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1.
Adv Protein Chem Struct Biol ; 141: 67-86, 2024.
Article in English | MEDLINE | ID: mdl-38960487

ABSTRACT

Metalloproteins play a crucial role in regulating different aspects of the immune system in humans. They have various functions in immunity, including recognizing and presenting antigens, aiding in the movement and effectiveness of immune cells, and facilitating interactions between the host and pathogens. Understanding how these proteins work can help us develop new methods to control the immune response in different diseases. Metalloproteins contain metal ions in their structure, which allows them to perform these diverse functions. They encompass a wide range of enzymes, signaling molecules, and structural proteins that utilize metal ions as cofactors for their activities. Examples of metalloproteins include superoxide dismutase, catalase, and metalloproteases, which regulate oxidative stress, inflammation, and tissue remodelling processes associated with immune activation. By studying their functions and the effects of their dysfunction, researchers can develop strategies to improve immune function and combat various diseases. This review explores the diverse functions of metalloproteins in immune processes, highlighting their significance in both health and disease.


Subject(s)
Metalloproteins , Humans , Metalloproteins/chemistry , Metalloproteins/immunology , Metalloproteins/metabolism , Animals
2.
Environ Sci Pollut Res Int ; 31(27): 39406-39420, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38816633

ABSTRACT

Numerous research studies have found that a double-pass solar air heater (DPSAH) performs better than a single-pass solar air heater (SAH). This suggested study aims to evaluate the performance of a DPSAH setup in Southern Tamil Nadu, India. Several artificial roughness features have been incorporated into the solar black-coated absorber plate for this examination. Broken ribs with semi-circular and semi-polygonal shapes are used and explicitly tested on the absorber plate. Next, the efficiency of these rib designs is contrasted with a typical flat plate DPSAH. These studies also employ three different mass flow rates (0.01 kg/s, 0.02 kg/s, and 0.03 kg/s), enabling a thorough assessment of the DPSAH system's performance at each rate. These studies' findings demonstrate that adding artificial roughness to the solar collector plate has a beneficial effect on the turbulence of fluid flows. As a result, this innovation increases the double-pass solar air heater's (DPSAH) heat transfer rate. It is noteworthy that compared to the DPSAH with flat plates, both rib designs perform better. It is important to remember that the semi-polygonal ribs function better than the semi-circular ones. The average efficiency values for the semi-polygonal rib structure are 17.1%, 18.7%, and 19.1% greater than those seen for flat plates. These efficiency values are additionally 4.4%, 7.4%, and 8.7% higher than those attained with the semi-circular rib topologies at flow rates of 0.01 kg/s, 0.02 kg/s, and 0.03 kg/s, respectively. The study goes into considerable detail on how particular rib patterns can be advantageous economically and environmentally.


Subject(s)
Solar Energy , India
3.
Environ Sci Pollut Res Int ; 30(57): 120564-120575, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37940830

ABSTRACT

Solar still is the easiest method to purifying the saline water for domestic usage, but this method needs much improvement for better performance since it has lower productivity. In this paper, an experimental investigation is completed to analyse the semi cylindrical solar productivity still. The semi-cylindrical still is incorporated with direct atomizer and scrap used as an energy storage medium. Experiments are carried out during March 2020 in Kovilpatti, the southern part of India, with a depth of 2 and 4 cm saline water. Comparative performance analysis is made for conventional semi-cylindrical still, semi-cylindrical still with an atomizer, and semi-cylindrical still with atomizer and storage materials. The experimental study shows that the productivity of still increases while decreasing the water depth. Compared with 2-cm and 4-cm depth, solar still with 2-cm depth gives promising distillate productivity. The solar productivity still having 4-cm depth of water without atomizer gives only 2670 ml; on the other side, 2-cm water depth without atomizer gives 3100-ml productivity. The maximum productivity of solar still is found on a semi-cylindrical solar still combined with atomizer and energy storage medium having 2-cm water depth. Results revealed a higher freshwater production rate of 3610 ml found while incorporating atomizer and energy storage with the solar still. The system efficiency improved up to 35.20% compared to conventional semi-cylindrical still with 4 cm of saline water depth.


