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Chondrogenesis is a multistep process, in which cartilage progenitor cells generate a tissue with distinct structural and functional properties. Although several approaches to cartilage regeneration rely on the differentiation of implanted progenitor cells, the temporal transcriptomic landscape of in vitro chondrogenesis in different models has not been reported. Using RNA sequencing, we examined differences in gene expression patterns during cartilage formation in micromass cultures of embryonic limb bud-derived progenitors. Principal component and trajectory analyses revealed a progressively different and distinct transcriptome during chondrogenesis. Differentially expressed genes (DEGs), based on pairwise comparisons of samples from consecutive days were classified into clusters and analysed. We confirmed the involvement of the top DEGs in chondrogenic differentiation using pathway analysis and identified several chondrogenesis-associated transcription factors and collagen subtypes that were not previously linked to cartilage formation. Transient gene silencing of ATOH8 or EBF1 on day 0 attenuated chondrogenesis by deregulating the expression of key osteochondrogenic marker genes in micromass cultures. These results provide detailed insight into the molecular mechanism of chondrogenesis in primary micromass cultures and present a comprehensive dataset of the temporal transcriptomic landscape of chondrogenesis, which may serve as a platform for new molecular approaches in cartilage tissue engineering.
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Condrogênese , Transcriptoma , Condrogênese/genética , Cartilagem/metabolismo , Diferenciação Celular/genética , Células-Tronco/metabolismo , Células Cultivadas , Condrócitos/metabolismoRESUMO
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease affecting different organ systems. This study aimed to determine the concentrations of 30 different human cytokines, chemokines, and growth factors in human plasma to understand the role of these markers in the pathogenicity of SLE using Luminex Multiple Analyte Profiling (xMAP) technology. Plasma samples were obtained from patients with SLE (n = 28), osteoarthritis (OA) (n = 9), and healthy individuals (n = 12) were obtained. High levels of TNF, IL-6, IFN-γ, INF-α, IL-4, IL-5, IL-13, IL-8, IP-10, MIG, MCP-1, MIP-1ß, GM-CSF, G-CSF, EGF, VEGF, IL-12, IL-1RA, and IL-10 was detected in SLE patients compared with the OA and healthy control groups. xMAP analysis has been used to address the differential regulation of clinical heterogeneity and immunological phenotypes in SLE patients. In addition, complete disease phenotyping information along with cytokine immune profiles would be useful for developing personalized treatments for patients with SLE.
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Citocinas , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Projetos Piloto , QuimiocinasRESUMO
Mast cells (MCs) are tissue-resident innate immune cells that express the high-affinity receptor for immunoglobulin E and are responsible for host defense and an array of diseases related to immune system. We aimed in this study to characterize the pathways and gene signatures of human cord blood-derived MCs (hCBMCs) in comparison to cells originating from CD34- progenitors using next-generation knowledge discovery methods. CD34+ cells were isolated from human umbilical cord blood using magnetic activated cell sorting and differentiated into MCs with rhIL-6 and rhSCF supplementation for 6-8 weeks. The purity of hCBMCs was analyzed by flow cytometry exhibiting the surface markers CD117+CD34-CD45-CD23-FcεR1αdim. Total RNA from hCBMCs and CD34- cells were isolated and hybridized using microarray. Differentially expressed genes were analyzed using iPathway Guide and Pre-Ranked Gene Set Enrichment Analysis. Next-generation knowledge discovery platforms revealed MC-specific gene signatures and molecular pathways enriched in hCBMCs and pertain the immunological response repertoire.
