Open Access Pub publishes peer-reviewed, free-to-read open-access articles. Showing
articles matching differentiation — open any to read the full text,
or download the PDF or XML.
Feb 2022 DOI 10.14302/issn.2379-8572.joa-22-4072
This translational paper discusses differentiation‑stage factors from zebrafish embryos as epigenetic regulators with potential to reverse neurosensory hearing loss. It outlines experimental evidence, delivery concepts, and research gaps.
Mar 2024 DOI 10.14302/issn.2689-4602.jes-24-4982
Mammalian Rbm45 is predominately expressed in neuronal tissue and is integral in brain development and neuronal differentiation under physiological conditions. Dysregulation of Rbm45 has been strongly associated with neurodegenerative disorders in humans and can drive hepatocellular carcinoma through reprogramming lipid metabolism. Intriguingly, Rbm45 is an ancient protein, evolutionarily conserved throughout metazoans, including in sponges which lack a nervous system. Curiously, the evolution of Rbm45 gene structure and protein domain conservation across kingdom Animalia is largely unknown. We performed phylogenetic analysis of Rbm45 nucleotide and amino acid sequences from 36 species representing 9 phyla: Porifera, Cnidaria, Priapulida, Mollusca, Brachiopoda, Arthropoda, Echinodermata, Hemichordata, and Chordata. While the tree from Rbm45 nucleotide sequence data resulted in clades Protostomia and Deuterostomia showing paraphyly, the phylogeny derived from Rbm45 amino acid sequence largely recapitulated known monophyletic relationships among metazoans. Human RBM45 protein structure includes three RNA-binding domains (RBD), a homo-oligomerization association (HOA) domain, a nuclear localization sequence (NLS), and a nuclear export sequence (NES). Multiple sequence alignment across the same 36 taxa used for phylogenetic analysis revealed conservation of all three RBDs, the HOA, and NLS; in contrast the NES was only detected in clade Craniata and not in clades Ambulacraria and Protostomia. Rbm45 gene structure analysis revealed increasing gene complexity concomitant with increasing evolutionary complexity. Rbm45 from non-bilaterian taxa had from 2 to 4 large exons, while bilaterian taxa had between 6 to17 small exons. These findings demonstrate that Rbm45 is an ancient, highly conserved gene among metazoans suggesting a function in a breadth of neural/sensory systems.
Feb 2024 DOI 10.14302/issn.2643-6655.jcap-24-4898
The structuring of one’s own identity is a fundamental and demanding evolutionary task of adolescence. The positive resolution of this task, that is the acquisition of a healthy and integrated identity, is closely linked to adolescents’ ability to develop one’s own Life Story, namely an internalized and evolving self-story. The structuring of one’s own identity, which is the foundation of positive development, requires adolescents to develop a good level of mental functioning and access to autobiographical memory. This work aims to deepen the importance of mental functions and autobiographical memory in the development of adolescents’ identity and life story and, accordingly, in preventing identity diffusion, aggressiveness and depression among adolescents. Specifically, given their relevance in relation to this, it has been decided to examine the mental functions of 1) Differentiation and Integration, 2) Mentalization and Reflexive function and 3) Meaning and directionality and the Self defining memories, a particular class of autobiographical memories.
Nov 2023
Uroscopy is the first documented laboratory test in medicine and is a fundamental diagnostic tool in the Unani system of medicine. Proper sample collection, handling, and identification are important to insure valid results in uroscopy.There are certain do’s and don’ts about the sampling mentioned in the text of the Unani medicine that should be followed. Generally, a urine sample is collected by the patient himself or herself, hence they must be educated to avoid contamination to ensure the purity of the sample. Despite this, there is a chance for error or malpractice hence collected samples should be identified for sufficiency and originality. There is a certain factor that can cause an erroneous result that must be avoided. Unani scholars have mentioned that sometimes patients brought other similar fluids or animal urine to test the competence of the physician or to mislead the diagnosis. To deal with such a situation differentiation of urine with other liquors should be made. The method of sample collection and identification for uroscopy are systematically summarized in this paper.
