Phylogenomics of Scorpions Reveal Contemporaneous Diversification of Scorpion Mammalian Predators and Mammal-Active Sodium Channel Toxins.

Scorpions constitute a charismatic lineage of arthropods and comprise more than 2500 described species. Found throughout various tropical and temperate habitats, these predatory arachnids have a long evolutionary history, with a fossil record that began in the Silurian. While all scorpions are venomous, the asymmetrically diverse family Buthidae harbors nearly half the diversity of extant scorpions, and all but one of the 58 species that are medically significant to humans. However, the lack of a densely sampled scorpion phylogeny has hindered broader inferences of the diversification dynamics of scorpion toxins. To redress this gap, we assembled a phylogenomic data set of 100 scorpion venom gland transcriptomes and genomes, emphasizing the sampling of highly toxic buthid genera. To infer divergence times of venom gene families, we applied a phylogenomic node dating approach for the species tree in tandem with phylostratigraphic bracketing to estimate the minimum ages of mammal-specific toxins. Our analyses establish a robustly supported phylogeny of scorpions, particularly with regard to relationships between medically significant taxa. Analysis of venom gene families shows that mammal-active sodium channel toxins (NaTx) have independently evolved in five lineages within Buthidae. Temporal windows of mammal-targeting toxin origins are correlated with the basal diversification of major scorpion mammal predators such as shrews, bats, and rodents. These results suggest an evolutionary model of relatively recent diversification of buthid NaTx homologs in response to the diversification of scorpion predators. [Adaptation; arachnids; phylogenomic dating; phylostratigraphy; venom.].

Possible Protective Potency of Argun Nut (Medemia argun - An Ancient Egyptian Palm) against Hepatocellular Carcinoma in Rats.

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Medemia argun (MA) fruits have been found to possess proanthocyanidins (PACs), having antioxidant activity. Methods: Intraperitoneal (IP) diethyl nitrosamine (DENA; 200 mg/kg, once) and carbon tetra chloride (CCl4, 3 ml/kg/week, subcutaneously, for 6 weeks) induced HCC in rats. Animals groups: Group I; received vehicle (control). Group II; received MA seed extract, 100 mg/kg (twice/week) for 12 weeks, IP. Group III; received carcinogenic agents only. Group IV; received MA for two weeks before administration of DENA/CCl4 till the end of the experiment. The total period of the experiment was three months. Results: DENA and CCl4 induced HCC, elevated serum alpha-fetoprotein (AFP), liver size, weight, tissue lymphocytic infiltration, nuclear/cytoplasmic ratio, collagen fiber and polysaccharide deposition, cellular proliferation, excessive pro-apoptotic caspase-3 accumulation, disrupted apoptosis. MA prior to DENA/CCl4, significantly protected liver against cancer progression, indicated by serum enzymes, antioxidant markers(glutathione, nitric oxide, and depressed malondialdehyde contents) in the MA-pretreated group, compared to the HCC one, without apparent useful action on superoxide dismutase activity, enhanced apoptosis in liver, through increased casapase-3 expression. The HCC group showed decreased antioxidant defense and BAX/Bcl-2 ratio. Conclusions: This study assumes that MA has a chemo-preventive effect against hepatocarcinogenesis.

Highly Pathogenic Avian Influenza Virus (H5N8) Clade 2.3.4.4 Infection in Migratory Birds, Egypt.

We isolated highly pathogenic avian influenza virus (H5N8) of clade 2.3.4.4 from the common coot (Fulica atra) in Egypt, documenting its introduction into Africa through migratory birds. This virus has a close genetic relationship with subtype H5N8 viruses circulating in Europe. Enhanced surveillance to detect newly emerging viruses is warranted.

Progressive glycosylation of the haemagglutinin of avian influenza H5N1 modulates virus replication, virulence and chicken-to-chicken transmission without significant impact on antigenic drift.