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Sangue Fetal , Mastócitos , Humanos , Descoberta do Conhecimento , Antígenos CD34/genética , Diferenciação Celular/genéticaRESUMO
Objectives: Accurately identifying the cellular, biomolecular, and toxicological functions of anticancer drugs help to decipher the potential risk of genotoxicity and other side effects. Here, we examined bleomycin for cellular, molecular and toxicological mechanisms using next-generation knowledge discovery (NGKD) tools. Methods: This study was conducted at the Faculty of Applied Medical Sciences, King Abdulaziz University (KAU), Jeddah, Saudi Arabia in October 2022. We first analyzed the raw Toxicogenomic and DNA damage-inducing (TGx-DDI) gene expression data from Gene Expression Omnibus (GEO) (GSE196373) of TK6 cells treated with 10 µM bleomycin and TK6 cells treated with DMSO for four hours using the GEO2R tool based on the Linear Models for Microarray Analysis (limma) R packages to derive the differentially expressed genes (DEGs). Then, iPathwayGuide was used to determine differentially regulated signaling pathways, biological processes, cellular, molecular functions and upstream regulators (genes and miRNAs). Results: Bleomycin differently regulates the p53 pathway, transcriptional dysregulation in cancer, FOXO pathway, viral carcinogenesis, and cancer pathways. The biological processes such as p53 class mediator signaling, intrinsic apoptotic signaling, DNA damage response, and DNA damage-induced intrinsic apoptotic signaling and molecular functions like ubiquitin protein transferase and p53 binding were differentially regulated by bleomycin. iPathwayGuide analysis showed that the p53 and its regulatory gene and microRNA networks induced by bleomycin. Conclusion: Analysis of TGx-DDI data of bleomycin using NGKD tools provided information about toxicogenomics and other mechanisms. Integration of all "omics" based approaches is crucial for the development of translatable biomarkers for evaluating anticancer drugs for safety and efficacy.
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Background & Objectives: Accurate identification of molecular and toxicological functions of potential drug candidates is crucial for drug discovery and development. This may aid in the evaluation of the risks of genotoxicity and carcinogenesis. In addition, in silico characterization of existing and new drugs might offer clues for future investigations and aid in the development of anticancer treatments. Using next-generation knowledge discovery (NGKD) methodology, we endeavored to establish a risk assessment of anticancer drugs for their molecular mechanism(s) and genotoxicity. Methods: This study was performed at the Faculty of Applied Medical Sciences, King Abdulaziz University (KAU), Jeddah, Saudi Arabia, in November 2022. Using innovative in silico model systems, we assessed the molecular mechanism of action and toxicity of around 20 distinct substances such as Deguelin, Etoposide, Camptothecin, Cytarabine (Ara-C), Cisplatin, Hydroxyurea, Trichostain A, Antimycin, Colchicine, 2-deoxyglucose, Tunicamycin, Thapsigargin, Vinblastin, Docetaxel, Oxaliplatin, Methotrexate, 5-flurouracil, Bleomycin, Taxol (Paclitaxel), and Apicidin. Using the Ingenuity Pathway Analysis (IPA) knowledge base, the number of targets for each compound was determined in silico. Subsequently, they were examined using Fisher's exact test and Benjamini Hochberg Multiple Testing Correction (P<0.05) and submitted to core analysis with IPA to decode the biological and toxicological activities differently controlled by these drugs. In addition, a multiple comparison module in IPA was used to compare the core analyses of each molecule. In addition, we obtained the top 100 protein targets of Etoposide, Camptothecin, and Ara-C using SwissTargetPrediction, as well as the key pathways and gene ontologies affected by these drugs and disease associations using the WebGestalt tool. Results: We identified distinct toxicological signatures and canonical signaling pathways in tumor cell lines regulated by these 20 anticancer drugs. These signaling pathways included cell death and apoptosis in addition to molecular processes, p53 signaling, and aryl hydrocarbon receptor signaling. The TP53 signaling pathway is utilized by these agents to effectively trigger cell death and apoptosis, and p53 functions as a master regulator in a variety of cellular stress responses, including genotoxic stress. Conclusion: Our research has laid the groundwork for the discovery of additional biomarkers that assess both the safety and effectiveness of treatment. Our mechanism based "NGKD" tools have more relevance for the identification of safer therapies and has the potential to lead to the rational screening of drug candidates targeting specific molecular networks and canonical pathways implicated in cancer and genotoxicity. In addition, the combination of protein, microRNA and metabolome profiles may be essential for the development of translatable biomarkers for the safety and efficacy of pharmacotherapeutic agents.Our research has laid the groundwork for the discovery of additional biomarkers that assess both the safety and the effectiveness of a treatment.
