The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer.

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications andisomiRs that are predicted to target theALDH1,CD166,BMI1,LRIG1, andLGR5SC genes.miR-23bandmiR-92Aare of particular interest because our previously reported studies on miRNA expressionin isolated normal versus malignant human colonic SCs showed thatmiR-23bandmiR-92aareregulators of theLGR5andLRIG1SC genes, respectively. We also identify additional miRNAs whoseexpression inversely correlated with mRNA levels of their target genes and associated with CRCpatient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulationof SC genes could provide insight into how dysregulation of miRNAs leads to the emergence ofdifferent CSC populations and SC overpopulation in CRC

Bio-electrospraying 3-D Organotypic Human Skin Cultures

Organotypic 3D tissue models have greatly contributed to understand a wide range of molecular and cellular characteristics within a functional or diseased tissue. Human skin reconstructs which act as models are most useful for a wide range of investigations, ranging from tissue engineering and regenerative medicine, drug development, screening, and discovery to name a few. There are many approaches for reconstructing 3D skin tissue models, however, to date there have been very few that are able to generate organotypic 3D constructs with a single technology having minimal processing steps to finally scalability. The many manifestations of 3D bioprinting have contributed to this endeavor, having said that, the technology's limitations have tempered those reconstructed models, as they are known to contain low cell numbers/concentrations to those having damaged/dead molecules/cells within the reconstructed tissue, which are not desirable, for exploring as tissues models. Contrary to 3D bioprinting approaches, bio-electrosprays have been demonstrated to possess the ability to handle large concentrations of cells and molecules to whole fertilized embryos without damaging them from a molecular level upwards. Consequently, this article demonstrates, for the first time, bio-electrospray's capacity to reconstruct skin-like structures in vitro and its potential in reconstructing full-thickness 3D organotypic human skin tissues

A Mixed-Methods Study of Creative Problem Solving and Psychosocial Safety Climate: Preparing Engineers for the Future of Work

The future of work is forcing the world to adjust to a new paradigm of working. New skills will be required to create and adopt new technology and working methods. Additionally, cognitive skills, particularly creative problem-solving, will be highly sought after. The future of work paradigm has threatened many occupations but bolstered others such as engineering. Engineers must keep up to date with the technological and cognitive demands brought on by the future of work. Using an exploratory mixed-methods approach, our study sought to make sense of how engineers understand and use creative problem solving. We found significant associations between engineers’ implicit knowledge of creativity, exemplified creative problem solving, and the perceived value of creativity. We considered that the work environment is a potential facilitator of creative problem-solving. We used an innovative exceptional cases analysis and found that the highest functioning engineers in terms of knowledge, skills, and perceived value of creativity, also reported working in places that facilitate psychosocially safe environments to support creativity. We propose a new theoretical framework for a creative environment by integrating the Four Ps (Person, Process, Product, and Press) and psychosocial safety climate theory that management could apply to facilitate creative problem solving. Through the acquisition of knowledge to engage in creative problem solving as individuals or a team, a perception of value must be present to enforce the benefit of creativity to the engineering role. The future of work paradigm requires that organisations provide an environment, a psychosocially safe climate, for engineers to grow and hone their sought-after skills that artificial technologies cannot currently replace

Cellulosic fiber based hybrid composites: A comparative investigation into their structurally influencing mechanical properties

This paper focuses on hybrid and twisted hybrid Indian mallow/roselle cellulosic fiber yarn mat reinforced polyester composites and effects of their wood sawdust filler. The composite materials were fabricated using compression molding technique. There were four different combinations of hybrid yarn mat composite samples used, while the twisted hybrids were six. An evaluation of the hybrid and twisted hybrid mechanical properties for the single and double layer cases of the yarn mat was done with and without wood sawdust filler effects. The samples were tested at both warp and weft directions. From the results obtained at warp direction, it was observed that for the hybrid double layer case, longitudinal yarn mat with wood sawdust (filler) composite sample exhibited better tensile, impact and flexural strength properties in comparison with other related composites of hybrid type reported in literature. Moreover, the modified twisted hybrid double layer composites with longitudinal yarn mat and wood sawdust filler sample recorded significantly greater improvement on the mechanical properties at warp direction, when compared with the hybrid double layer longitudinal yarn mat composites with wood sawdust filler and other reported similar hybrid composite materials. Scanning electron microscopy (SEM) technique was utilized to evaluate morphological internal damage (cracks) and fractured surfaces of the various tested composite samples. Based on their mechanical performances and for further practical evidence, these two types of eco-composites were used to effectively fabricate tri-wheeler auto-wheel hubs and ceiling fan blades, as applicable to automobile and electronics industries, respectively.Peer reviewedFinal Accepted Versio