Highly pathogenic H5N1 avian influenza virus (A/H5N1) devastated the poultry industry and continues to pose a pandemic threat. Studying the progressive genetic changes in A/H5N1 after long-term circulation in poultry may help us to better understand A/H5N1 biology in birds. A/H5N1 clade 2.2.1.1 antigenic drift viruses have been isolated from vaccinated commercial poultry in Egypt. They exhibit a peculiar stepwise accumulation of glycosylation sites (GS) in the haemagglutinin (HA) with viruses carrying, beyond the conserved 5 GS, additional GS at amino acid residues 72, 154, 236 and 273 resulting in 6, 7, 8 or 9 GS in the HA. Available information about the impact of glycosylation on virus fitness and pathobiology is mostly derived from mammalian models. Here, we generated recombinant viruses imitating the progressive acquisition of GS in HA and investigated their biological relevance in vitro and in vivo. Our in vitro results indicated that the accumulation of GS correlated with increased glycosylation, increased virus replication, neuraminidase activity, cell-to-cell spread and thermostability, however, strikingly, without significant impact on virus escape from neutralizing antibodies. In vivo, glycosylation modulated virus virulence, tissue tropism, replication and chicken-to-chicken transmission. Predominance in the field was towards viruses with hyperglycosylated HA. Together, progressive glycosylation of the HA may foster persistence of A/H5N1 by increasing replication, stability and bird-to-bird transmission without significant impact on antigenic drift.

Surveillance on A/H5N1 virus in domestic poultry and wild birds in Egypt.

BACKGROUND: The endemic H5N1 high pathogenicity avian influenza virus (A/H5N1) in poultry in Egypt continues to cause heavy losses in poultry and poses a significant threat to human health. METHODS: Here we describe results of A/H5N1 surveillance in domestic poultry in 2009 and wild birds in 2009-2010. Tracheal and cloacal swabs were collected from domestic poultry from 22024 commercial farms, 1435 backyards and 944 live bird markets (LBMs) as well as from 1297 wild birds representing 28 different types of migratory birds. Viral RNA was extracted from a mix of tracheal and cloacal swabs media. Matrix gene of avian influenza type A virus was detected using specific real-time reverse-transcription polymerase chain reaction (RT-qPCR) and positive samples were tested by RT-qPCR for simultaneous detection of the H5 and N1 genes. RESULTS: In this surveillance, A/H5N1 was detected from 0.1% (n = 23/) of examined commercial poultry farms, 10.5% (n = 151) of backyard birds and 11.4% (n = 108) of LBMs but no wild bird tested positive for A/H5N1. The virus was detected from domestic poultry year-round with higher incidence in the warmer months of summer and spring particularly in backyard birds. Outbreaks were recorded mostly in Lower Egypt where 95.7% (n = 22), 68.9% (n = 104) and 52.8% (n = 57) of positive commercial farms, backyards and LBMs were detected, respectively. Higher prevalence (56%, n = 85) was reported in backyards that had mixed chickens and waterfowl together in the same vicinity and LBMs that had waterfowl (76%, n = 82). CONCLUSION: Our findings indicated broad circulation of the endemic A/H5N1 among poultry in 2009 in Egypt. In addition, the epidemiology of A/H5N1 has changed over time with outbreaks occurring in the warmer months of the year. Backyard waterfowl may play a role as a reservoir and/or source of A/H5N1 particularly in LBMs. The virus has been established in poultry in the Nile Delta where major metropolitan areas, dense human population and poultry stocks are concentrated. Continuous surveillance, tracing the source of live birds in the markets and integration of multifaceted strategies and global collaboration are needed to control the spread of the virus in Egypt.

Isolation of H9N2 avian influenza virus from bobwhite quail (Colinus virginianus) in Egypt.

This study describes the first isolation of H9N2 avian influenza virus (AIV) from commercial bobwhite quail (Colinus virginianus) in Egypt. Infected birds showed neither clinical signs nor mortality. Virus isolation and real-time reverse transcription polymerase chain reaction confirmed the presence of the H9N2 virus in cloacal swab samples collected at 35 days of age and the absence of other AIV subtypes, including H5 and H7. The hemagglutinin and neuraminidase genes of the isolated virus showed 99.1% and 98.2% nucleotide identity and 97.3% and 100% amino acid identity, respectively, to those of H9N2 viruses currently circulating in poultry in the Middle East. Phylogenetically, the Egyptian H9N2 virus was closely related to viruses of the G1-like lineage isolated from neighbouring countries, indicating possible epidemiological links.

Distribution of avian influenza H5N1 viral RNA in tissues of AI-vaccinated and unvaccinated contact chickens after experimental infection.

