Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent.

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

Repurposing of investigational cancer drugs: Early phase discovery of dengue virus NS2B/NS3 protease inhibitors.

Dengue fever is a neglected vector-borne disease and is more prevalent in Asia. Currently, no specific treatment is available. Given the time and cost of de novo drug discovery and development, an alternative option of drug repurposing is becoming an effective tool. We screened a library of 1127 pharmacologically active, metabolically stable, and structurally diverse small anticancer molecules to identify inhibitors of the dengue virus (DENV) NS2B/NS3 protease. Enzyme kinetics and inhibition data revealed four B-cell lymphoma 2 inhibitors, that is, ABT263, ABT737, AT101, and TW37, as potent inhibitors of DENV NS2B/NS3 protease, with IC50 values of 0.86, 1.15, 0.81, and 0.89 µM, respectively. Mode of inhibition experiments and computational docking analyses indicated that ABT263 and ABT737 are competitive inhibitors, whereas AT101 and TW37 are noncompetitive inhibitors of the protease. With further evaluation, the identified inhibitors of the DENV NS2B/NS3 protease have the potential to be developed into specific anti-dengue therapeutics.

Identification and Characterization of Natural and Semisynthetic Quinones as Aurora Kinase Inhibitors.

Aurora kinases (Aurora A, B, and C) are a family of serine/threonine kinases that play critical roles during mitotic initiation and progression. Aurora A and B kinases are ubiquitously expressed, and their overexpression and/or amplification in many cancers have been associated with poor prognosis. Several inhibitors that target Aurora kinases A, B, or both have been developed during the past decade with efficacy in different in vitro and in vivo models for a variety of cancers. Recent studies have also identified Aurora A as a synthetic lethal target for different tumor suppressors, including RB1, SMARCA4, and ARID1A, which signifies the need for Aurora-A-selective inhibitors. Here, we report the screening of a small library of quinones (nine naphthoquinones, one orthoquinone, and one anthraquinone) in a biochemical assay for Aurora A kinase that resulted in the identification of several quinones as inhibitors. IC50 determination against Aurora A and B kinases revealed the inhibition of both kinases with selectivity toward Aurora A. Two of the compounds, natural quinone naphthazarin (1) and a pseudo anthraquinone, 2-(chloromethyl)quinizarin (11), potently inhibited the proliferation of various cancer cell lines with IC50 values ranging from 0.16 ± 0.15 to 1.7 ± 0.06 and 0.15 ± 0.04 to 6.3 ± 1.8 µM, respectively. Treatment of cancer cells with these compounds for 24 h resulted in abrogated mitosis and apoptotic cell death. Direct binding of both the compounds with Aurora A kinase was also confirmed through STD NMR analysis. Docking studies predicted the binding of both compounds to the ATP binding pocket of Aurora A kinase. We have, therefore, identified quinones as Aurora kinase inhibitors that can serve as a lead for future drug discovery endeavors.

The Impact of Telemonitoring on Improving Glycemic and Metabolic Control in Previously Lost-to-Follow-Up Patients with Type 2 Diabetes Mellitus: A Single-Center Interventional Study in the United Arab Emirates.

Background: Telemonitoring (TM), mobile-phone technology for health, and bluetooth-enabled self-monitoring devices represent innovative solutions for proper glycemic control, compliance and monitoring, and access to providers. Objective: In this study, we evaluated the impact of TM devices on glycemic control and the compliance of 38 previously lost-to-follow-up (LTFU) patients with type 2 diabetes mellitus (T2DM). Methods: This was an interventional single-center study that randomly recruited LTFU patients from the Dubai Diabetes Center (DDC), UAE. After contact and recruitment by phone, patients had an initial visit at which they were provided with home-based TM devices. A follow-up visit was conducted three months later. Results: The mean HbA1c decreased significantly from 10.3 ± 1.9% at baseline to 7.4 ± 1.5% at the end of follow-up, with a mean difference (MD) of -2.9% [95% CI: -3.6 to -2.2]. The percentage of patients with HbA1c <7% was 50% after three months. Home-based blood sugar monitor devices showed a significant reduction in fasting blood glucose (FBG) after three months (MD = -40.1 mg/dL, 95% CI: -70.8 to -9.3). A significant reduction was observed in terms of body weight after three months (MD = -1.3 kg, 95% CI: -2.5 to -0.08). The mean number of days the participants used a device was the highest for portable pill dispensers (86.5 ± 22.8 days), followed by a OneTouch® blood glucose monitor (72.9 ± 23.5 days). Conclusions: TM led to significant improvements in overall diabetes outcomes, including glycemic control and body weight, indicating its effectiveness in a challenging population of T2DM patients who had previously been lost to follow-up.

