenched and annealed state is explained based on ribbon structural heterogeneity consisting of crystal nuclei and textured α-Fe surface crystallization. The study reveals a contradictory response of magneto-crystal anisotropy (grain size reduction) and magneto-elastic anisotropy to the P addition and ribbon structural heterogeneity. The study discusses the implications of the large magneto-elastic anisotropy associated with Fe-rich nanocrystalline ribbons and the way forward for improving their magnetic softness. [Display omitted] • Compositional effects of Fe and P addition on magnetostriction of Fe-rich nanocrystalline alloys. • The P addition (∼ 4–8 at%) increases the magnetostriction constant in Fe-rich alloys (81–83 at%). • The ribbons with surface and matrix structural heterogeneity exhibit low magnetostriction. • Large magnetostriction of nanocrystalline alloys due to low crystal volume fraction. • P content and structural heterogeneity show opposing effects towards magneto-crystal and magneto-elastic anisotropy. [ABSTRACT FROM AUTHOR]

The investigation addresses the role of Al in devitrification stage of a series of (Co 94 Fe 6) 72.5 Si 12.5−x Al x B 13 Cr 2 (X = 0, 2, 4, 6 at%) rapidly quenched microwires. The incorporation of Al displayed reduction in primary onset and activation energy (A.E) while it facilitated widening of span between primary and secondary crystallization onsets. The Giant Magneto-Impedance (GMI) behaviour was influenced by Al concentration as well as applied uniaxial stress. Optimal Al containing alloy (x ∼ 2 at%) displayed signature of asymmetric dual peak at the operating frequency of 1 MHz and its prospective application as a very low magnetic field sensor in pre-stressed condition. However, with increasing stress, the asymmetric character transformed to symmetric dual peak which is attributed to the transition of transverse anisotropy to circular anisotropy via helical anisotropy. High stress sensitivity has been attributed to either dominant transverse or circular anisotropy. The transition of stress induced anisotropies in the microwires has been portrayed schematically to elucidate the transitions. • The Al incorporation for Si impacts on magnetostriction and anisotropy of microwires. • The microwires reveal change in GMI peak shape with applied stress. • The change in shape of GMI peak (dual, single) with uniaxial stress is associated to change in anisotropy. • Transition in helical, circumferential and transverse anisotropy with stress and compositional is discussed. [ABSTRACT FROM AUTHOR]

• Compositional dependence of structural heterogeneity in Fe-rich melt-spun alloys. • Rapid coarsening of pre-existing crystal nuclei at low annealing temperatures. • Complex crystallization and magnetic property correlation of hetero-amorphous alloy. • Cu alters growth morphology of pre-existing crystal and delays boride formation. The sequential, multi-stage crystallization and magnetic hardening behaviour of Fe 82 B 14 Si 2 Nb 2, Fe 83 B 13 Si 2 Nb 2, Fe 83 B 12 Si 2 Nb 2 Cu 1 and Fe 85 B 13 Nb 2 melt-spun alloys have been investigated. The microstructure-crystallization-magnetic property relationship was established using X-ray diffractometry (XRD), differential scanning calorimetry (DSC), magnetometry, transmission electron microscopy (TEM) and magneto-optical Kerr effect microscopy (MOKE) techniques. The increase of Fe content (>82 at%) of as-quenched ribbons imparts microstructural heterogeneity across the ribbon cross–section; i.e., textured α-Fe crystals at the free surface to hetero-amorphous microstructure in the bulk matrix. The isochronal annealing of hetero-amorphous alloys depicts simultaneous surface and bulk crystallization process occurring before and after the crystallization onset temperature (T x1) temperature. The annealing temperature range (T a < T x1) coinciding with the paramagnetic region of the thermo-magnetic plot, induces irreversible magnetic hardening due to simultaneous coarsening of pre-existing crystal nuclei and exchange de-coupling between nanocrystal and intergranular matrix. The onset of primary crystallization in the pre-crystallized ribbons results in bimodal nanocrystallite distribution having an average crystallite size exceeding the ferromagnetic exchange length of Fe-based alloys. The minor Cu addition alters the growth morphology of pre-existing nuclei from dendrite-like to equiaxed, assisting heterogeneous nucleation and improving intergranular amorphous stability by delaying boride precipitation. The soft-magnetic property deterioration of partially crystallized ribbons is discussed within the framework of Extended-Random Anisotropy models. [ABSTRACT FROM AUTHOR]