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Assisted reproductive technologies (ART) are considered as one of the primary management options to address severe male factor infertility. The purpose of this study was to identify the research trends in the field of male infertility and ART over the past 20 years (2000-2019) by analysing scientometric data (the number of publications per year, authors, author affiliations, journals, countries, type of documents, subject area and number of citations) retrieved using the Scopus database. We used VOS viewer software to generate a network map on international collaborations as well as a heat map of the top scientists in this field. Our results revealed a total of 2,148 publications during this period with Cleveland Clinic Foundation contributing the most (n = 69). The current scientometric analysis showed that the research trend on ART has been stable over the past two decades. Further in-depth analysis revealed that density gradient centrifugation (46%) and intracytoplasmic sperm injection (59.2%) are the most reported techniques for sperm separation and ART, respectively. Additionally, azoospermia was the most studied clinical scenario (60.6%), with majority of articles reporting pregnancy rate (47.25%) as the primary reproductive outcome for ART. This study provides insight into the current focus of research in the area of male infertility and ART as well as the areas that require further research in future.
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Infertilidade Masculina , Técnicas de Reprodução Assistida , Feminino , Humanos , Infertilidade Masculina/terapia , Masculino , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas , EspermatozoidesRESUMO
In 2020, the COVID-19 pandemic led to the suspension of the annual Summer Internship at the American Center for Reproductive Medicine (ACRM). To transit it into an online format, an inaugural 6-week 2020 ACRM Online Mentorship Program was developed focusing on five core pillars of andrology research: scientific writing, scientific methodology, plagiarism understanding, soft skills development and mentee basic andrology knowledge. This study aims to determine mentee developmental outcomes based on student surveys and discuss these within the context of the relevant teaching and learning methodology. The mentorship was structured around scientific writing projects established by the team using a student-centred approach, with one-on-one expert mentorship through weekly formative assessments. Furthermore, weekly online meetings were conducted, including expert lectures, formative assessments and social engagement. Data were collected through final assessments and mentee surveys on mentorship outcomes. Results show that mentees (n = 28) reported a significant (p < .0001) improvement in all criteria related to the five core pillars. These results illustrate that the aims of the online mentorship program were achieved through a unique and adaptive online educational model and that our model has demonstrated its effectiveness as an innovative structured educational experience through the COVID-19 crisis.
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Andrologia/educação , Educação a Distância/organização & administração , Escrita Médica , Modelos Educacionais , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Avaliação Educacional/estatística & dados numéricos , Feminino , Humanos , Masculino , Mentores , Pandemias/prevenção & controle , Plágio , Estudantes/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Comunicação por Videoconferência/organização & administraçãoRESUMO
BACKGROUND: This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999-2018) using a scientometric approach. METHODS: A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology. RESULTS: A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933). CONCLUSIONS: Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes.
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Pesquisa Biomédica/tendências , Fragmentação do DNA , Infertilidade Masculina/genética , Espermatozoides/química , Astenozoospermia/genética , Dano ao DNA , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , National Institutes of Health (U.S.) , Editoração/tendências , Técnicas de Reprodução Assistida , Estados Unidos , Varicocele/genéticaRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer. METHODS: Thirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles. RESULTS: DEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1ß,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D). CONCLUSIONS: ADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC.
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Antineoplásicos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Phoeniceae/química , Extratos Vegetais , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/análise , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Citocinas/sangue , Dietilnitrosamina/toxicidade , Frutas/química , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos WistarRESUMO
Poor compliance with conventional asthma medications remains a major problem in achieving asthma control. Nigella sativa oil (NSO) is used traditionally for many inflammatory conditions such as asthma. We aimed to investigate the benefits of NSO supplementation on clinical and inflammatory parameters of asthma. NSO capsules 500 mg twice daily for 4 weeks were used as a supplementary treatment in a randomized, double-blind, placebo-controlled trial in asthmatics (clinicaltrials.gov: NCT02407262). The primary outcome was Asthma Control Test score. The secondary outcomes were pulmonary function test, blood eosinophils and total serum Immunoglobulin E. Between 1 June and 30 December 2015, 80 asthmatics were enrolled, with 40 patients in each treatment and placebo groups. After 4 weeks, ten patients had withdrawn from each group. Compared with placebo, NSO group showed a significant improvement in mean Asthma Control Test score 21.1 (standard deviation = 2.6) versus 19.6 (standard deviation = 3.7) (p = 0.044) and a significant reduction in blood eosinophils by -50 (-155 to -1) versus 15 (-60 to 87) cells/µL (p = 0.013). NSO improved forced expiratory volume in 1 second as percentage of predicted value by 4 (-1.25 to 8.75) versus 1 (-2 to 5) but non-significant (p = 0.170). This randomized, double-blind, placebo-controlled trial demonstrated that NSO supplementation improves asthma control with a trend in pulmonary function improvement. This was associated with a remarkable normalization of blood eosinophlia. Future studies should follow asthmatics for longer periods in a multicentre trial. Copyright © 2017 John Wiley & Sons, Ltd.