Avian influenza due to highly pathogenic avian influenza (HPAIV) H5N1 virus is not a food-borne illness but a serious panzootic disease with the potential to be pandemic. In this study, broiler chickens were vaccinated with commercial H5N1 or H5N2 inactivated vaccines prior to being challenged with an HPAIV H5N1 (clade 2.2.1 classic) virus. Challenged and non-challenged vaccinated chickens were kept together, and unvaccinated chickens served as contact groups. Post-challenge samples from skin and edible internal organs were collected from dead and sacrificed (after a 14-day observation period) birds and tested using qRT-PCR for virus detection and quantification. H5N1 vaccine protected chickens against morbidity, mortality and transmission. Virus RNA was not detected in the meat or edible organs of chickens vaccinated with H5N1 vaccine. Conversely, H5N2 vaccine did not confer clinical protection, and a significant virus load was detected in the meat and internal organs. Phylogenetic analysis showed that the H5N1 virus vaccine and challenge virus strains are closely related. The results of the present study strongly suggest a need for proper selection of vaccines and their routine evaluation against newly emergent field viruses. These actions will help to reduce human exposure to HPAIV H5N1 virus from both infected live birds and slaughtered poultry. In addition, rigorous preventive measures should be put in place in order to minimize the public-health risks of avian influenza at the human-animal interface.

Diversifying evolution of highly pathogenic H5N1 avian influenza virus in Egypt from 2006 to 2011.

An evolutionary analysis was conducted of 354 hemagglutinin (HA) and 208 neuraminidase (NA) genes, including newly generated sequences of 5 HA and 30 NA, of Egyptian H5N1 clade 2.2.1 viruses isolated from poultry and humans. Five distinct phylogenetically distinguishable clusters arose from a monophyletic origin since 2006. Only two clusters remained in circulation after 2009: (i) A cluster of viruses arose in 2007 in industrial-vaccinated chickens and carried multiple mutations in or adjacent to the immunogenic epitopes of the HA. Viruses within this cluster evolved with significantly elevated mutation rates indicating persisting selective pressures, e.g. to escape host immunity and (ii) The second group arose in 2008 and harboured strains from recent human infections featuring a conspicuous deletion in the HA receptor-binding domain and substitutions close to the highly conserved active site of the NA. In both sublineages, a number of positively selected amino acids, different glycosylation patterns and variations in the polybasic proteolytic cleavage site were observed. Continuous monitoring of the evolving H5N1 virus in Egypt is essential to develop new control campaigns in poultry and human population.

A Comparative Study to Evaluate the Essential Work of Fracture to Measure the Fracture Toughness of Quasi-Brittle Material.

In the present work, three different woven composite laminates were fabricated using the hand lay-up method. The woven reinforcement fibres were carbon fibres (CFRP), glass fibres (GFRP-W) and (GFRP-R) in combination with epoxy resin. Then, the central notch specimen tensile test (CNT) was used to measure the fracture toughness and the corresponding surface release energy (GIC). Then, the data were compared with the essential work of fracture (we) values based on the stored energy of the body to obtain a new standard fracture toughness test for composite laminates using relatively simple techniques. In addition to an extended finite element model, XFEM was implemented over a central notch specimen geometry to obtain a satisfactory validation of the essential work of fracture concepts. Therefore, the average values of (GIC) were measured with CNT specimens 25.15 kJ/m2, 32.5 kJ/m2 and 20.22 kJ/m2 for CFRP, GFRP-W and GFRP-R, respectively. The data are very close as the percentage error for the surface release energy measured by the two methods was 0.83, 4.6 and 5.16 for carbon, glass and random fibre composite laminates, respectively. The data for the fracture toughness of XFEM are also very close. The percentage error is 4.6, 5.25 and 2.95 for carbon, glass and random fibre composite laminates, respectively. Therefore, the fundamental work of the fracture concept is highly recommended as a fracture toughness test for composite laminates or quasi-brittle Material.

Reducing zoonotic avian influenza transmission at household poultry slaughter using a behaviour change tool for limited literacy audiences.