Subject(s)
Solar Energy , Water Purification , Fresh Water , India , Nebulizers and Vaporizers , Saline Waters
4.
Adv Protein Chem Struct Biol ; 137: 135-159, 2023.
Article in English | MEDLINE | ID: mdl-37709373

ABSTRACT

Circadian rhythms are autonomous oscillators developed by the molecular circadian clock, essential for coordinating internal time with the external environment in a 24-h daily cycle. In mammals, this circadian clock system plays a major role in all physiological processes and severely affects human health. The regulation of the circadian clock extends beyond the clock genes to involve several clock-controlled genes. Hence, the aberrant expression of these clock genes leads to the downregulation of important targets that control the cell cycle and the ability to undergo apoptosis. This may lead to genomic instability and promotes carcinogenesis. Alteration in the clock genes and their modulation is recognized as a new approach for the development of effective treatment against several diseases, including cancer. Until now, there has been a lack of understanding of circadian rhythms and cancer disease. For that, this chapter aims to represent the core components of circadian rhythms and their function in cancer pathogenesis and progression. In addition, the clinical impacts, current clock drugs, and potential therapeutic targets have been discussed.


Subject(s)
Circadian Rhythm , Neoplasms , Humans , Animals , Circadian Rhythm/genetics , Neoplasms/genetics , Carcinogenesis , Apoptosis , Cell Cycle , Mammals
5.
J Biomol Struct Dyn ; : 1-11, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37642991

ABSTRACT

Autoinducer-2 can mediate inter- and intra-species communication signal between bacteria and these signals from AI-2 is noted from limited species of bacteria. In humans, S. pyogenes is a pathogen that causes a wide range of illnesses and can survive in the host system and transmit infection. The process by which S. pyogenes acquires the competence to live and disseminate infection remains unknown. We hypothesized that AI-2 and their receptors would play a significant role during infection, and for that present investigation provides the experimental and molecular insights. In the absence of details about the receptor LuxP and LuxQ, the screening approach provides supporting insights. The evolutionary relationship and similarities of the PBP domain (Spy 1535) and the signal transmission PDZ domain (Spy 1536) were studied in relation to their counterparts in other bacteria. Molecular docking and modeling confirmed the domain-enhanced specificity for AI-2 binding. In vitro studies showed that AI-2, which is present in the cell-free supernatant of S. pyogenes, regulates luminescence in P. luminous and biofilm development in E. coli using the LuxS reporter genes. Examination of S. pyogenes gene expression revealed modulation of virulence genes when the pathogen was exposed to V. harveyi HSL and AI-2. Therefore, S. pyogenes pathogenicity is sequentially regulated by AI-2 it acquires from other commensal bacteria. Overall, this study lays the groundwork for understanding the signalling mechanism from AI-2, which are critical to the pathogenic mechanism of S. pyogenes.Communicated by Ramaswamy H. Sarma.

6.
Brief Funct Genomics ; 22(2): 227-240, 2023 04 13.
Article in English | MEDLINE | ID: mdl-36827221

ABSTRACT

SARS-CoV-2 encodes eight accessory proteins, one of which, ORF8, has a poorly conserved sequence with SARS-CoV and its role in viral pathogenicity has recently been identified. ORF8 in SARS-CoV-2 has a unique functional feature that allows it to form a dimer structure linked by a disulfide bridge between Cys20 and Cys20 (S-S). This study provides structural characterization of natural mutant variants as well as the identification of potential drug candidates capable of binding directly to the interchain disulfide bridge. The lead compounds reported in this work have a tendency to settle in the dimeric interfaces by direct interaction with the disulfide bridge. These molecules may disturb the dimer formation and may have an inhibition impact on its potential functional role in host immune evasion and virulence pathogenicity. This work provides detailed insights on the sequence and structural variability through computational mutational studies, as well as potent drug candidates with the ability to interrupt the intermolecular disulfide bridge formed between Cys20 and Cys20. Furthermore, the interactions of ORF8 peptides complexed with MHC-1 is studied, and the binding mode reveals that certain ORF8 peptides bind to MHC-1 in a manner similar to other viral peptides. Overall, this study is a narrative of various computational approaches used to provide detailed structural insights into SARS-CoV-2 ORF8 interchain disulfide bond disruptors.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Dimerization
7.
Adv Protein Chem Struct Biol ; 133: 55-83, 2023.
Article in English | MEDLINE | ID: mdl-36707206