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Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Nigella sativa/química , Extratos Vegetais/administração & dosagem , Adulto , Asma/sangue , Asma/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Terapia Combinada , Progressão da Doença , Método Duplo-Cego , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fitoterapia/métodos , Placebos , Testes de Função Respiratória , Resultado do TratamentoRESUMO
The Third International Genomic Medicine Conference (3rd IGMC) was organised by the Centre of Excellence in Genomic Medicine Research (CEGMR) at the King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia (KSA). This conference is a continuation of a series of meetings, which began with the first International Genomic Medicine Conference (1st IGMC, 2011) followed by the second International Genomic Medicine Conference (2nd IGMC, 2013). The 3rd IGMC meeting presented as a timely opportunity to bring scientists from across the world to gather, discuss, and exchange recent advances in the field of genomics and genetics in general as well as practical information on using these new technologies in different basic and clinical applications. The meeting undoubtedly inspired young male and female Saudi researchers, who attended the conference in large numbers, as evidenced by the oversubscribed oral and poster presentations. The conference also witnessed the launch of the first content for npj Genomic Medicine, a high quality new journal was established in partnership by CEGMR with Springer Nature and published as part of the Nature Partner Journal series. Here, we present a brief summary report of the 2-day meeting including highlights from the oral presentations, poster presentations, workshops, poster prize-winners and comments from the distinguished scientists.
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Genômica , Medicina , Biologia Computacional/métodos , Predisposição Genética para Doença , Genômica/métodos , Humanos , Medicina/métodosRESUMO
Colorectal cancer (CRC) is the second most common cancer in the world. In Saudi Arabia, CRC is the most common cancer in males and the third most common in females, and its incidence rate is rising as the country continues to develop. However, the country does not have a national CRC screening program for CRC. This review aims to review recent studies that have attempted to address and rectify this issue and discern the most notable and prevalent barriers. Despite these efforts, guidelines are still lacking. Two prospective studies have been conducted in recent years, one of which was a national pilot screening program conducted by the Ministry of Health (MOH). While both had a similar number of participants, the colonoscopy rate for patients with a positive fecal immunochemical test (FIT) in the MOH program was only 20% compared to 75.8% in the Al-Kharj program. Awareness of the Saudi population regarding CRC and its screening appears to be insufficient. The most common barriers to patients' willingness to undergo screening were embarrassment, fear, and pain. Barriers to physicians are mostly related to factors outside their hands, such as lack of equipment and time. We conclude that efforts should be made to establish a national screening program and improve awareness of the population and physicians.
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Cardiovascular disease (CVD) is one of the main causes of death in Saudi Arabia. Cardiac remodeling plays a critical role in the pathophysiology of heart failure. Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.
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Humans suffer from various diseases that require more specific drugs to target them. Among the different potent agents, ß-lactamases serve as good antibacterial agents; however, ß-lactamases are resistant to such antibiotics. The present study was designed to prepare efficient ß-lactamase inhibitor amides (12-15) from inexpensive, easily accessible, and bioactive precursors; Morita Baylis Hillman (MBH) adducts (5-8). The adducts (5-8) were primarily prepared by treating their respective aldehydes with the corresponding acrylate in the presence of an organic Lewis base at ambient temperature. The compounds were characterized using mass spectrometry, FTIR and NMR spectroscopy. Furthermore, in silico studies (using AutoDock Tools and AutoDock Vina programs) on the adduct and corresponding amide product revealed that all MBH adducts (5-8) and their product amides (12-15) are significant inhibitors of ß-lactamase. Additionally, among the MBH adducts, adduct 7 showed the highest binding affinity with ß-lactamase, whereas amide 15 was identified as a highly potent antibacterial based on its docking score (-8.6). In addition, the absorption, distribution, metabolism, and excretion (ADME) test of the synthesized compounds demonstrated that all compounds showed drug-likeness properties.