The v8-10 Variant Isoform of CD44 is Selectively Expressed in the Normal Human Colonic Stem Cell Niche and Frequently is Overexpressed in Colon Carcinomas During Tumor Development

CD44 protein and its variant isoforms are expressed in cancer stem cells (CSCs), and various CD44 isoforms can have different functional roles in cells. Our goal was to investigate how different CD44 isoforms contribute to the emergence of stem cell (SC) overpopulation that drives colorectal cancer (CRC) development. Specific CD44 variant isoforms are selectively expressed in normal colonic SCs and become overexpressed in CRCs during tumor development. We created a unique panel of anti-CD44 rabbit genomic antibodies to 16 specific epitopes that span the entire length of the CD44 molecule. Our panel was used to comprehensively investigate the expression of different CD44 isoforms in matched pairs (n = 10) of malignant colonic tissue and adjacent normal mucosa, using two (IHC & IF) immunostaining approaches. We found that: i) CD44v8-10 is selectively expressed in the normal human colonic SC niche; ii) CD44v8-10 is co-expressed with the SC markers ALDH1 and LGR5 in normal and malignant colon tissues; iii) colon carcinoma tissues frequently (80%) stain for CD44v8-10 while staining for CD44v6 was less frequent (40%). Given that CD44v8-10 expression is restricted to cells in the normal human colonic SC niche and CD44v8-10 expression progressively increases during CRC development, CD44v8-10 expression likely contributes to the SC overpopulation that drives the development and growth of colon cancers. Since the CD44 variant v8-10 epitope is located on CD44\u27s extracellular region, it offers great promise for targeted anti-CSC treatment approaches

Ethnomedical survey of plants used by the Orang Asli in Kampung Bawong, Perak, West Malaysia

<p>Abstract</p> <p>Background</p> <p>A qualitative ethnomedical survey was carried out among a local Orang Asli tribe to gather information on the use of medicinal plants in the region of Kampung Bawong, Perak of West Malaysia in order to evaluate the potential medicinal uses of local plants used in curing different diseases and illnesses.</p> <p>Methods</p> <p>Sixteen informants ranging in age from 35 to 65 years were interviewed. A total of 62 species of plants used by Orang Asli are described in this study based on field surveys and direct face to face communication. These plants belonged to 36 families and are used to treat a wide range of discomforts and diseases.</p> <p>Results</p> <p>The results of this study showed that majority of the Orang Asli, of Kampung Bawong are still dependent on local plants as their primary source of medication. As the first ethnomedical study in this area, publishing this work is expected to open up more studies to identify and assess the pharmacological and toxicological action of the plants from this region.</p> <p>Conclusions</p> <p>Preservation and recording of ethnobotanical and ethnomedical uses of traditional medicinal plants is an indispensable obligation for sustaining the medicinal and cultural resource of mankind. Extensive research on such traditional plants is of prime importance to scientifically validate their ethnomedical claims.</p

Induced Pluripotent Stem Cell-Derived Retinal Pigmented Epithelium: A Comparative Study Between Cell Lines and Differentiation Methods