ABSTRACT

Secretory proteins play an important role in the tumor microenvironment and are widely distributed throughout tumor tissues. Tumor cells secrete a protein that mediates communication between tumor cells and stromal cells, thereby controlling tumor growth and affecting the success of cancer treatments in the clinic. The cancer secretome is produced by various secretory pathways and has a wide range of applications in oncoproteomics. Secretory proteins are involved in cancer development and tumor cell migration, and thus serve as biomarkers or effective therapeutic targets for a variety of cancers. Several proteomic strategies have recently been used for the analysis of cancer secretomes in order to gain a better understanding and elaborate interpretation. For instance, the development of exosome proteomics, degradomics, and tumor-host cell interaction provide clear information regarding the mechanism of cancer pathobiology. In this chapter, we emphasize the recent advances in secretory protein and the challenges in the field of secretome analysis and their clinical applications.


Subject(s)
Neoplasms , Secretory Pathway , Humans , Proteomics , Neoplasms/metabolism , Proteins/metabolism , Biomarkers/metabolism , Macromolecular Substances/metabolism , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Tumor Microenvironment
8.
Appl Biochem Biotechnol ; 195(1): 519-533, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36098931

ABSTRACT

Listeria monocytogenes have the ability to form biofilms, which aid in the contamination of food and the evasion of antimicrobials. Consumption of L. monocytogenes laden food can promote mild to severe infection in humans and cause serious health issues. Therefore, biofilm development by L. monocytogenes is considered to be a major concern for both healthcare and food safety. This study attempted to target chorismate synthase, an essential protein predicted to be involved in the biofilm pathway. Nigella sativa is renowned for its applications in folk medicine; hence, bioactive ingredients reported were used for molecular docking studies. In the absence of a three-dimensional structure of chorismate synthase from L. monocytogenes, a homology model was generated using the Modeller program. A model with the highest DOPE score was chosen and validated. The reliable model was subjected to docking studies with 30 ligands from N. sativa. From this approach, α-longipinene was unveiled as the best hit. Further in vitro studies demonstrated the antibiofilm potential of α-longipinene against L. monocytogenes. Overall, the study reveals lead molecules from N. sativa as promising antibiofilm agents against L. monocytogenes. Hence, extended investigation with lead molecules will provide sustainable strategies to prevent biofilm-mediated problems due to L. monocytogenes.


Subject(s)
Listeria monocytogenes , Nigella sativa , Humans , Listeria monocytogenes/metabolism , Molecular Docking Simulation , Biofilms
9.
Adv Protein Chem Struct Biol ; 131: 261-276, 2022.
Article in English | MEDLINE | ID: mdl-35871893

ABSTRACT

Numerous viruses have evolved mechanisms to inhibit or alter the host cell's apoptotic response as part of their coevolution with their hosts. The analysis of virus-host protein interactions require an in-depth understanding of both the viral and host protein structures and repertoires, as well as evolutionary mechanisms and pertinent biological facts. Throughout the course of a viral infection, there is constant battle for binding between virus and cellular proteins. Exogenous interfaces facilitating viral-host interactions are well known for constantly targeting and suppressing endogenous interfaces mediating intraspecific interactions, such as viral-viral and host-host connections. In these interactions, the protein-protein interactions (PPIs), are mostly shown as networks (protein interaction networks, PINs), with proteins represented as nodes and their interactions represented as edges. Host proteins with a higher degree of connectivity are more likely to interact with viral proteins. Due to technical advancements, three-dimensional interactions may now be visualized computationally utilizing molecular modeling and cryo-EM approaches. The uniqueness of viral domain repertoires, their evolution, and their activities during viral infection make viruses fascinating models for research. This chapter aims to provide readers a complete picture of the viral hijacking mechanism in protein-protein interactions.