Mar 2023 DOI 10.14302/issn.2766-8630.jrnm-22-4093
Attenuation differences from 2 x-ray sources allow differentiation and characterization of stone types with similar radiation dose compared to single-energy CT scan. The difference is shown in colours, allowing preoperative prediction and management of stones. We determined the effect of DECT-KUB on urological management of patients with uric acid stones since it was first introduced in our centre. 50 patients with uric acid stones were selected from 2 year groups, each with 25 patients and their urological managements were reviewed retrospectively. We concluded that DECT-KUB is an accurate way of determining the chemical characteristics of renal calculi and can alter patients’ management. It has gained wide acceptance among clinicians in our centre and is now widely used to plan urological management of patients with renal calculi. Based on urological management comparison of patients who presented in the year 2011 with uric acid stones and patients in the year 2020, we concluded that patients with uric acid stones based on DECT-KUB findings can start dissolution therapy instead of surgical extraction or lithotripsy prior to biochemical analysis results become available. Although utility of DECT-KUB is widely accepted among clinicians in our centre it may not be available worldwide and this is the limiting factor in its universal use.
Apr 2022 DOI 10.14302/issn.2689-5773.jcdp-22-4123
Background Thyroid benign (TBN) and malignant (TMN) nodules are a common thyroid lesion. The differentiation of TMN often remains a clinical challenge and further improvements of TMN diagnostic accuracy are warranted. The aim of present study was to evaluate possibilities of using differences in trace elements (TEs) contents in nodular tissue for diagnosis of thyroid malignancy. Methods Contents of TEs such as silver (Ag), aluminum (Al), boron (B),, beryllium (Be), bismuth (Bi), cadmium (Cd), cerium (Ce), cobalt (Co), chromium (Cr), cesium (Cs), iron (Fe), gallium (Ga), mercury (Hg), iodine (I), lanthanum (La), lithium (Li), manganese (Mn), molybdenum (Mo), neodymium (Nd), nickel (Ni), lead (Pb), praseodymium (Pr), rubidium (Rb), antimony (Sb), scandium (Sc), selenium (Se), samarium (Sm), tin (Sn), thallium (Tl), uranium (U), yttrium (Y), and zinc (Zn) were prospectively evaluated in nodular tissue of thyroids with TBN (79 patients) and to TMN (41 patients). Measurements were performed using a combination of non-destructive instrumental neutron activation analysis with high resolution spectrometry of short- and long-lived radionuclides (INAA-SLR and INAA-LLR, respectively) and destructive method such as inductively coupled plasma mass spectrometry (ICP-MS). Results It was observed that in TMN tissue the mean mass fractions of Be, Fe, I, Sc, and Se are approximately 1.9, 1.7, 14, 3.1, and 1.6 times, respectively, lower while the mass fraction of Ga, Mo, and Rb 62%, 51%, and 33%, respectively, higher than those in TBN tissue. Contents of Ag, Al, B, Bi, Cd, Ce, Co, Cr, Cs, Hg, La, Li, Mn, Nd, Ni, Pb, Pr, Sb, Sm, Sn, Tl, U, Y, and Zn found in the TBN and TMN groups of nodular tissue samples were similar. Conclusions It was proposed to use the I mass fraction, as well as I/Ga, I/Mo, and I/Rb mass fraction ratios in a needle-biopsy of thyroid nodules as a potential tool to diagnose thyroid malignancy. Further studies on larger number of samples are required to confirm our findings and proposals.