Human infections in Egypt with highly pathogenic avian influenza (HPAI) likely due to airborne transmission of HPAI virus (HPAIV) during home slaughter of poultry predominately affect women and children, who are the primary caregivers of household poultry. This study developed a safe contained poultry slaughter procedure to reduce airborne HPAIV and zoonotic infections and simultaneously created an educational outreach tool for teaching the modified procedure. The tool designed for limited literacy audiences used two illustrated posters and handouts for teaching the safe contained poultry slaughter procedure. The posters were developed with advice of animal health professionals and then refined by target audience women's focus groups. These women's focus groups proved to be the critical step for assuring the understanding, acceptance, effectiveness and accuracy of the outreach tool. The safe contained poultry slaughter procedure was designed to be low or no cost, sustainable by using a universal implement found in village households and designed as a minor variation of standard poultry halal slaughter. It was crafted to be culturally appropriate and religiously acceptable.

Investigation of Erosion/Corrosion Behavior of GRP under Harsh Operating Conditions.

Glass-fiber-reinforced pipe (GRP) is a strong alternative to many other materials, such as cast iron and concrete. It is characterized by high corrosion resistance, resulting in good erosion/corrosion. For the erosion/corrosion test, commercially available GRPs were used, which are frequently utilized for oil field wastewater in harsh environments. This type of GRP material was subjected to simulated conditions replicating in situ or harsh environments. An extensive experiment was conducted. Three quantities of abrasive sand (250 g, 400 g and 500 g with a size of 65 µm) were mixed with 0.015 m3 of water. The abrasive sand samples were taken at a 90 degree angle from the wall of the cylinder tubes. Three flow rate conditions were selected, 0.01 m3/min, 0.0067 m3/min and 0.01 m3/min, with 10 wt.% chlorine. Furthermore, these tests were conducted at five different times: 1 h, 2 h, 3 h, 4 h and 5 h. The results show that the erosion rate increased both with an increasing amount of abrasive sand and with increasing flow rate. The maximum value for the erosion rate was more than three for a flow rate of 0.015 m3 with chlorine for 500 g of sand. The corrosion rate also showed the same trend, with the maximum corrosion rate being reached under the same conditions. It was found that the corrosion rate largely depends on the amount of weight loss, which is an indicator of the erosion effect. Therefore, GFRP provides better erosion/corrosion resistance in a harsh environment or in situ conditions.

High prevalence of multiple human papillomavirus infection in Japanese patients with invasive uterine cervical cancer.

OBJECTIVE: Multiple human papillomavirus (HPV) infection of the uterine cervix has been suggested as a risk factor for persistent HPV infection, resulting in the development of invasive cervical cancer. The aim of this study was to reveal the actual state of multiple HPV infection in Japanese patients with invasive cervical cancer. METHODS: Sixty fresh-frozen invasive cervical cancer tissues were examined for genotyping of HPV. The presence of HPV genotypes was determined with an HPV-DNA array, which can discriminate 25 different HPV genotypes with high sensitivity and specificity. RESULTS: Among 60 samples, 59 (96.7%) were positive for HPV. The three common genotypes were HPV-16 (83.3%), HPV-18 (45.0%) and HPV-52 (28.3%). Multiple HPV infection was observed in 47 of 60 samples (78.3%), among which 42 were infected with more than one high-risk genotype (70.0%). Multiple high-risk HPV infection was significantly more prevalent in patients below 40 years old (14/15, 93.3%) than in patients 40 years of age and over (28/45, 62.2%). CONCLUSION: The HPV-DNA array is the preferred method to detect HPV genotypes. Multiple HPV infection in Japanese patients with invasive cervical cancer seemed to be more frequent than reported in the literature.

Cyclic Relaxation, Impact Properties and Fracture Toughness of Carbon and Glass Fiber Reinforced Composite Laminates.