Subject(s)
Host Microbial Interactions , Viral Proteins , Humans , Viral Proteins/chemistry
10.
J Infect Public Health ; 15(4): 379-388, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35299061

ABSTRACT

BACKGROUND: An ischemic stroke can be caused by thrombosis and ischemia, which is a major public health problem around the world, resulting in severe disability and a high death rate. The goal of this work is to examine and target various heat shock proteins (HSPs) via their interacting partners, which may have an anti-ischemic stroke impact. METHODS: Various heat shock proteins are identified and used for construction of PPI network through STRING webserver. Networks are analysed and visualized using the cytoscape for checking the protein-protein interactions. Along with this, multiple cytoscape based modules are integrated for the analysis of results, and Gene Ontology results are analysed using GOView. RESULTS: The core PPI network was revealed with 129 nodes and 1174 edges. Through Gene ontology (GO) and KEGG enrichment analysis the promising function of HSPs in two important signaling pathways were mainly recorded, representing the HSPs are necessary for repair and activations of brain cells during ischemic stroke. In addition, the study is revelation for targeting multiple HSPs via their interacting partners, which can provide anti-ischemic stroke effect. CONCLUSION: Overall, this finding provides a network-based framework for future research on HSP as therapeutic molecules for anti-ischemic stroke related applications.


Subject(s)
Heat-Shock Proteins , Ischemic Stroke , Brain , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Humans , Signal Transduction/genetics
11.
Adv Protein Chem Struct Biol ; 129: 163-188, 2022.
Article in English | MEDLINE | ID: mdl-35305718

ABSTRACT

Selectin enzymes are glycoproteins and are an important adhesion molecule in the mammalian immune system, especially in the inflammatory response and the healing process of tissues. Selectins play an important role in a variety of biological processes, including the rolling of leukocytes in endothelial cells, a process known as the adhesion cascade. It has recently been discovered and reported that the selectin mechanism plays a role in cancer and thrombosis disease. This process begins with non-covalent interactions-based selectin-ligand binding and the glycans play a role as a connector between cancer cells and the endothelium in this process. The selectin mechanism is critical for the immune system, but it is also involved in disease mechanisms, earning the selectins the nickname "Selectins-The Two Dr. Jekyll and Mr. Hyde Faces". As a result, the drug for selectins should have a multifaceted role and be a dynamic molecule that targets the disease mechanism specifically. This chapter explores the role of selectins in the disease mechanism at the mechanism level that provides the impact for identifying the selectin inhibitors. Overall, this chapter provides the molecular level insights on selectins, their ligands, involvement in normal and disease mechanisms.


Subject(s)
Endothelial Cells , Selectins , Animals , Endothelial Cells/metabolism , Humans , Leukocytes/metabolism , Ligands , Mammals/metabolism , Selectins/metabolism
12.
Saudi J Biol Sci ; 29(2): 984-991, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35197767

ABSTRACT

Nitric oxide (NO) is one of the major signalling molecules in the mammalian body playing critical role in regulation of blood pressure, cardiovascular disease including stroke, immune activation, neuronal and cell communication. Moreover, hyper production of NO by the activity of nitric oxide synthase (NOS) involved in neuropathic pain, neurodegenerative disorders and stroke. Hence, the search on small molecules from the natural sources for the inhibition of NOS is desirable in therapeutic point of view. The elevated level of NO caused by NOS enzyme become a novel target in finding new inhibitors from natural sources as antistroke agents. The present study focuses on the molecular docking of quercetin and its analogues against NOS. The active site of the enzyme was docked with the ligand and pharmacological properties were analysed. From this result, we suggest the therapeutic property of quercetin and its analogues against NOS.