Nov 2021 DOI 10.14302/issn.2690-4837.ijip-21-4015
Copper (Cu) has a strong impact on the function of the immune system through several different pathways. These impacts include helping the function of monocytes, neutrophils, and macrophages, and enhancing Natural Killer cells’ activities. Cu also has a role in antimicrobial properties and inflammatory response. It is also important for IL-2 production and response, which is a component of adaptive immune cells. Additionally, Cu has multiple roles in both proliferation and differentiation of T cells and is involved in the production of antibodies. Cu deficiency can even lead to "increased viral virulence"1. Copper has a long history of use in medicine, and has continued to be used for purification of water, including use in hospitals to prevent legionnaires disease. The CDC pre released information on a study completed in March 2020 on the lifespan of COVID-19 on different surfaces which included its lifespan on copper, where it was completely dead within 4 hours. In addition, "Several reports demonstrated that Cu deficiency weakens the human immune response" 2. Given the multiple avenues of impact, it has been suggested that Cu supplementation, within recommended levels, be given to individuals who are low in Cu to help them fight off COVID-19. It is also possible that Cu supplementation, within recommended levels, may help prevent COVID-19 infection, or help individuals who are not low in Cu to fight off COVID-19 infection. However, dosage would have to be carefully managed, as excess levels of Cu can lead to both neurodegenerative and neurodevelopmental diseases.
Nov 2021 DOI 10.14302/issn.2577-2279.ijha-21-3925
Introduction The nose is one of the important component of the face which is considered as the major clue for the ethnic origin. The proportion of the nose is determined on the same principal as that of the skull.The external nose extends the nasal cavities onto the front of the face and positions the nares so that they point downwards. The shape of the nose is pyramidal with its apex anterior in position. The upper angle of the nose between the openings of the orbits is continuous with the forehead. Materials and Methods This study was carried out among residents of Ramnagar Gaupalika-7, Sarlahi,Nepal, one of the core region of Madhesh Nepal dated Jan 2021 to April 2021.The cohort consists of independent adults of age group 17-45 and consenting adults from the metropolis. Ethical approval was sought prior to conducting the study from the supervising ethical committee of the Nobel Medical College Teaching Hospital, Biratnagar, Nepal. Written consents were taken from the subjects for the recruitment in the study. Results The present study involved 100 subjects of equal males and females subjects of age groups 17-45 years from Madheshis community of Nepal. The table 1, table 2, table 3 below shows the values obtained for different parameters for males and females. The mean value of nasal height for male and female is 52.59±1.89 and 50.27±2.16 mm and the nasal width for male and female is 37.64±1.72mm and 35.42±2.04mm and the value of mean nasal index for both the sexes are 71.59±2.31and 70.58±3.04 respectively. The dominant type of the nasal morphology in both the sexes are the mesorrhine type and the leptorrhine type as well. Conclusion The human nose is a dominant feature in facial region which differs in anatomy and morphology among racial groups and of the most characteristic differences during the analysis of ethnic and racial differences. The dominant type of the nasal index is the mesorrhine type in both the male and female of the Madheshis community. Hence the data obtained here will be useful for the differentiation of different ethnic groups of Nepal as well as in the field of forensic science and rhinoplastic surgery.