In this paper, the mechanical properties of fiber-reinforced epoxy laminates are experimentally tested. The relaxation behavior of carbon and glass fiber composite laminates is investigated at room temperature. In addition, the impact strength under drop-weight loading is measured. The hand lay-up technique is used to fabricate composite laminates with woven 8-ply carbon and glass fiber reinforced epoxy. Tensile tests, cyclic relaxation tests and drop weight impacts are carried out on the carbon and glass fiber-reinforced epoxy laminates. The surface release energy GIC and the related fracture toughness KIC are important characteristic properties and are therefore measured experimentally using a standard test on centre-cracked specimens. The results show that carbon fiber-reinforced epoxy laminates with high tensile strength give high cyclic relaxation performance, better than the specimens with glass fiber composite laminates. This is due to the higher strength and stiffness of carbon fiber-reinforced epoxy with 600 MPa compared to glass fiber-reinforced epoxy with 200 MPa. While glass fibers show better impact behavior than carbon fibers at impact energies between 1.9 and 2.7 J, this is due to the large amount of epoxy resin in the case of glass fiber composite laminates, while the impact behavior is different at impact energies between 2.7 and 3.4 J. The fracture toughness KIC is measured to be 192 and 31 MPa √m and the surface energy GIC is measured to be 540.6 and 31.1 kJ/m2 for carbon and glass fiber-reinforced epoxy laminates, respectively.

Assessment of the Corrosion Behavior of Friction-Stir-Welded Dissimilar Aluminum Alloys.

The fuel consumption of high-density automobiles has increased in recent years. Aluminum (Al) alloy is a suitable material for weight reduction in vehicles with high ductility and low weight. To address environmental problems in aircraft and maritime applications, in particular rust development and corrosion, the current study assesses the corrosion behavior during friction stir welding (FSW) of two dissimilar Al alloys (AA6061 and AA8011) in various corrosive conditions using salt spraying and submersion tests. Two acidic solutions and one alkaline solution are used in these tests, which are performed at room temperature. The two specimens (AA6061 and AA8011) and the weld region are suspended in a salt spraying chamber and a 5 wt.% NaCl solution is continually sprayed using the circulation pump for 60 h, with the specimens being weighed every 15 h to determine the corrosion rates. According to the salt spraying data, the weld zone has a higher corrosion resistance than the core components. For twenty-eight days, individual specimens are submerged in 3.5 wt.% HCl + H2O and H2SO4 + H2O solutions and seawater. The weld area specimens exhibit stronger corrosion resistance than the base material specimens, and weight loss in the saltwater medium is lower when compared to the other test solutions, according to the corrosion analysis. The scanning electron microscope (SEM) analysis demonstrates that the base metal AA8011 is considerably corroded on its surface.

Alkali-Treated Titanium Coated with a Polyurethane, Magnesium and Hydroxyapatite Composite for Bone Tissue Engineering.

The aim of this study was to form a functional layer on the surface of titanium (Ti) implants to enhance their bioactivity. Layers of polyurethane (PU), containing hydroxyapatite (HAp) nanoparticles (NPs) and magnesium (Mg) particles, were deposited on alkali-treated Ti surfaces using a cost-effective dip-coating approach. The coatings were assessed in terms of morphology, chemical composition, adhesion strength, interfacial bonding, and thermal properties. Additionally, cell response to the variably coated Ti substrates was investigated using MC3T3-E1 osteoblast-like cells, including assessment of cell adhesion, cell proliferation, and osteogenic activity through an alkaline phosphatase (ALP) assay. The results showed that the incorporation of HAp NPs enhanced the interfacial bonding between the coating and the alkali-treated Ti surface. Furthermore, the presence of Mg and HAp particles enhanced the surface charge properties as well as cell attachment, proliferation, and differentiation. Our results suggest that the deposition of a bioactive composite layer containing Mg and HAp particles on Ti implants may have the potential to induce bone formation.

A Novel and Highly Effective Natural Vibration Modal Analysis to Predict Nominal Strength of Open Hole Glass Fiber Reinforced Polymer Composites Structure.

Glass fiber reinforced polymer (GFRP) composite laminates are considered the key material in many industries such as the infrastructure industries and the aerospace sector, and in building structures due to their superior specific strength and lightweight properties. The prediction of specimens' nominal strength with open holes is still an attractive and questionable field of study. The specimen size effect is referred to its strength degradation due to the presence of holes when specimen geometry gets scaled. The non-destructive test used to measure the nominal strength of such material is a great tool for fast selection purposes, but not secure enough for several purposes. Furthermore, the destructive tests which are more expensive and time-consuming should be avoided in such structures. The present work aims to predict the nominal strength of open-hole GFRP's composite using modal analysis of their natural frequency as non-destructive tests. At this end, the natural frequency, which is measured using modal analysis procedures, is combined with both linear elastic fracture mechanics (LEFM) and the theory of elasticity to predict the nominal strength of open-hole composite laminates. This advanced model employs two parameters of surface release energy resulting from a simple tension test and Young's modulus based on vibration modal analysis. It is well established that these types of materials are also subjected to a size effect in dynamic response. Inversely to the known static loading size effect, the size effect in dynamic response increases with specimen size. The novel model gives excellent and acceptable results when compared with experimental and finite element ones. Size effects curves of a nominal strength of these laminates have a very close relative value with those obtained from finite element and analytical modeling. Moreover, the received design tables and graphs would be highly applicable when selecting suitable materials for similar industrial applications.