CCT245718, a dual FLT3/Aurora A inhibitor overcomes D835Y-mediated resistance to FLT3 inhibitors in acute myeloid leukaemia cells.

BACKGROUND: Activating mutations in the Fms-like tyrosine kinase 3 (FLT3) are among the most prevalent oncogenic mutations in acute myeloid leukaemia. Inhibitors selectively targeting FLT3 kinase have shown promising clinical activity; their success in the clinic, however, has been limited due to the emergence of acquired resistance. METHODS: CCT245718 was identified and characterised as a dual Aurora A/FLT3 inhibitor through cell-based and biochemical assays. The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to FLT3 inhibitors. RESULTS: CCT245718 exhibits potent antiproliferative activity towards FLT3-ITD + AML cell lines and strongly binds to FLT3-ITD and TKD (D835Y) mutants in vitro. Activities of both FLT3-ITD and Aurora A are also inhibited in cells. Inhibition of FLT3 results in reduced phosphorylation of STAT5, downregulation of survivin and induction of apoptotic cell death. Moreover, CCT245718 overcomes TKD-mediated resistance in a MOLM-13-derived cell line containing FLT3 with both ITD and D835Y mutations. It also inhibits FLT3 signalling in both parental and resistant cell lines compared to FLT3-specific inhibitor MLN518, which is only active in the parental cell line. CONCLUSIONS: Our results demonstrate that CCT245718 is a potent dual FLT3/Aurora A inhibitor that can overcome TKD-mediated acquired resistance.

Reduction-Sensitive Dextran-Paclitaxel Polymer-Drug Conjugate: Synthesis, Self-Assembly into Nanoparticles, and In Vitro Anticancer Efficacy.

Delivery systems that can encapsulate a precise amount of drug and offer a spatiotemporally controlled drug release are being actively sought for safe yet effective cancer therapy. Compared to polymer nanoparticle (NP)-based delivery systems that rely on physical drug encapsulation, NPs derived from stimuli-sensitive covalent polymer-drug conjugates (PDCs) have emerged as promising alternatives offering precise control over drug dosage and spatiotemporal drug release. Herein, we report a reduction-sensitive PDC "Dex-SS-PTXL" synthesized by conjugating dextran and paclitaxel (PTXL) through a disulfide bond-bearing linker. The synthesized Dex-SS-PTXL PDC with a precise degree of substitution in terms of the percentage of repeat units of dextran covalently conjugated to PTXL (27 ± 0.6%) and the amount of drug carried by the PDC (39 ± 1.4 wt %) was found to self-assemble into spherical NPs with an average size of 110 ± 34 nm and a ζ-potential of -14.09 ± 8 mV. The reduction-sensitive Dex-SS-PTXL NPs were found to release PTXL exclusively in response to the reducing agent concentration reflective of the intracellular reducing environment of the tumor cells. Challenging BT-549 and MCF-7 cells with Dex-SS-PTXL NPs revealed significant cytotoxicity, while the IC50 values and the mode of action (mitotic arrest) of Dex-SS-PTXL NPs were found to be comparable to those of free PTXL, highlighting the active nature of the intracellularly released drug. The developed PDC with its unique ability to self-assemble into NPs and stimuli-responsive drug release can enhance the success of the NP-based drug delivery systems during clinical translation.

