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1.
RSC Adv ; 13(28): 19119-19129, 2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37383684

ABSTRACT

Here, we outline the synthesis of a few 2-methoxy-6-((4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)(phenyl)methyl)phenol derivatives and assess their anti-inflammatory activity in macrophage cells that have been stimulated by LPS. Among these newly synthesized morpholinopyrimidine derivatives, 2-methoxy-6-((4-methoxyphenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)phenol (V4) and 2-((4-fluorophenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)-6-methoxyphenol (V8) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our findings also showed that compounds V4 and V8 dramatically reduced iNOS and cyclooxygenase mRNA expression (COX-2) in LPS-stimulated RAW 264.7 macrophage cells; western blot analysis showed that the test compounds decreased the amount of iNOS and COX-2 protein expression, hence inhibiting the inflammatory response. We find through molecular docking studies that the chemicals had a strong affinity for the iNOS and COX-2 active sites and formed hydrophobic interactions with them. Therefore, use of these compounds could be suggested as a novel therapeutic strategy for inflammation-associated disorders.

2.
Sci Rep ; 13(1): 6246, 2023 04 17.
Article in English | MEDLINE | ID: mdl-37069201

ABSTRACT

Driven by the need to biosynthesized alternate biomedical agents to prevent and treat infection, copper oxide nanoparticles (CuONPs) have surfaced as a promising avenue. Cyanobacteria-derived synthesis of CuONPs is of substantive interest as it offers an eco-friendly, cost-effective, and biocompatible route. In the present study biosynthesized CuONPs were characterized and investigated regarding their toxicity. Morphological analysis using TEM, SEM and AFM showed the spherical particle size of 20.7 nm with 96% copper that confirmed the purity of CuONPs. Biogenic CuONPs with IC50 value of 64.6 µg ml-1 showed 90% scavenging of free radicals in superoxide radical scavenging assay. CuONPs showed enhanced anti-inflammatory activity by 86% of protein denaturation with IC50 value of 89.9 µg ml-1. Biogenic CuONPs exhibited significant toxicity against bacterial strains with lowest MIC value of 62.5 µg ml-1 for B. cereus and fungal strain with a MIC value of 125 µg ml-1 for C. albicans. In addition CuONPs demonstrated a high degree of synergistic interaction when combined with standard drugs. CuONPs exhibited significant cytotoxicity against non-small cell lung cancer with an IC50 value of 100.8 µg ml-1 for A549 and 88.3 µg ml-1 for the H1299 cell line with apoptotic activities. Furthermore, biogenic CuONPs was evaluated for their photocatalytic degradation potential against methylene blue dye and were able to removed 94% dye in 90 min. Free radical scavenging analysis suggested that CuONPs assisted dye degradation was mainly induced by hydroxide radicals. Biogenic CuONPs appears as an eco-friendly and cost effective photocatalyst for the treatment of wastewater contaminated with synthetic dyes that poses threat to aquatic biota and human health. The present study highlighted the blend of biomedical and photocatalytic potential of Phormidium derived CuONPs as an attractive approach for future applications in nanomedicine and bioremediation.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Metal Nanoparticles , Nanoparticles , Humans , Copper/pharmacology , Phormidium , Nanoparticles/toxicity , Superoxides , Candida albicans , Metal Nanoparticles/toxicity
3.
J Nutr Biochem ; 110: 109130, 2022 12.
Article in English | MEDLINE | ID: mdl-35988833

ABSTRACT

Acute lung injury is a life-threatening medical problem induced by sepsis or endotoxins and may be associated with enhanced Endoplasmic reticulum stress (ER stress). Vitamin-D (Vit-D) possesses an anti-inflammatory effect; however, this specific mechanism on acute lung injury is still unknown. Here we scrutinize the mechanism of Vit-D on Acute lung injury (ALI) models and explored the Vit-D augmented miRNA's role in regulating the ER stress pathway in ALI. Sepsis was induced by CLP, and Endotoxemia was caused by lipopolysaccharide (LPS). We found that Vit-D alleviates pulmonary edema, improves lung histoarchitecture, infiltration of neutrophils, endothelial barrier in mice, and improves ER stress markers Activating Transcription Factor 6 (ATF6) and CHOP (C/EBP Homologous Protein) expression elevated by CLP/LPS induce ALI. Vit-D decreases the nitric oxide production and ATF6 in macrophages induced by LPS. Vit-D augments miR (miR-149-5p) in LPS-induce macrophages, CLP, and LPS-induced ALI models. Vit-D enhanced miRNA-149-5p when overexpressed, inhibited ER-specific ATF6 inflammatory pathway in LPS-stimulated macrophages, and improved histoarchitecture of the lung in LPS/CLP-induced mice models. This vitro and vivo studies demonstrate that Vit-D could improve ALI induced by CLP/LPS. In this regard, miR-149-5p may play a crucial role in vitamin-D inhibiting LPS/CLP induce ALI. The mechanism might be an association of increased miR-149-5p and its regulated gene target ATF6, and downstream CHOP proteins were suppressed. Thus, these findings demonstrate that the anti-inflammatory effect of Vit-D is achieved by augmentation of miRNA-149-5p expression, which may be a key physiologic mediator in the prevention and treatment of ALI.