Epigenetic modulation of autophagy genes linked to diabetic nephropathy by administration of isorhamnetin in Type 2 diabetes mellitus rats.

Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes (FYCO1, ULK, TECPR1 and WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes. Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.

Integrative microRNA and gene expression analysis identifies new epigenetically regulated microRNAs mediating taxane resistance in ovarian cancer.

Taxane is a family of front-line chemotherapeutic agents against ovarian cancer (OC). The therapeutic efficacy is frequently counteracted by the development of chemoresistance, leading to high rates of relapse in OC patients. The role(s) of microRNAs (miRNAs) in cancer chemoresistance had been supported by many evidences Epigenetic regulation by miRNAs has been reported to influence cancer development and response to therapeutics, however, their role in OC resistance to paclitaxel (PTX) is unclear. Here, we conducted miRNA profiling in the responsive and PTX-resistant OC cell lines before and after treatment with epigenetic modulators. We reveal 157 miRNAs to be downregulated in the PTX-resistant cells compared to parental controls. The expression of five miRNAs (miRNA-7-5p, -204-3p, -501-5p, -3652 and -4286) was restored after epigenetic modulation, which was further confirmed by qPCR. In silico analysis of the signaling pathways targeted by the selected miRNAs identified the PI3K-AKT pathway as the primary target. Subsequent cDNA array analysis confirmed multiple PI3K-AKT pathway members such as AKT2, PIK3R3, CDKN1A, CCND2 and FGF2 to be upregulated in PTX-resistant cells. STRING analysis showed the deregulated genes in PTX-resistant cells to be primarily involved in cell cycle progression and survival. Thus, high throughput miRNA and cDNA profiling coupled with pathway analysis and data mining provide evidence for epigenetically regulated miRNAs-induced modulation of signaling pathways in PTX resistant OC cells. It paves the way to more in-depth mechanistic studies and new therapeutic strategies to combat chemoresistance.

Novel Bis-Thiazole Derivatives: Synthesis and Potential Cytotoxic Activity Through Apoptosis With Molecular Docking Approaches.

A series of bis-thiazoles 5a-g were synthesized from bis-thiosemicarbazone 3 with hydrazonoyl chlorides 4a-g. Reaction of 3 with two equivalents of α-halocarbonyl compounds 6-8, 10, and 12a-d afforded the corresponding bis-thiazolidines 9, 11, and 13a-d, respectively. Condensation of bis-thiazolidin-4-one 9 with different aromatic aldehydes furnished bis-thiazolidin-4-ones 14a-d. Compounds 5a-g, 9, and 13a,c,d were screened in vitro for their cytotoxic activities in a panel of cancer cell lines. Compounds 5a-c, 5f-g, and 9 exhibited remarkable cytotoxic activities, especially compound 5c with potent IC50 value 0.6 nM (against cervical cancer, Hela cell line) and compound 5f with high IC50 value 6 nM (against ovarian cancer, KF-28 cell line). Compound 5f-induced appreciated apoptotic cell death was measured as 82.76% associated with cell cycle arrest at the G1 phase. The apoptotic pathways activated in KF-28 cells treated with 5a, 5b, and 5f were further investigated. The upregulation of some pro-apoptotic genes, bax and puma, and the downregulation of some anti-apoptotic genes including the Bcl-2 gene were observed, indicating activation of the mitochondrial-dependent apoptosis. Together with the molecular docking studies of compounds 5a and 5b, our data revealed potential Pim-1 kinase inhibition through their high binding affinities indicated by inhibition of phosphorylated C-myc as a downstream target for Pim-1 kinase. Our study introduces a set of bis-thiazoles with potent anti-cancer activities, in vitro.