13.
Curr Drug Targets ; 23(8): 782-801, 2022.
Article in English | MEDLINE | ID: mdl-34939539

ABSTRACT

BACKGROUND: Human papillomavirus (HPV), one of the most frequently transmitted viruses, causes several malignancies, including cervical cancer. AIM: Owing to its unique pathogenicity, the HPV virus can persist in the host organism for a longer duration than other viruses to complete its lifecycle. During its association with the host, HPV causes various pathological conditions affecting the immune system by evading the host's immune mechanisms, thereby leading to the progression of various diseases, including cancer. METHOD: To date, ~ 150 serotypes have been identified, and certain high-risk HPV types are known to be associated with genital warts and cervical cancer. As of now, two prophylactic vaccines are in use for the treatment of HPV infection; however, no effective antiviral drug is available for HPVassociated disease/infections. Numerous clinical and laboratory studies have been conducted to formulate an effective and specific vaccine against HPV infections and associated diseases. RESULT: As the immunological basis of HPV infection and associated disease progress persist indistinctly, deeper insights into immune evasion mechanism and molecular biology of disease would aid in developing an effective vaccine. CONCLUSION: Thus, this systematic review focuses on the immunological aspects of HPV-associated cervical cancer by uncovering immune evasion strategies adapted by HPV.


Subject(s)
Alphapapillomavirus , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Immune Evasion , Molecular Biology , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/prevention & control
14.
Saudi J Biol Sci ; 28(12): 7455-7459, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34867050

ABSTRACT

B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) are members of the tumor necrosis factor superfamily of cytokines and can induce B cell activation, differentiation, and antibody production via interaction with their receptors, including transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), B-cell maturation antigen (BCMA), and B-cell activating factor receptor (BAFF-R). Herein, we assessed the plasma protein levels of BAFF and APRIL in patients with asthma to determine whether their expression is correlated with total IgE production and examined the surface expression of BAFF/APRIL receptors on B cells. Blood samples were collected from 47 patients with controlled asthma symptoms and 20 healthy normal controls, and plasma levels of APRIL, BAFF, and total IgE protein were quantified by corresponding ELISA assays. Furthermore, lymphocytes were isolated and B cells were analyzed for the presence of BAFF-R, BCMA, and TACI receptors using flow cytometry. Our results showed that IgE, BAFF, and APRIL plasma levels were markedly increased in patients with asthma compared with healthy controls. Moreover, expression of BAFF-R and BCMA, but not that of TACI, was significantly increased in patients with asthma compared with healthy controls. Overall, the findings suggest BAFF and APRIL as key mediators of asthma, and determination of their plasma levels may be useful in monitoring asthma symptoms and treatment response.

15.
Saudi J Biol Sci ; 28(7): 3650-3659, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34220215

ABSTRACT

Bacillus anthracis is a gram positive, deadly spore forming bacteria causing anthrax and these bacteria having the complex mechanism in the cell wall envelope, which can adopt the changes in environmental conditions. In this, the membrane bound cell wall proteins are said to progressive drug target for the inhibition of Bacillus anthracis. Among the cell wall proteins, the SrtA is one of the important mechanistic protein, which mediate the ligation with LPXTG motif by forming the amide bonds. The SrtA plays the vital role in cell signalling, cell wall formation, and biofilm formations. Inhibition of SrtA leads to rupture of the cell wall and biofilm formation, and that leads to inhibition of Bacillus anthracis and thus, SrtA is core important enzyme to study the inhibition mechanism. In this study, we have examined 28 compounds, which have the inhibitory activity against the Bacillus anthracis SrtA for developing the 3D-QSAR and also, compounds binding selectivity with both open and closed SrtA conformations, obtained from 100 ns of MD simulations. The binding site loop deviate in forming the open and closed gate mechanism is investigated to understand the inhibitory profile of reported compounds, and results show the closed state active site conformations are required for ligand binding specificity. Overall, the present study may offer an opportunity for better understanding of the mechanism of action and can be aided to further designing of a novel and highly potent SrtA inhibitors.