Natural and Semisynthetic Chalcones as Dual FLT3 and Microtubule Polymerization Inhibitors.

Activating mutations in FLT3 receptor tyrosine kinase are found in a third of acute myeloid leukemia (AML) patients and are associated with disease relapse and a poor prognosis. The majority of these mutations are internal tandem duplications (ITDs) in the juxtamembrane domain of FLT3, which have been validated as a therapeutic target. The clinical success of selective inhibitors targeting oncogenic FLT3, however, has been limited due to the acquisition of drug resistance. Herein the identification of a dual FLT3/microtubule polymerization inhibitor, chalcone 4 (2'-allyloxy-4,4'-dimethoxychalcone), is reported through screening of 15 related chalcones for differential antiproliferative activity in leukemia cell lines dependent on FLT3-ITD (MV-4-11) or BCR-ABL (K562) oncogenes and by subsequent screening for mitotic inducers in the HCT116 cell line. Three natural chalcones (1-3) were found to be differentially more potent toward the MV-4-11 (FLT3-ITD) cell line compared to the K562 (BCR-ABL) cell line. Notably, the new semisynthetic chalcone 4, which is a 2'-O-allyl analogue of the natural chalcone 3, was found to be more potent toward the FLT3-ITD+ cell line and inhibited FLT3 signaling in FLT3-dependent cells. An in vitro kinase assay confirmed that chalcone 4 directly inhibited FLT3. Moreover, chalcone 4 induced mitotic arrest in these cells and inhibited tubulin polymerization in both cellular and biochemical assays. Treatment of MV-4-11 cells with this inhibitor for 24 and 48 h resulted in apoptotic cell death. Finally, chalcone 4 was able to overcome TKD mutation-mediated acquired resistance to FLT3 inhibitors in a MOLM-13 cell line expressing FLT3-ITD with the D835Y mutation. Chalcone 4 is, therefore, a promising lead for the discovery of dual-target FLT3 inhibitors.

Synthesis and evaluation of novel α-substituted chalcones with potent anti-cancer activities and ability to overcome multidrug resistance.

A series of forty α-substituted chalcones were synthesized and screened for their antiproliferative activities against HCT116 (colorectal) and HCC1954 (breast) cancer cell lines. Compounds 5a and 5e were found to be the most potent compounds with GI50 values of 0.63 µM and 0.725 µM in HCC1954 cell line and 0.69 µM and 1.59 µM in HCT116 cell line, respectively. Both compounds induced a G2/M cell cycle arrest and caused apoptotic cell death in HCT116 cells as shown by the induction of PARP cleavage. The compounds also stabilized p53 in a dose-dependent manner in HCT116 cells following 24-hour treatment. Furthermore, both 5a and 5e were able to overcome multidrug resistance in two MDR-1 overexpressing multidrug resistant cell lines.

Biogenic Synthesis of AgNPs with Saussurea lappa C.B. Clarke and Studies on Their Biochemical Properties.

Nanotechnology has become an irreplaceable need and green synthesis of nanoparticles offers several advantages over physical and chemical methods. Medicinal plants are the main reservoirs of drugs and drug candidates. We report the biogenic synthesis of silver nanoparticles (AgNPs) using aqueous root extract of Saussurea lappa. Verification and characterization of these nanoparticles were done by UV-visible spectroscopy, XRD-analysis and Scanning Electron Microscopy and FT-IR. Extract-loaded-AgNPs showed the highest inhibition zone against Escherichia coli (11.0 mm) and intermediate against Pseudomonas aeruginosa (9.0 mm). The methanolic root extract of S. lappa alone, also moderately inhibited Pseudomonas aeruginosa (9.0 mm) and showed lower activity (6.0 mm) against Escherichia coli. Its aqueous roots extract inhibited (6.0 mm) the growth of tested organisms. Methanolic extract showed antioxidant potency (IC50 = 0.814 µg/mL). Experiments revealed the presence of phenols and flavonoids in the roots of Saussurea lappa. These findings provide promising interest to exploit Saussurea lappa for the biogenic synthesis of AgNPs and their biological applications.

Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. METHODS: To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. RESULTS: CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CONCLUSIONS: CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

Synthesis and evaluation of modified chalcone based p53 stabilizing agents.

Tumor suppressor protein p53 induces cell cycle arrest and apoptotic cell death in response to various cellular stresses thereby preventing cancer development. Activation and stabilization of p53 through small organic molecules is, therefore, an attractive approach for the treatment of cancers retaining wild-type p53. In this context, a series of nineteen chalcones with various substitution patterns of functional groups including chloro, fluoro, methoxy, nitro, benzyloxy, 4-methyl benzyloxy was prepared using Claisen-Schmidt condensation. The compounds were characterized using NMR, HRMS, IR and melting points. Evaluation of synthesized compounds against human colorectal (HCT116) and breast (CAL-51) cancer cell lines revealed potent antiproliferative activities. Nine compounds displayed GI50 values in the low micromolar to submicromolar range; for example (E)-1-phenyl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (SSE14108) showed GI50 of 0.473±0.043µM against HCT116 cells. Further analysis of these compounds revealed that (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (SSE14105) and (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (SSE14106) caused rapid (4 and 8-h post-treatment) accumulation of p53 in HCT116 cells similar to its induction by positive control, Nutlin-3. Such activities were absent in 3-(4-methoxyphenyl)propiophenone (SSE14106H2) demonstrating the importance of conjugated ketone for antiproliferative and p53 stabilizing activity of the chalcones. We further evaluated p53 levels in the presence of cycloheximide (CHX) and the results showed that the p53 stabilization was regulated at post-translational level through blockage of its degradation. These chalcones can, therefore, act as fragment leads for further structure optimization to obtain more potent p53 stabilizing agents with enhanced anti-proliferative activities.

7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent.

Introduction of a 1-benzyl-1H-pyrazol-4-yl moiety at C7 of the imidazo[4,5-b]pyridine scaffold provided 7a which inhibited a range of kinases including Aurora-A. Modification of the benzyl group in 7a, and subsequent co-crystallisation of the resulting analogues with Aurora-A indicated distinct differences in binding mode dependent upon the pyrazole N-substituent. Compounds 7a and 14d interact with the P-loop whereas 14a and 14b engage with Thr217 in the post-hinge region. These crystallographic insights provide options for the design of compounds interacting with the DFG motif or with Thr217.

Targeting the PPM1D phenotype; 2,4-bisarylthiazoles cause highly selective apoptosis in PPM1D amplified cell-lines.

The metal-dependent phosphatase PPM1D (WIP1) is an important oncogene in cancer, with over-expression of the protein being associated with significantly worse clinical outcomes. In this communication we describe the discovery and optimization of novel 2,4-bisarylthiazoles that phenocopy the knockdown of PPM1D, without inhibiting its phosphatase activity. These compounds cause growth inhibition at nanomolar concentrations, induce apoptosis, activate p53 and display impressive cell-line selectivity. The results demonstrate the potential for targeting phenotypes in drug discovery when tackling challenging targets or unknown mechanisms.

Chemical Synthesis of Selenium-containing Peptides.

Selenium (Se), a semi-metallic element, has chemical properties similar to sulfur; however, it has comparatively low electronegativity as well as a large atomic radius than sulfur. These features bestow selenium-containing compounds with extraordinary reactivity, sensitivity, and potential for several applications like chemical alteration, protein engineering, chemical (semi)synthesis, etc. Organoselenium chemistry is emerging fastly, however, examples of effective incorporation of Se into the peptides are relatively scarce. Providentially, there has been a drastic interest in synthesizing and applying selenoproteins and selenium-containing peptides over the last few decades. In this minireview, the synthetic methodologies of selenium-containing peptides and a brief description of their chemistry and biological activities are summarized. These methodologies enable access to various natural and unnatural selenium-containing peptides that have been used in a range of applications, from modulating protein characteristics to structure-activity relationship (SAR) studies for applications in nutraceuticals and drug development. This review aims at the audience interested in learning about the synthesis as well as will open new dimensions for their future research by aiding in the design of biologically interesting selenium-containing peptides.