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Mast cells are multifaceted cells localized in tissues and possess various surface receptors that allow them to respond to inner and external threat signals. Interleukin-33 (IL-33) is a cytokine released by structural cells in response to parasitic infections, mechanical damage, and cell death. IL-33 can activate mast cells, causing them to release an array of mediators. This study aimed to identify the different cytokines released by human cord blood-derived mast cells (hCBMCs) in response to acute and prolonged stimulation with IL-33. For this purpose, a hCBMC model was established and stimulated with 10 ng and 20 ng of recombinant human IL-33 (rhIL-33) for 6 h and 24 h. Total RNA was hybridized using a high-density oligonucleotide microarray. A multiplex assay was performed to assess the released cytokines. Acute exposure to rhIL-33 increased the expression of IL-1α, IL-1ß, IL-6, and IL-13, whereas prolonged exposure increased the expression of IL-5 and IL-10, and cytokines were detected in the culture supernatant. WebGestalt analysis revealed that rhIL-33 induces pathways and biological processes related to the immune system and the acute inflammatory response. This study demonstrates that rhIL-33 can activate hCBMCs to release pro- and anti-inflammatory cytokines, eliciting distinct acute and prolonged responses unique to hCBMCs.
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Congenital heart disease (CHD) encompasses a diverse range of structural and functional anomalies that affect the heart and the major blood vessels. Epidemiological studies have documented a global increase in CHD prevalence, which can be attributed to advancements in diagnostic technologies. Extensive research has identified a plethora of CHD-related genes, providing insights into the biochemical pathways and molecular mechanisms underlying this pathological state. In this review, we discuss the advantages and challenges of various In vitro and in vivo CHD models, including primates, canines, Xenopus frogs, rabbits, chicks, mice, Drosophila, zebrafish, and induced pluripotent stem cells (iPSCs). Primates are closely related to humans but are rare and expensive. Canine models are costly but structurally comparable to humans. Xenopus frogs are advantageous because of their generation of many embryos, ease of genetic modification, and cardiac similarity. Rabbits mimic human physiology but are challenging to genetically control. Chicks are inexpensive and simple to handle; however, cardiac events can vary among humans. Mice differ physiologically, while being evolutionarily close and well-resourced. Drosophila has genes similar to those of humans but different heart structures. Zebrafish have several advantages, including high gene conservation in humans and physiological cardiac similarities but limitations in cross-reactivity with mammalian antibodies, gene duplication, and limited embryonic stem cells for reverse genetic methods. iPSCs have the potential for gene editing, but face challenges in terms of 2D structure and genomic stability. CRISPR-Cas9 allows for genetic correction but requires high technical skills and resources. These models have provided valuable knowledge regarding cardiac development, disease simulation, and the verification of genetic factors. This review highlights the distinct features of various models with respect to their biological characteristics, vulnerability to developing specific heart diseases, approaches employed to induce particular conditions, and the comparability of these species to humans. Therefore, the selection of appropriate models is based on research objectives, ultimately leading to an enhanced comprehension of disease pathology and therapy.
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Allergy and anaphylaxis are inflammatory disorders caused by immune reactions mainly induced by immunoglobulin-E that signal through the high-affinity FcεRI receptor to release the inflammatory mediators from innate immune cells. The FcεRI/mast cell axis is potently involved in triggering various intracellular signaling molecules to induce calcium release from the internal stores, induction of transcription factors such as NF-kB, secretion of various cytokines as well as lipid mediators, and degranulation, resulting in the induction of allergy and anaphylaxis. In this review, we discuss various cellular and molecular mechanisms triggered through FcεRI/mast cell axis in allergy and anaphylaxis with a special emphasis on the functional genomics paradigm.