Oct 2021 DOI 10.14302/issn.2641-5526.jmid-21-3900
In this theoretical discovery of a law of Life, there is MATHEMATICS (Geometry, Bits and Numbers) that UNIFY 3 universes as complementary as ATOMIC MASS, WAVES, and INFORMATION (DNA, RNA and Amino Acids). The discovery of a simple numerical formula for the projection of all the atomic mass of life-sustaining CONHSP bioatoms leads to the emergence of a set of Nested CODES unifying all the biological, genetic and genomic components by unifying them from bioatoms up to 'to whole genomes. In particular, we demonstrate the existence of a digital meta-code common to the three languages of biology that are RNA, DNA and amino acid sequences. Through this meta-code, genomic and proteomic images appear almost analogous and correlated. The analysis of the textures of these images then reveals a binary code as well as an undulatory code whose analysis on the human genome makes it possible to predict the alternating bands constituting the cariotypes of the chromosomes. The application of these codes to perspectives in astrobiology, cancer, and specifically in INFORMATION THEORY with the emergence of binary codes and regions of local stability (voting process), whose fractal nature we demonstrate, is illustrated. PREFACE by Professor Luc Montagnier Addendum by Robert Friedman M.D After the discovery of the DNA double helix structure allowing both the stable storage of genetic information and its transfer through messenger RNA to protein synthesis organelles themselves structured by RNA most abundant in cells, the ribosomal. This wonder of nature exists in ALL living beings from the virus to humans and is based on two codes, the linear sequence of nucleotides and that derived from codons where three nucleotides allow with a certain flexibility - synonymous codons - the choice in the twenty amino acids. But we are missing a third CODE the one governing at multicellular beings from the rotifer to human, the stabilized modulation of gene expression in a nutshell the differentiation of cells from the single cell of the fertilized egg. It is logical to think that this program which begins as soon as fertilization is written in the DNA. We are also prone to associate it with non-coding DNA sequences although they control gene expression. I introduce here the notion developed by Jean-Claude Pérez of mathematical harmony, a higher order present in all living beings and whose existence it finds in genomes, including those of viruses. Thus the natural evolution of variants of the genome of coronavirus Covid 19 tends towards increasingly long Fibonacci series. It remains to determine the Who, the How and the Why of such developments. I will bet with my mathematician colleague that waves and fractals play a role. Luc Montagnier ADDENDUM Jean-claude has given scientists a strong new direction for research. He has identified a unified field of science guided by the Golden Ratio and Fibonacci Sequence. By identifying an overall guiding principle that makes possible fractal-like nesting at all levels of biological manifestation, future researchers can begin with the "whole" instead of the "parts". If we know that complex systems are organized at varying levels by the Golden Ratio and Fibonacci Sequence, we can look for those universal patterns first and then fill in the gaps with small details to complete the picture. It's like having an overall view of a crossword puzzle before beginning to assemble the individual pieces. Without an overarching vision and guiding principle, completing the puzzle is infinitely more difficult. Once scientists and researchers realize and begin using this "SECRET IN HIDDEN IN PLAIN SIGHT," their discoveries will be orders of magnitude more fruitful. Robert Friedman M.D
Jul 2021 DOI 10.14302/issn.2576-6694.jbbs-21-3819
The present study aimed to evaluate the effect of the Trivedi Effect®- Biofield Energy Treated/Blessed Test formulation/item (TI) composed of minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, alpha tocopherol, cyanocobalamin, and cholecalciferol), Panax ginseng extract, CBD isolates, and β-carotene on elasticity of skin, heart, muscle, and neuronal cells in the H9C2 (rat cardiomyocytes), C2C12 (mouse myoblast cells), HaCaT (human keratinocytes), and SH-SY5Y (human neuroblastoma cells) cell line in DMEM medium. The test formulation constituents were divided into two parts; one section was defined as untreated test formulation (UT), while the other portion of test formulation received Biofield Energy Healing/Blessing Treatment (BT) by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The test items were treated with Biofield Energy Healing/Blessing Treatment and divided as Biofield Energy Treated/Blessed (BT) and untreated (UT) test items. MTT data showed that the test formulation in various concentrations was found as safe and nontoxic in the tested concentrations with viability range from 73% to 307%. Young’s modulus (YM) is a measure of cell stiffness, a decrease in YM value indicates increase elasticity of the cells and vice-versa. YM in H9C2 cells were decreased by 9.6% and 66.1% in the BT-DMEM + UT-TI group at 0.1 and 1 µg/mL respectively, as compared with untreated test group. However, C2C21 cells showed increased YM by 443.9% at 1 µg/mL in the UT-DMEM + BT-TI group, while 869.6% increased YM in the BT-DMEM + UT-TI group at 1 µg/mL as compared with untreated test group. However, 314% increased YM was reported in the BT-DMEM + BT-TI group at 1 µg/mL as compared with the untreated test group. However, the value of YM was significantly decreased in the HaCaT cell line by 247.7% (at 1 µg/mL), 225.8% (at 0.1 µg/mL), and 97.9% (at 1 µg/mL) in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. In addition, YM was significantly decreased in the SH-SY5Y cell line by 92.6%, 18.1%, and 26.6% at 1 µg/mL in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. Overall, the results showed the significant decreased YM among the SH-SY5Y, HaCaT, and H9C2 cells, while it was increased in the C2C21 cell line. Thus, the mechanical properties of cells such as cellular function, including shape, motility, differentiation, division, and adhesion to its surrounding extracellular matrix were improved. Overall, it can be useful in many disease progressions with improved cellular elasticity and its associated complications/symptoms.