Centrosome Clustering & Chemotherapy.

Centrosome abnormalities are the hallmark of cancer. How it affects tumorigenesis is still a mystery. However, the presence of more than two centrosomes at the onset of mitosis often leads to chromosomal instability and subsequent tumorigenesis. Unlike normal cells that undergo repair or apoptosis in response to this instability, cancer cells learn to cope with supernumerary centrosomes through various mechanisms and survive. Centrosome clustering is the most prevalent mechanism, allowing the cancer cells to form two daughter cells through a pseudo-bipolar spindle. Since healthy cells are devoid of the mechanisms involved in clustering, the de-clustering of centrosomes can be considered a promising approach to selectively eliminate cells with extra centrosomes. Several proteins such as PARP, KIFC1, Hsp70, Cortical actin, APC/C-CDH1 complex and Eg5 have been discussed in this review which participate in centrosome clustering, and the inhibition of these proteins can facilitate in impeding tumor growth specifically by declustering centrosomes. In this review, we also present the role of the centrosome in the cell cycle, centrosome amplification, clustering mechanism and reported centrosome de-clustering agents to present the current state of work in the field.

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy.

Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS). In healthy neutrophils, ROS plays an important role in pathogen killing by phagocytosis and by induction of Neutrophil Extracellular Traps (NETs). Given the key role of ROS in autophagy, phagocytosis and NETosis, the relationship between these pathways and the role of diabetes in the modulation of these pathways has not been explored previously. Therefore, our study aimed to understand the relationship between autophagy, phagocytosis and NETosis in diabetes. We hypothesized that hyperglycemia-associated oxidative stress alters the balance between phagocytosis and NETosis by modulating autophagy. Using whole blood samples from individuals with and without type 2-diabetes (in the presence and absence of hyperglycemia), we demonstrated that (i) hyperglycemia results in elevated levels of ROS in neutrophils from those with diabetes, (ii) elevated levels of ROS increase LCIII (a marker for autophagy) and downstream NETosis. (iii) Diabetes was also found to be associated with low levels of phagocytosis and phagocytic killing of S. pneumoniae. (iv) Blocking either NADPH oxidase or cellular pathways upstream of autophagy led to a significant reduction in NETosis. This study is the first to demonstrate the role of ROS in altering NETosis and phagocytosis by modulating autophagy in type 2-diabetes. GRAPHICAL ABSTRACT.

A Case Study of Depression in High Achieving Students Associated With Moral Incongruence, Spiritual Distress, and Feelings of Guilt.

Psychosocial and cultural factors play an important, but often neglected, role in depression in young individuals. In this article, we present two cases of young, educated males with major depressive disorder and prominent themes of guilt and spiritual distress. We explore the relationship between moral incongruence, spiritual distress, and feelings of guilt with major depressive episodes by presenting two cases of depression in young individuals who were high-achieving students. Both cases presented with low mood, psychomotor slowing, and selective mutism. Upon detailed history, spiritual distress and feelings of guilt due to internet pornographic use (IPU) and the resulting self-perceived addiction and moral incongruence were linked to the initiation and progression of major depressive episodes. The severity of the depressive episode was measured using the Hamilton Depression Scale (HAM-D). Themes of guilt and shame were measured using the State of Guilt and Shame Scale (SSGS). High expectations from the family were also a source of stress. Hence, it is important to keep these factors in mind while managing mental health problems in young individuals. Late adolescence and early adulthood are periods of high stress and vulnerabe to mental illness. Psychosocial determinants of depression in this age group generally go unexplored and unaddressed leading to suboptimal treatment, particularly in developing countries. Further research is needed to assess the importance of these factors and to determine ways to mitigate them.