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Anafilaxia/genética , Genômica , Mastócitos/imunologia , Receptores de IgE/genética , Anafilaxia/imunologia , Animais , Basófilos/imunologia , Degranulação Celular/imunologia , Regulação da Expressão Gênica/imunologia , Histamina/imunologia , Humanos , Imunoglobulina E/genética , Imunoglobulina E/imunologia , Camundongos , Ratos , Receptores de IgE/imunologiaRESUMO
Oral Squamous cell Cancers (OSCC) is strongly associated with tobacco consumption. We here in present a case study of a OSCC patient who refused standard oncological care (SOC), to highlight the importance of integrating palliative care (PC) for improved patient outcomes. A 61 years male patient, with history of chewing tobacco for more than 20 years and diagnosed to have OSCC for 1.5 years presented with severe anaemia and a cauliflower-like growth (12 x 10 cm) in the left oral cavity and cheek with greenish-yellow discharge. Pus culture was positive for K. pneumoniae and P. aeruginosa. Patient is also a known hypertensive for 15 years and a diabetic for 7 years on allopathic treatment. However, the patient refused SOC for oral cancer and relied on siddha treatment. Packed cell transfusions were given to correct anaemia and the blood glucose levels was kept under control. Frequent wound debridement, oral care, antibiotics, balanced-diet and hydration improved wound-bed granulation. Patient and family members were counselled and explained in detail on the need for SOC by sharing previous OSCC patients' care and outcomes at our centre. Patient gained trust and courage and agreed for chemotherapy, which reduced the disease burden and improved the quality of life (QoL) considerably. Therefore, PC integration at an early stage of treatment is imperative as it reduced (i) the burden of secondary infection, (ii) pain and distress, and (iii) improved the QoL.
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Introduction: Clusterin is a moonlighting protein that has many functions. It is a multifunctional holdase chaperone glycoprotein that is present intracellularly and extracellularly in almost all bodily fluids. Clusterin is involved in lipid transport, cell differentiation, regulation of apoptosis, and clearance of cellular debris, and plays a protective role in ensuring cellular survival. However, the possible involvement of clusterin in arthritic disease remains unclear. Given the significant potential of clusterin as a biomarker of osteoarthritis (OA), a more detailed analysis of its complex network in an inflammatory environment, specifically in the context of OA, is required. Based on the molecular network of clusterin, this study aimed to identify interacting partners that could be developed into biomarker panels for OA. Methods: The STRING database and Cytoscape were used to map and visualize the clusterin connectome. The Qiagen Ingenuity Pathway Analysis (IPA) software was used to analyze and study clusterin associated signaling networks in OA. We also analyzed transcription factors known to modulate clusterin expression, which may be altered in OA. Results: The top hits in the clusterin network were intracellular chaperones, aggregate-forming proteins, apoptosis regulators and complement proteins. Using a text-mining approach in Cytoscape, we identified additional interacting partners, including serum proteins, apolipoproteins, and heat shock proteins. Discussion: Based on known interactions with proteins, we predicted potential novel components of the clusterin connectome in OA, including selenoprotein R, semaphorins, and meprins, which may be important for designing new prognostic or diagnostic biomarker panels.
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Conectoma , Osteoartrite , Humanos , Clusterina , Condrócitos/metabolismo , Biomarcadores , BiologiaRESUMO
Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disorder that typically affects young male adults in their second and third decades of life. It usually manifests as painless, subacute, progressive, bilateral vision loss, with more than 90% of affected individuals losing their vision before age 50. Compared with other diseases that cause optic neuritis (multiple sclerosis or neuromyelitis optica spectrum disorders), LHON has worsening visual function in the first 6-12 months of disease progression, is predominantly male, the optic nerve is affected bilaterally from onset, there is no gadolinium enhancement on MRI, no response to disease-modifying therapy, and there is a family history of mutation in mitochondrial DNA. In this article, we describe an interesting and challenging case of LHON due to a homoplasmic variant in the MT -CO3 gene that was initially misdiagnosed as a monophasic demyelinating disorder (clinically isolated syndrome vs acute disseminated encephalomyelitis vs neuromyelitis optica spectrum disorders).