Mar 2020 DOI 10.14302/issn.2372-6601.jhor-20-3235
Introduction Acute leukaemia are the clonal and malignant proliferation of immature hematopoietic cells (blast), blocked in their differentiation process. There is an interaction between cancer cells and the clotting process. This could be the expression of Tissue Factor (TF) on the surface of tumor cells; or a lesion of the vascular endothelium and platelet activation. The result is an activation of clotting that can lead to disseminated Intravascular Coagulation (DIC). The objective of this study was to assess the risk of DIC occurring in patients with acute leukaemia. Methods This was a cross-sectional study for analytical purposes that took place on 40 frozen samples from the biobank of the haematology laboratory of Teaching Hospital Yopougon for which the diagnosis of acute leukaemia had been taken from myelogram. The myelogram results were accompanied by hemogram data. PTTa, QT, fibrinogen and D-Dimers were performed on these samples. The risk assessment of DIC occurred was determined on the recommendations of the International Society of Thrombosis and Hemostasis (ISTH). Results We noted a female predominance with a Sex Ratio (M / F) of 0.90. The average age of the patients was 38 years (± 23 years) with extremes ranging from 2 to 84 years. ALL represented 20 % of cases against 80 % for AMLs. Hemogram parameters were characterized by severe anaemia (Tx Hb < 6 g / dL) in 52.5 % of cases; hyperleukocytosis > 100.103 / mm3 in 35 % of cases; thrombocytopenia < 25.103 / mm3 in 40 % of case; and significant blood and spinal cord blastosis (> 80 %). The lengthening of the PTTa was observed in 50 % of cases, compared to 40% for the QT. Similarly, hyperfibrinemia was present in 65% of cases. D-Dimers were high in almost all subject (95 % of cases). According to the ISTH criteria, 17.5 % of subjects were at risk of developing a DIC. Conclusion The risk of occurrence of DIC is indeed present during acute leukaemia. The parameters of haemostasis are thus found to be crucial data in the follow-up assessment during the diagnosis of acute leukaemia.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2973
Head and Neck cancer (HNC) is one of the most prevalent and lethal cancer globally. The incidence of tobacco-induced HNC is gradually increasing in low and middle income countries. Among the various causative factors associated with HNCs, tobacco and alcohol play synergistic effect and are frequently associated with the risk of HNC. Tobacco-induced HNCs show distinct genetic and epigenetic alterations leading to different clinical outcomes in comparison to HPV-infected HNCs. Tobacco-induced HNCs are often associated with tumor aggressiveness, poor prognosis and low or nil prevalence of HPV infection. Apart from carcinogenic effects of these causative factors (use of tobacco products, alcohol intake and HPV or EBV infections), recent studies show that exposure to these factors alter/disrupt the regulation of non-coding RNAs including the long non-coding RNAs (lncRNAs). Altered lncRNA regulation is brought about by signalling networks that regulate cellular differentiation, apoptosis, angiogenesis and inflammatory pathways which play key functions in the genesis of different cancers including HNCs. There are numbers of studies supporting the emerging role of lncRNAs in development of HNC; however, reports connecting lncRNAs expression and addiction habits in HNC are still preliminary and sparse. Therefore, identification and characterization of lncRNAs that are differentially expressed upon exposure to risk-factors can serve as unique therapeutic targets and potential biomarker(s) for effective treatment of HNC subtypes. In this short review, we briefly reviewed the emerging role of lncRNAs in tobacco and alcohol induced HNCs.