16.
Electron. j. biotechnol ; 52: 1-12, July. 2021. tab, ilus, graf
Article in English | LILACS | ID: biblio-1283167

ABSTRACT

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a neoplasm of B-cells characterized by variable prognosis. Exploring the proteome of CLL cells may provide insights into the disease. Therefore, eleven proteomics experiments were conducted on eleven primary CLL samples. RESULTS: We reported a CLL proteome consisting of 919 proteins (false discovery rate (FDR) 1%) whose identification was based on the sequencing of two or more distinct peptides (FDR of peptide sequencing 1%). Mass spectrometry-based protein identification was validated for four different proteins using Western blotting and specific antibodies in different CLL samples. Small sizes of nucleolin (~57 kDa and ~68 kDa) showed a potential association with good prognosis CLL cells (n = 8, p < 0.01). Compared with normal B-cells, CLL cells over-expressed thyroid hormone receptor-associated protein 3 (THRAP3; n = 9; p = 0.00007), which is implicated in cell proliferation; and heterochromatin protein 1-binding protein 3 (HP1BP3; n = 10; p = 0.0002), which promotes cell survival and tumourogenesis. A smaller form of HP1BP3, which may correspond to HP1BP3 isoform-2, was specifically identified in normal B-cells (n = 10; p = 0.0001). HP1BP3 and THRAP3 predicted poor prognosis of CLL (p 0.05). Consistently, THRAP3 and HP1BP3 were found to be associated with cancer-related pathways (p 0.05). CONCLUSIONS: Our findings add to the known proteome of CLL and confirm the prognostic importance of two novel cancer-associated proteins in this disease.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Biomarkers, Tumor/analysis , Mass Spectrometry , Transcription Factors/analysis , Nuclear Proteins/analysis , Blotting, Western , Chromatography, Liquid , Proteomics , DNA-Binding Proteins/analysis
17.
Saudi J Biol Sci ; 28(2): 1257-1266, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33613055

ABSTRACT

The impact of sandstorm dust events affects local air quality and public health. These issues are becoming of greater concern in Saudi Arabia. There is a significant lack of research on airborne endotoxin exposure and analysis in the Middle East countries and no coherent body of research exists focusing on sandstorm dust in worldwide. In this study, we used a novel design of an aluminum foil plate (AFP) electrostatic dust cloth (EDC) for the passive air sampling of sandstorm dust. A total of 38 sandstorm dust samples were collected during sandstorm episodes occurring between January and April 2020 in both indoor (7 days, n = 20) and outdoor environments (24 h, n = 18). After exposure, and following an extraction procedure, bacterial endotoxin levels were measured using the Limulus Amoebocyte Lysate (LAL) gel clot method. The study highlights that the airborne endotoxin level observed was between 10 and 200 EU/m2 in both indoor and outdoor environments, during a sandstorm event. Agricultural activities and farmhouses observed higher airborne endotoxin levels. In general, increased endotoxin levels were related to the severity of the sandstorms. Given that the observed values were high as per existing guidelines for respiratory health, we recommend the setting an occupational airborne exposure limit for bacterial endotoxin. This is the first report and further studies across various sandstorm-hit regions will need to be undertaken, together with various sampling methods, in order to assess for seasonal and geographic trends.

18.
Int J Nanomedicine ; 15: 7901-7921, 2020.
Article in English | MEDLINE | ID: mdl-33116508

ABSTRACT

INTRODUCTION: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. OBJECTIVE: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. METHODS: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. RESULTS: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥4 and p≤0.008 with corrected p≤0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in "response to zinc", "response to toxic substance" and "negative regulation of growth" (corrected p≤0.05). In contrast, the repressed genes positively regulated "cell proliferation", "cell migration", "cell adhesion", "receptor signaling pathway via JAK-STAT" and "phosphatidylinositol 3-kinase signaling" (corrected p≤0.05). Lowering the FC to ≥1.5 with p≤0.05 and corrected p≤0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. CONCLUSION: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Gene Expression Profiling , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Nanoparticles , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Humans , K562 Cells , Mitochondria/drug effects , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
19.
Eur Neurol ; 83(4): 369-379, 2020.
Article in English | MEDLINE | ID: mdl-32877892

