Hepatocellular carcinoma in hepatitis-negative patients with thalassemia intermedia: a closer look at the role of siderosis

Abstract Patients with thalassemia are often exposed to several risk factors for developing hepatocellular carcinoma (HCC) due to their repeated transfusions. However, even transfusion-independent patients with thalassemia intermedia (TI) can develop HCC, which is mainly attributed to a state of iron overload. We report here two cases and review the literature for the association between TI and HCC. Along with our cases, a total of 36 cases of HCC in thalassemic patients were reported in the literature. Of these, 22 (61%) were TI patients with 6 (27%) of them being hepatitis B and C negative. There was no consistency in their characteristics; therefore, we recommended screening thresholds for HCC in TI patients based on their total liver iron concentration (LIC)

The role of carbon and nitrogen sources in the production of bioactive compounds in Monascus fermentation products: a mini review

Angkak is one of the Monascus fermented products with rice as a substrate. In addition, Chinese yam, potatoes, soybean, ginseng and onions can be used as a substrate for fermentation products by Monascus sp. It was known that the fermented product by Monascus sp. produces several bioactive compounds that have antihyperlipidemic activity. These bioactive compounds are monacolin-K and pigment compounds (monascin and ankaflavin). Each of these compounds has different cholesterol inhibitory activity. The production of these bioactive compounds is strongly influenced by the nutritional composition of the fermentation media. The addition of the right carbon and nitrogen sources can accelerate the production of bioactive compounds by Monascus sp

The role of carbon and nitrogen sources in the production of bioactive compounds in Monascus fermentation products: a mini review

Angkak is one of the Monascus fermented products with rice as a substrate. In addition, Chinese yam, potatoes, soybean, ginseng and onions can be used as a substrate for fermentation products by Monascus sp. It was known that the fermented product by Monascus sp. produces several bioactive compounds that have antihyperlipidemic activity. These bioactive compounds are monacolin-K and pigment compounds (monascin and ankaflavin). Each of these compounds has different cholesterol inhibitory activity. The production of these bioactive compounds is strongly influenced by the nutritional composition of the fermentation media. The addition of the right carbon and nitrogen sources can accelerate the production of bioactive compounds by Monascus sp

Aryloxy diester phosphonamidate prodrugs of phosphoantigens (ProPAgens) as potent activators of Vγ9/Vδ2 T-cell immune responses

Vγ9/Vδ2 T-cells are activated by pyrophosphate-containing small molecules known as phosphoantigens (PAgs). The presence of the pyrophosphate group in these PAgs has limited their drug-like properties because of its instability and polar nature. In this work, we report a novel and short Grubbs olefin metathesis-mediated synthesis of methylene and difluoromethylene monophosphonate derivatives of the PAg (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBP) as well as their aryloxy diester phosphonamidate prodrugs, termed ProPAgens. These prodrugs showed excellent stability in human serum (t1/2 > 12 h) and potent activation of Vγ9/Vδ2 T-cells (EC50 ranging from 5 fM to 73 nM), which translated into sub-nanomolar γδ T-cell-mediated eradication of bladder cancer cells in vitro. Additionally, a combination of in silico and in vitro enzymatic assays demonstrated the metabolism of these phosphonamidates to release the unmasked PAg monophosphonate species. Collectively, this work establishes HMBP monophosphonate ProPAgens as ideal candidates for further investigation as novel cancer immunotherapeutic agents

Efficient framework for brain tumor detection using different deep learning techniques

The brain tumor is an urgent malignancy caused by unregulated cell division. Tumors are classified using a biopsy, which is normally performed after the final brain surgery. Deep learning technology advancements have assisted the health professionals in medical imaging for the medical diagnosis of several symptoms. In this paper, transfer-learning-based models in addition to a Convolutional Neural Network (CNN) called BRAIN-TUMOR-net trained from scratch are introduced to classify brain magnetic resonance images into tumor or normal cases. A comparison between the pre-trained InceptionResNetv2, Inceptionv3, and ResNet50 models and the proposed BRAIN-TUMOR-net is introduced. The performance of the proposed model is tested on three publicly available Magnetic Resonance Imaging (MRI) datasets. The simulation results show that the BRAIN-TUMOR-net achieves the highest accuracy compared to other models. It achieves 100%, 97%, and 84.78% accuracy levels for three different MRI datasets. In addition, the k-fold cross-validation technique is used to allow robust classification. Moreover, three different unsupervised clustering techniques are utilized for segmentation

Synthesis and biological evaluation of (E)-4-hydroxy-3-methylbut2-enyl phosphate (HMBP) aryloxy triester phosphoramidate Prdrugs as activators of Vγ9/Vδ2 T-cells immune response

The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This work highlights the promise of this prodrug technology in the discovery of novel immunotherapeutics

In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration

Purpose: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 +/- 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes

Differential cartilaginous tissue formation by human synovial membrane, fat pad, meniscus cells and articular chondrocytes

Objective: To identify an appropriate cell source for the generation of meniscus substitutes, among those which would be available by arthroscopy of injured knee joints. Methods: Human inner meniscus cells, fat pad cells (FPC), synovial membrane cells (SMC) and articular chondrocytes (AC) were expanded with or without specific growth factors (Transforming growth factor-betal, Fibroblast growth factor-2 and Plate let-derived growth factor bb, TFP) and then induced to form three-dimensional cartilaginous tissues in pellet cultures, or using a hyaluronan-based scaffold (Hyaff(R)-11), in culture or in nude mice. Human native menisci were assessed as reference. Results: Cell expansion with TFP enhanced glycosaminoglycan (GAG) deposition by all cell types (up to 4.1-fold) and messenger RNA expression of collagen type II by FPC and SMC (up to 472-fold) following pellet culture. In all models, tissues generated by AC contained the highest fractions of GAG (up to 1.9 were positively stained for collagen type II (specific of the inner avascular region of meniscus), type IV (mainly present in the outer vascularized region of meniscus) and types I, III and VI (common to both meniscus regions). Instead, inner meniscus, FPC and SMC developed tissues containing negligible GAG and no detectable collagen type II protein. Tissues generated by AC remained biochemically and phenotypically stable upon ectopic implantation. Conclusions: Under our experimental conditions, only AC generated tissues containing relevant amounts of GAG and with cell phenotypes compatible with those of the inner and outer meniscus regions. Instead, the other investigated cell sources formed tissues resembling only the outer region of meniscus. It remains to be determined whether grafts based on AC will have the ability to reach the complex structural and functional organization typical of meniscus tissue. (C) 2006 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights rese