Oct 2018 DOI 10.14302/issn.2577-2279.ijha-18-2407
Oligodendrocytes are specialized glial cell in central nervous system (CNS) responsible for the formation of myelin sheath around the axon. Oligodendrocyte proliferation and differentiation is regulated by Wnt signaling pathway, at various stages. However, different study groups have described controversial conclusions about the effect of Wnt on oligodendrocytes precursor cells (OPCs) development. Initially it has been proposed that Wnt pathway negatively regulates the OPCs proliferation and differentiation but recently some studies have described that Wnt promotes the differentiation of OPCs. After carefully reviewing the literature, we believe that Wnt play multiple roles in OPCs differentiation and its function is time (stage) and dose sensitive. Low to moderate activation of Wnt promotes OPC development, while too much or too low is inhibitory. Current evidences also suggested that in early developmental stages, Wnt inhibits the OPCs formation from neural progenitors and differentiation into immature oligodendrocytes. But in late stages Wnt plays promoting role in differentiation and maturation of oligodendrocytes. This review summarized the updated information regarding the critical role of Wnt signaling cascade in proliferation and differentiation of OPCs.
Sep 2018
MicroRNAs are short sequences of non-coding RNAs crucial in regulation of cell development, proliferation and differentiation. Some of them showed to be related with the expression of osteogenic genes. Aim of the present review was to evaluate the biological effects of titanium implant surfaces activated with miRNAs or antimiRNAs. A bibliographical electronic research was carried out on PubMed/Medline. Articles investigating the influences of miRNA functionalized surfaces on human or animal cells were included. Reports were excluded if investigating surfaces modified with molecules different from miRNAs, if miRNAs were not loaded to titanium surfaces. Five articles met the inclusion criteria. Surfaces functionalized with miRNAs showed to up-regulate the expression of osteogenic genes like RUNX2, OPN, OCN, BMP, OSX, ALP, COL1 and COL3. Investigated surfaces additionally showed more bone-like mineralized tissues, bone lacunae, osteocytes and new blood vessels. MiRNAs loaded to titanium implant surfaces stimulate the expression of genes related to osteoblasts differentiation, osteogenesis, osseointegration and reparation of mineralized tissues. Vectors used to link titanium surfaces and miRNAs did not show cytotoxicity or interference with cells’ viability.
Aug 2018 DOI 10.14302/issn.2572-3030.jcgb-18-2183
This paper reviews the state of cancer research in the post-mutation era. It presents cancer as a highly complex disease viewed differently by scientists from various research fields. Histopathologists considered cancer as a disease of cell differentiation, cancer cell biologists overestimated the causal role of accumulated DNA mutations. More recently molecular biologists have focused on driver genes and driver mutations, regulatory gene networks and deregulation of the genomic balance between unicellular and multicellular gene sets (UG/MG balance). From a developmental biological standpoint, there is a clear analogy between the reproductive life cycles of cancer and protists. The key player of both analogous life cycles is the polyploid cyst, the atavistic cyst-like structure aCLS (PGCC). In the analogy to protists, we assume that the first aCLS initiating cancer originates from a mitoticly blocked cell (cell of origin of cancer, protoprecursor) that escapes death entering an atavistic reproductive process of polyploidisation and depolyploidisation; it forms the atavistic cyst-like structure aCLS and numerous daughter cells (microcells). The microcell progeny develops a multi-lined cell lineage containing stem cells as well as somatic and reproductive cells and clones. Subsequent aCLSs are formed sequentially by committed daughter cells or occasionally by stressed somatic cells. Accordingly, cancer initiation occurs by genomic changes leading to the amitotic cell state and reactivation of an atavistic life cycle. In humans, atavistic life cycles and hyperpolyploidisation (n >16) are mostly repressed by stable gene regulatory networks – but not in cancer. The permanent UG/MG gene conflict and robust ancient surveillance mechanisms trigger a cascade of molecular lesions leading to genomic heterogeneity and aberrant cancer cell states.