The effect of varying thickness on structure and thermal properties is investigated in Fe–B–Nb and Fe–B–Si–Nb glassy alloy systems with the addition of different Nb and Co content, respectively. Accordingly, four alloys with the nominal compositions of Fe 76-x B 18 Nb 6+x (x = 0, 2) and (Fe 1-y Co y) 72 B 12 Si 12 Nb 4 (y = 0, 0.5) are processed in the forms of ribbon and rod. All alloys of ribbons represent amorphous structure, while those of rods explain the crystalline structure with the exception of heteromorphous structure for Co added alloy. The Nb addition causes about same glass transition temperature (Tg) but increases crystallization onset (Tx), resulting in a wider supercooled liquid region (ΔTx = Tx-Tg). Moreover, Nb also improves glass forming ability (GFA) with more free volume generation and higher structural relaxation exothermic heat (ΔH 0). The Co addition also improves free volume generation and higher ΔH 0 for ribbon, but lower amount free volume generation in bulk alloys (rod) than ribbon. • Both composition and processing routes affect structure and thermal behaviours in Fe-B-Nb and Fe-B-Si-Nb alloy systems. • Nb and Co addition improve glass forming ability with more free volume generation. • Free volume generation in rod is lower than ribbon for a Co added alloy. [ABSTRACT FROM AUTHOR]

• P addition restricts formation of hetero-amorphous structure in Fe-rich alloys. • P addition stabilize intergranular amorphous matrix during de-vitrification. • The ribbon heterogeneity induced mixed anisotropy governs the coercivity (H c). • 4 at% P content show optimal magnetic properties of low H c and High Ms. The influence of P on amorphizing ability, as-quenched microstructure, thermo-physical and soft magnetic properties of Fe–rich (i) Fe 81 B 15-x P x Si 2 Nb 1 Cu 1 (ii) Fe 82 B 14-x P x Si 2 Nb 1 Cu 1 and (iii) Fe 83 B 13-x P x Si 2 Nb 1 Cu 1 (x = 0, 2, 4, 6, 8 at%) melt-spun alloys are investigated. The substitution of P improves amorphization of alloys and restricts the formation of hetero-amorphous microstructure for Fe 83 at% ribbons at around (x = 8). The improvement in short range ordering of P containing clusters with varying Fe content has been discussed within the framework of Cluster-Glue atom model and supported by experimental thermal parameters. The optimal P content in Fe-rich alloys in the range of 4 ≤ x ≤ 6 delivered favourable thermal properties of high primary and secondary crystallization onset temperature viz; T x1 , T x2 and temperature span ΔT between these onsets. The P substitution drastically restricts the precipitation of secondary crystallites with reduced enthalpy of secondary crystallisation (ΔH 2) during annealing and favourably assists in attaining maximum magnetic moment during the primary crystallization stage. Moreover, the P substitution (4–8 at%) effects refinement of α-Fe nanocrystallites and promotes low coercivity (H c < 20 A/m) in nanocomposite alloys. On contrary, the P substitution linearly reduces saturation magnetization (M s) by weakening ferromagnetic exchange coupling and ferromagnetic dilution. An optimal content of 4 at% P offers favourable combination of low H c and High M s in both amorphous and nanocomposite state. [ABSTRACT FROM AUTHOR]

Mesothelioma is an aggressive cancer of the mesothelial layer associated with an extensive fibrotic response. The latter is in large part mediated by cancer-associated fibroblasts which mediate tumour progression and poor prognosis. However, understanding of the crosstalk between cancer cells and fibroblasts in this disease is mostly lacking. Here, using co-cultures of patient-derived mesothelioma cell lines and lung fibroblasts, we demonstrate that fibroblast activation is a self-propagated process producing a fibrotic extracellular matrix (ECM) and triggering drug resistance in mesothelioma cells. Following characterisation of mesothelioma cells/fibroblasts signalling crosstalk, we identify several FDA-approved targeted therapies as far more potent than standard-of-care Cisplatin/Pemetrexed in ECM-embedded co-culture spheroid models. In particular, the SRC family kinase inhibitor, Saracatinib, extends overall survival well beyond standard-of-care in a mesothelioma genetically-engineered mouse model. In short, we lay the foundation for the rational design of novel therapeutic strategies targeting mesothelioma/fibroblast communication for the treatment of mesothelioma patients., (© 2023. The Author(s).)

Tumours expressing human chorionic gonadotropin (hCG), the majority of which are difficult to biopsy due to their vascularity, have disparate prognoses depending on their origin. As optimal management relies on accurate diagnosis, we aimed to develop a sensitive cell free DNA (cfDNA) assay to non-invasively distinguish between cases of gestational and non-gestational origin. Deep error-corrected Illumina sequencing of 195 common single nucleotide polymorphisms (SNPs) in cfDNA and matched genomic DNA from 36 patients with hCG-secreting tumours (serum hCG 5 to 3,042,881 IU/L) and 7 controls with normal hCG levels (≤4 IU/L) was performed. cfDNA from confirmed gestational tumours with hCG levels ranging from 1497 to 700,855 IU/L had multiple (n ≥ 12) 'non-host' alleles (i.e. alleles of paternal origin). In such cases the non-host fraction of cfDNA ranged from 0.3 to 40.4% and correlated with serum hCG levels. At lower hCG levels the ability to detect non-host cfDNA was variable, with the detection limit dependent on the type of causative pregnancy. Patients with non-gestational tumours were identifiable by the absence of non-host cfDNA, with copy number alterations detectable in the majority of cases. Following validation in a larger cohort, our sensitive assay will enable clinicians to better inform patients, for whom biopsy is inappropriate, of their prognosis and provide optimum management., (© 2022. The Author(s).)