PurposeThe application of induced pluripotent stem cell-derived retinal pigmented epithelium (iPSC-RPE) in patients with retinal degenerative disease is making headway toward the clinic, with clinical trials already underway. Multiple groups have developed methods for RPE differentiation from pluripotent cells, but previous studies have shown variability in iPSC propensity to differentiate into RPE.MethodsThis study provides a comparison between 2 different methods for RPE differentiation: (1) a commonly used spontaneous continuously adherent culture (SCAC) protocol and (2) a more rapid, directed differentiation using growth factors. Integration-free iPSC lines were differentiated to RPE, which were characterized with respect to global gene expression, expression of RPE markers, and cellular function.ResultsWe found that all 5 iPSC lines (iPSC-1, iPSC-2, iPSC-3, iPSC-4, and iPSC-12) generated RPE using the directed differentiation protocol; however, 2 of the 5 iPSC lines (iPSC-4 and iPSC-12) did not yield RPE using the SCAC method. Both methods can yield bona fide RPE that expresses signature RPE genes and carry out RPE functions, and are similar, but not identical to fetal RPE. No differences between methods were detected in transcript levels, protein localization, or functional analyses between iPSC-1-RPE, iPSC-2-RPE, and iPSC-3-RPE. Directed iPSC-3-RPE showed enhanced transcript levels of RPE65 compared to directed iPSC-2-RPE and increased BEST1 expression and pigment epithelium-derived factor (PEDF) secretion compared to directed iPSC-1-RPE. In addition, SCAC iPSC-3-RPE secreted more PEDF than SCAC iPSC-1-RPE.ConclusionsThe directed protocol is a more reliable method for differentiating RPE from various pluripotent sources and some iPSC lines are more amenable to RPE differentiation

Prevalence of intestinal parasitic infections among HIV patients in Benin City, Nigeria

This study was carried out to determine the presence of intestinal parasites and their correlation with CD4+ T-cell counts and demographics among human immunodeficiency virus (HIV)-positive patients in Benin City, Nigeria. Stool specimens from 2,000 HIV-positive patients and 500 controls (HIV-negative individuals) were examined for ova, cysts, or parasites, using standard procedures. In addition, patient's blood samples were analyzed for CD4 counts by flow cytometry. An overall prevalence rate of 15.3% was observed among HIV-positive patients while 6.2% was noted among non-HIV subjects. HIV status was a significant (P<0.0001) risk factor for acquiring intestinal parasitic infections. Male gender, CD4 count <200cell/µl, and diarrhea were significantly associated with an increased prevalence of intestinal parasitic infections among HIV-positive patients. The level of education, occupation, and source of water among HIV patients significantly (P<0.0001) affected the prevalence of intestinal parasitic infections. Ascaris lumbricoides was the most predominant parasite in both HIV-positive patients and controls. A CD4 count <200 cells/µl was significantly associated with only Isospora belli and Cryptosporidium infections. The presence of pathogenic intestinal parasites such as A. lumbricoides, hookworm, Giardia intestinalis, Entamoeba histolytica, Trichuris trichiura, and Taenia species among HIV-infected persons should not be neglected. Cryptosporidium species and I. belli were the opportunistic parasites observed in this study. Routine screening for intestinal parasites in HIV-positive patients is advocated

Increased Incidence of Vestibular Disorders in Patients With SARS-CoV-2

OBJECTIVE: Determine the incidence of vestibular disorders in patients with SARS-CoV-2 compared to the control population. STUDY DESIGN: Retrospective. SETTING: Clinical data in the National COVID Cohort Collaborative database (N3C). METHODS: Deidentified patient data from the National COVID Cohort Collaborative database (N3C) were queried based on variant peak prevalence (untyped, alpha, delta, omicron 21K, and omicron 23A) from covariants.org to retrospectively analyze the incidence of vestibular disorders in patients with SARS-CoV-2 compared to control population, consisting of patients without documented evidence of COVID infection during the same period. RESULTS: Patients testing positive for COVID-19 were significantly more likely to have a vestibular disorder compared to the control population. Compared to control patients, the odds ratio of vestibular disorders was significantly elevated in patients with untyped (odds ratio [OR], 2.39; confidence intervals [CI], 2.29-2.50; CONCLUSIONS: The incidence of vestibular disorders differed between COVID-19 variants and was significantly elevated in COVID-19-positive patients compared to the control population. These findings have implications for patient counseling and further research is needed to discern the long-term effects of these findings