Jun 2018 DOI 10.14302/issn.2641-9467.jgrc-18-2041
The present study aims at integrating the characterization studies conducted on the Cuban germplasm collection of Xanthosoma sagittifolium (Araceae) preserved in the Research Institute of Tropical Roots and Tubers Crops (INIVIT). Differentiation of accessions was done by combining qualitative and quantitative descriptors to clarify the relationships between six well-defined groups. The results may be used to establish a core collection for improved management of Xanthosoma spp. germplasm.
Dec 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1869
Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).
Dec 2017 DOI 10.14302/issn.2640-6403.jtrr-17-1818
If a wound progressively heals or the healing process is impaired is basically influenced by the surrounding milieu. This is reflected by the wound fluid. Its specific composition triggers the migration, proliferation and differentiation of dermal and epidermal cells which so far was not sufficiently examined in 2D cell culture models. The influence of the different wound entities was analyzed on a newly implemented three dimensional in-vitro model, which improved the transferability to the in-vivo situation. The influence of pooled wound fluids from patients suffering from acute or chronic wounds were investigated within a time period of 10 days after wound application. Histological and immunohistochemical analyses were performed addressing the impact of AWF and CWF on regeneration, such as cell proliferation, fibroblast activity and cell migration. AWF slightly stimulated fibroblast migration while CWF inhibited their activation and migration. The CXCR4- immunopositive population was continuously decreased compared to the control and AWF treatment. The expression of FAP was enhanced under AWF and medium. In keratinocytes CWF massively stimulated cell proliferation initiating on day six after injury. The presence of 10% CWF inhibited fibroblast activation and migration and induced the degradation of the collagen matrix. Keratinocytes were stimulated to proliferate, resulting in healing inhibiting hyperplasia. Transferred to human wounds, no effective wound closure would be achieved because of the de-regulation of pro-proliferative and migration-stimulating factors and a degraded extracellular matrix. This newly implemented 3D study model represents a novel appropriate in-vitro system for studying healing mechanisms and potential therapeutic applications.
Aug 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1662
Immunization of cattle with the bacillus Calmette-Guérin (BCG) vaccine, especially neonates, induces protection against Mycobacterium bovis (M. bovis) and has been proposed as a strategy for bovine tuberculosis (bTB) control. Therefore, the aim of this study was to evaluate the immune response induced under field conditions in neonatal calves vaccinated with BCG Phipps, a strain that has rarely been evaluated in the bovine population, using interferon (IFN)-γ and tuberculin tests, flow cytometry and enzyme-linked immunosorbent assay. Two groups (vaccinated and control) of 5 calves were monitored for 12 weeks, and increases in the in vitro IFN-γ production, the percentage of cluster of differentiation (CD)8+ T cells and the activation levels of CD4+ and CD8+ T cells were observed 3 to 4 weeks post-vaccination. Bovine purified protein derivative-specific IFN-γ production was increased about 4.8- and 5.5-fold in vaccinated animals compared to non-vaccinated animals 3 and 4 weeks post-vaccination respectively. CD8+ T cells of the vaccinated group were increased 1.6-, 1.5- and 1.6-fold at weeks 2, 3 and 4 respectively. Levels of activation were 1.7- and 1.9-fold higher for CD4+ T cells and 2.3- and 1.8-fold higher for CD8+ T cells in the vaccinated group at weeks 3 and 4 respectively in response to M. bovis antigens. However, no animals (vaccinated or control) showed positive results for the single intradermal comparative tuberculin test (SICTT). Therefore, our results indicate that vaccination with M. bovis BCG Phipps strain stimulated peripheral blood T cell activity and induced a cell-mediated immune response. In addition, vaccination did not interfere with the SICTT, as previously reported, which indicates that this vaccine could be successfully applied in bTB control campaigns.