Low-risk gestational trophoblastic neoplasia including choriocarcinoma is often effectively treated with Methotrexate (MTX) as a first line therapy. However, MTX resistance (MTX-R) occurs in at least ≈33% of cases. This can sometimes be salvaged with actinomycin-D but often requires more toxic combination chemotherapy. Moreover, additional therapy may be needed and, for high-risk patients, 5% still die from the multidrug-resistant disease. Consequently, new treatments that are less toxic and could reverse MTX-R are needed. Here, we compared the proteome/phosphoproteome of MTX-resistant and sensitive choriocarcinoma cells using quantitative mass-spectrometry to identify therapeutically actionable molecular changes associated with MTX-R. Bioinformatics analysis of the proteomic data identified cell cycle and DNA damage repair as major pathways associated with MTX-R. MTX-R choriocarcinoma cells undergo cell cycle delay in G1 phase that enables them to repair DNA damage more efficiently through non-homologous end joining in an ATR-dependent manner. Increased expression of cyclin-dependent kinase 4 (CDK4) and loss of p16 Ink4a in resistant cells suggested that CDK4 inhibition may be a strategy to treat MTX-R choriocarcinoma. Indeed, inhibition of CDK4/6 using genetic silencing or the clinically relevant inhibitor, Palbociclib, induced growth inhibition both in vitro and in an orthotopic in vivo mouse model. Finally, targeting the ATR pathway, genetically or pharmacologically, re-sensitised resistant cells to MTX in vitro and potently prevented the growth of MTX-R tumours in vivo. In short, we identified two novel therapeutic strategies to tackle MTX-R choriocarcinoma that could rapidly be translated into the clinic., (© 2022. The Author(s).)

The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and the terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino propionic acid (Dpr) with fewer methylene groups in the side chain remains an important question! The propensity of aminoacyl-tRNA (aa-tRNA) model substrates towards self-degradation via intramolecular lactamization was studied using UV spectroscopy and 1 H-NMR titration, which showed that Lys and Arg remain stable, and Orn and Dab cyclize to lactam. Hydrophobicity-assisted surface mediated model peptide formation highlighted that the microenvironment and p K a perturbation led to poor regioselectivity (α-amine vs. terminal amine) in Dpr and other non-proteinogenic analogues. The α-selectivity became even poorer in the presence of phosphate, making them ill-suited for peptide synthesis. Superior regioselectivity of the Lys aa-tRNA model substrate suggests that the extra methylene bridge helped nature to separate the microenvironments of the α-amine and ε-amine to synthesize the peptide backbone.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes such as processing of heterogeneous nuclear RNAs (hnRNAs) into mature mRNAs, RNA splicing, transactivation of gene expression, and modulation of protein translation. hnRNPA1 is the most abundant and ubiquitously expressed member of this protein family and has been shown to be involved in multiple molecular events driving malignant transformation. In addition to selective mRNA splicing events promoting expression of specific protein variants, hnRNPA1 regulates the gene expression and translation of several key players associated with tumorigenesis and cancer progression. Here, we will summarize our current knowledge of the involvement of hnRNPA1 in cancer, including its roles in regulating cell proliferation, invasiveness, metabolism, adaptation to stress and immortalization. WIREs RNA 2017, 8:e1431. doi: 10.1002/wrna.1431 For further resources related to this article, please visit the WIREs website., (© 2017 Wiley Periodicals, Inc.)

The objective of the present study was to evaluate the effect of beta-sitosterol, a plant sterol that induces apoptosis in breast cancer cells, on two pathways leading to apoptosis. These pathways are classified based on the localization of the initiated signal, extrinsic and intrinsic pathways. Extrinsic and intrinsic pathways are catalyzed by caspases 8 and 9, respectively, which leads to the activation of the executioner caspase 3. The results of the present study indicate that beta-sitosterol supplementation at 16 microM for 3 days to MDA-MB-231 cells induces 39% and 80% increases in the activities of caspases 8 and 9, respectively, compared to cholesterol supplemented cells or controls. There was also a 3-fold increase in the activity of caspase 3. Sterol treatment had no effect on the quantities of the enzymes. It is concluded that beta-sitosterol may induce apoptosis through the two pathways but was more pronounced on the intrinsic pathway.