ABSTRACT

BACKGROUND: Cerebral sinus venous thrombosis (CSVT) is a relatively rare, potentially fatal neurological condition that can be frequently overlooked due to the vague nature of its clinical and radiological presentation. A literature search on PubMed using the keyword "Cerebral sinus venous thrombosis" was performed. We searched for the epidemiology, risk factors, pathophysiology, clinical features, diagnosis, and treatment of CSVT. All full-text articles in the last 10 years, in adults (>18 years), and the English language were included. We aim to give a comprehensive review of CSVT, with a primary focus on the management of the disease. SUMMARY: The literature search revealed 404 articles that met our criteria. CSVT is a relatively rare condition that accounts for approximately 1% of all forms of stroke. They can be subdivided into acute, subacute, and chronic forms based on the time of onset of clinical symptoms. It is a multifactorial disease, and the major forms of clinical presentation include isolated intracranial hypertension syndrome, focal neurological deficits, and cavernous sinus syndrome. MRI with magnetic resonance venogram (MRV) is considered the gold standard for diagnosis. Anticoagulation with heparin or low-molecular-weight heparin is the mainstay of treatment. Endovascular management is indicated for those cases with severe symptoms or worsening of symptoms despite anticoagulation therapy. Favorable outcomes have been reported in patients who receive early diagnosis and treatment. CONCLUSION: CSVT is a potentially fatal neurological condition that is often under-diagnosed due to its nonspecific presentation. Timely diagnosis and treatment can reduce morbidity and mortality, remarkably improving the outcome in affected individuals.


Subject(s)
Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/pathology , Sinus Thrombosis, Intracranial/therapy , Adult , Female , Humans , Male , Risk Factors
20.
Curr Genet ; 66(5): 1003-1017, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32613295

ABSTRACT

The endoplasmic reticulum (ER) stress potentially activates the unfolded protein response (UPR) and ER-associated protein degradation (ERAD) as quality-control mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a bridging factor and transports the misfolded proteins from the ER to the cytosol for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a toxic metal that initiates ER stress and has an impact on lipid homeostasis and this study focuses on the synergistic impact of Cd exposure and ERAD (using ubx2∆ strain). With Cd exposure in ubx2∆ strain, we observed stunted growth and induction of ER stress. The ER stress was confirmed by measuring the expression of UPR marker (Kar2p), and mRNA expression of ER stress-responsive genes (HAC1, IRE1, ERO1, and PDI1), heat shock responsive genes (HSP104 and HSP60), ERAD pathway genes (DOA10, CDC48, HRD1, and YOS9), and proteasome regulators (UBI14, and RPN4). We also observed aberrant membrane morphology with DiOC6 staining, and interrupted mitochondria with mitotracker dye using microscopic analysis. The cell's inability to relieve stress through adaptive response results in apoptosis and was assessed using acridine orange (AO)-ethidium bromide (EtBr) staining. In ubx2∆ strain, there was reduction in triacylglycerol (TAG) and lipid droplets (LDs), and increase in the phospholipids. The mRNA expression of lipid metabolic genes (LRO1, DGA1, ARE1, ARE2, and OLE1) supported the lipid pattern observed. Collectively, our data suggest that in Saccharomyces cerevisiae, the Cd exposure on ubx2∆ strain induced cellular stress and has an impact on ERAD, UPR, and LD homeostasis.


Subject(s)
Apoptosis , Cadmium/toxicity , Carrier Proteins/metabolism , Endoplasmic Reticulum Stress , Endoplasmic Reticulum-Associated Degradation , Lipid Metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/drug effects , Carrier Proteins/genetics , Endoplasmic Reticulum/metabolism , Gene Expression Regulation, Fungal , Genes, Fungal , Lipid Droplets/metabolism , Membrane Lipids/metabolism , Mitochondria/drug effects , Mitochondria/ultrastructure , Phospholipids/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae/physiology , Saccharomyces cerevisiae Proteins/genetics , Triglycerides/metabolism , Unfolded Protein Response
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