Aug 2017 DOI 10.14302/issn.2576-2818.jfb-14-553
All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a “wave” of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive. During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.
Jun 2017 DOI 10.14302/issn.2329-9487.jhc-17-1536
Over the last few decades, many research works highlighted the role of miRNAs on cardiac diseases. Ischaemic heart disease (IHD) or coronary heart disease is a condition that is mainly caused by atherosclerosis. It has been established that microribonucleic acids regulate many factors that are involved in the development and pathophysiology of IHD. As a result, there are great potential opportunities for miRNAs to be used as a biomarker for disease differentiation, as well as novel drug targets or therapeutics for the treatment and also as a diagnostic approach. As it is now evident that miRNAs play critical roles in the disease mechanisms, this review article tried to focus on the pathway, in which; the miRNAs stimulate the IHD to develop. By understanding the mechanisms, it will be possible to present a complete strategy of IHD treatment and also solving all the impediments that are highlighted in this article. Still, there are a number of limitations and obstacles on the way of developing a proper therapeutic approach that can be approved and well accepted. This review is mainly dependent on the potential of miRNAs as a promising arena on the field of cardiac treatment and the possible obstacles that are needed to be explored and overcome.
Jun 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1481
Background: Studies have unveiled lower levels of serum vitamin D in autoimmune diseases and the role of vitamin D in inhibition of helper T cells proliferation, stimulation of regulatory T cells, diminishing of B-lymphocyte differentiation and inhibition of immunoglobulin secretion has been discussed in the literature. Oral lichen planus (OLP) is an autoimmune mucocutaneous disorder in which cell mediated immunity plays an important part and so it may also be related to serum vitamin D levels. Aim: To estimate serum vitamin D in oral lichen planus patients of North India, compare it to the controls and to evaluate various factors influencing vitamin D level in OLP cases such as sun exposure, gender, psychosocial factors, meteorological influences, religion and diet. Methods and Material: Venous blood samples of 102 clinically diagnosed oral lichen planus patients and 102 age and sex matched controls were obtained for the study and serum vitamin D levels were estimated using Vitek Immunodiagnostic Assay System, an automated bench-top immuno-analyzer, based on the Enzyme Linked Fluorescent Assay. The data was analyzed using chi-squared test and t-test. Results: Mean vitamin D in OLP cases and controls was 20.40 ng/ml and 32.67 ng/ml respectively. Vitamin D3 deficiency was more in OLP cases (70.6%) as compared to controls (34.3%) and insufficiency was more in controls (35.3%) as compared to OLP cases (16.7%). These differences were statistically significant. Conclusion: Although vitamin D deficiency was found more in OLP cases pointing towards the possible co-relation of vitamin D and OLP, yet insufficiency was seen more commonly in controls which revealed that this important vitamin was lacking in North Indian population.
Jan 2017 DOI 10.14302/issn.2574-4372.jesr-16-1327
Stem cell-based regenerative therapy can be considered an innovative approach for curing dental caries. Pulp stem cells from human exfoliated deciduous teeth (SHEDs) represent a source of committed cells for generating odontoblasts in vitro; however, SHEDs are not easy to obtain and are limited in quantity. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered to be adult stem cells that can be easily obtained in large numbers. Here, SHEDs and UC-MSCs were conditioned in custom-made serum-free culture media in order to induce differentiation towards odontoblasts. SHEDs and UC-MSCs were expanded in vitro and differentiated into odontoblasts for 21 days using a medium containing transforming growth factor-β (TGF-b3), hepatocyte growth factor (HGF) and growth differentiation factor 5 (GDF5). The ability to induce odontoblast differentiation with a straightforward clinical protocol in compliance with good manufactoring practice (GMP), which avoids animal reagents, and uses unrelated stem cells of unrestricted availability, may be a first step towards a new innovative approach for dentin regeneration.
Jul 2016 DOI 10.14302/issn.2574-4372.jesr-16-1055
Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.