Design, Synthesis, and Biological Evaluation of SSE1806, a Microtubule Destabilizer That Overcomes Multidrug Resistance.

Microtubules are dynamic structures that form spindle fibers during cell division; pharmacological inhibition of microtubule dynamics arrests cells in mitosis, leading to apoptosis, and they have been extensively used to treat various cancers. However, the efficacy of such drugs is often limited by multidrug resistance. This study synthesized and evaluated 30 novel derivatives of podophyllotoxin, a natural antimitotic compound, for their antiproliferative activities. Compound SSE1806 exhibited the most potent antiproliferative activity with GI50 values ranging from 1.29 ± 0.01 to 21.15 ± 2.1 µM in cancer cell lines of different origins; it directly inhibited microtubule polymerization, causing aberrant mitosis and G2/M arrest. Prolonged treatment with SSE1806 increased p53 expression, induced cell death in monolayer cultures, and reduced the growth of mouse- and patient-derived human colon cancer organoids. Importantly, SSE1806 overcame multidrug resistance in a cell line overexpressing MDR-1. Thus, SSE1806 represents a potential anticancer agent that can overcome multidrug resistance.

CT-MRI Dual Information Registration for the Diagnosis of Liver Cancer: A Pilot Study Using Point-based Registration.

BACKGROUND: Early diagnosis of liver cancer may increase life expectancy. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play a vital role in diagnosing liver cancer. Together, both modalities offer significant individual and specific diagnosis data to physicians; however, they lack the integration of both types of information. To address this concern, a registration process has to be utilized for the purpose, as multimodal details are crucial in providing the physician with complete information. OBJECTIVE: The aim was to present a model of CT-MRI registration used to diagnose liver cancer, specifically for improving the quality of the liver images and provide all the required information for earlier detection of the tumors. This method should concurrently address the issues of imaging procedures for liver cancer to fasten the detection of the tumor from both modalities. METHODS: In this work, a registration scheme for fusing the CT and MRI liver images is studied. A feature point-based method with normalized cross-correlation has been utilized to aid in the diagnosis of liver cancer and provide multimodal information to physicians. Data on ten patients from an online database were obtained. For each dataset, three planar views from both modalities were interpolated and registered using feature point-based methods. The registration of algorithms was carried out by MATLAB (vR2019b, Mathworks, Natick, USA) on an Intel (R) Core (TM) i5-5200U CPU @ 2.20 GHz computer. The accuracy of the registered image is being validated qualitatively and quantitatively. RESULTS: The results show that an accurate registration is obtained with minimal distance errors by which CT and MRI were accurately registered based on the validation of the experts. The RMSE ranges from 0.02 to 1.01 for translation, which is equivalent in magnitude to approximately 0 to 5 pixels for CT and registered image resolution. CONCLUSION: The CT-MRI registration scheme can provide complementary information on liver cancer to physicians, thus improving the diagnosis and treatment planning process.

Selenium-containing Peptides and their Biological Applications.

Selenium (Se) has been known for its beneficial biological roles for several years, but interest in this trace element has seen a significant increase in the past couple of decades. It has been reported to be a part of important bioactive organic compounds, such as selenoproteins and amino acids, including selenocysteine (SeCys), selenomethionine (SeMet), selenazolidine (SeAzo), and selenoneine. The traditional Se supplementations (primarily as selenite and selenomethionine), though have been shown to carry some benefits, also have associated toxicities, thereby paving the way for the organoselenium compounds, especially the selenoproteins and peptides (SePs/SePPs) that offer several health benefits beyond fulfilling the elementary nutritional Se needs. This review aims to showcase the applications of selenium-containing peptides that have been reported in recent decades. This article summarizes their bioactivities, including neuroprotective, antiinflammatory, anticancer, antioxidant, hepatoprotective, and immunomodulatory roles. This will offer the readers a sneak peek into the current advancements to invoke further developments in this emerging research area.