Subject(s)
Acute Lung Injury , MicroRNAs , Sepsis , Animals , Mice , Acute Lung Injury/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/prevention & control , Anti-Inflammatory Agents , Endoplasmic Reticulum Stress , Lipopolysaccharides/toxicity , MicroRNAs/genetics , MicroRNAs/metabolism , Sepsis/complications , Vitamin D , Vitamins
4.
Genes Dis ; 9(5): 1258-1268, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35873025

ABSTRACT

Acute Lung Injury (ALI) and its severe form Acute Respiratory Distress Syndrome (ARDS) are the major cause of ICU death worldwide. ALI/ARDS is characterized by severe hypoxemia and inflammation that leads to poor lung compliance. Despite many advances in understanding and management, ALI/ARDS is still causing significant morbidity and mortality. Long non-coding RNA (lncRNA) is a fast-growing topic in lung inflammation and injury. lncRNA is a class of non-coding RNA having a length of more than 200 nucleotides. It has been a center of research for understanding the pathophysiology of various diseases in the past few years. Multiple studies have shown that lncRNAs are abundant in acute lung injury/injuries in mouse models and cell lines. By targeting these long non-coding RNAs, many investigators have demonstrated the alleviation of ALI in various mouse models. Therefore, lncRNAs show great promise as a therapeutic target in ALI. This review provides the current state of knowledge about the relationship between lncRNAs in various biological processes in acute lung injury and its use as a potential therapeutic target.

5.
RSC Adv ; 12(4): 2497-2510, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-35425239

ABSTRACT

Driven by the need to biosynthesize alternate biomedical agents to prevent and treat infection, silver nanoparticles have surfaced as a promising avenue. Cyanobacteria-derived nanomaterial synthesis is of substantive interest as it offers an eco-friendly, cost-effective, sustainable, and biocompatible route for further development. In the present study optimal conditions for synthesis of silver nanoparticles (AgNPs) were 1 : 9 v/v [cell extract: AgNO3 (1 mM)], pH 7.4, and 30 °C reaction temperatures. Synthesis of nanoparticles was monitored by UV-vis spectrophotometry and the maximum absorbance was observed at a wavelength of 420 nm. SEM with EDX analysis confirmed 96.85% silver by weight which revealed the purity of AgNPs. TEM & XRD analysis exhibited a particle size of ∼12 nm with crystalline nature. FTIR analysis confirmed the presence of possible biomolecules involved in the synthesis and stabilization of AgNPs. Decapping of AgNPs followed by SDS-PAGE, LCMS and MALDI TOF analysis elucidates the proteinaceous nature of the capping and stabilizing agent. Cyanobacterial-derived capped AgNPs showed more cytotoxicicity towards a non-small cell lung cancer (A549) cell line, free radical scavenger and an antimicrobial than de-capped AgNPs. In addition they showed significant synergistic characteristics with antibiotics and fungicides. The test revealed that the capped AgNPs were biocompatible with good anti-inflammatory properties. The blend of antimicrobial and biocompatible properties, coupled with their intrinsic "green" and facile synthesis, made these biogenic nanoparticles particularly attractive for future applications in nanomedicine.

6.
Semin Cancer Biol ; 86(Pt 2): 720-736, 2022 11.
Article in English | MEDLINE | ID: mdl-35257861

ABSTRACT

Chemokines are small secreted proteins that regulate the immune system by signaling through chemokine receptors to induce immune cell migration, motility, and infiltration into the tissue. Altered chemokine/receptor expression is associated with numerous inflammatory diseases, and more recently in non-immune cell diseases like cancer. Emerging new studies demonstrate that chemokines can directly modulate the tumor microenvironment (TME) to assist tumorigenesis by regulating proinflammatory signaling, immune cell infiltration,and metastasis. However, the diversity and complexity in the regulation of chemokine expression and how chemokine receptor signaling influences TME needs comprehensive understanding. One mechanistic pathway that has shown promising early results in targeting tumor progression is the non-coding RNAs (ncRNAs). These are widely expressed and designated as prime gene regulatory factors in tumors and the immune system. Notably, ncRNAs have been implicated in regulating chromatin stability, translation of cytoplasmic mRNAs, and the functional regulation of membrane-less nuclear bodies, which are significant pathways implicated in tumorigenesis. Tissue-specific patterns of expression of ncRNAs have suggested their role as potential cancer biomarkers, providing a suitable rationale for targeting them clinically. In this review, we discuss the recent findings which demonstrate the role of differential expression of chemokines and ncRNA in modulating TME during tumor progression. We also discuss the communication between tumor and immune effector cells via chemokine/ncRNAs and identify their potential as novel therapeutic targets.


Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/genetics , Neoplasms/pathology , RNA, Untranslated/genetics , Chemokines/genetics , Chemokines/metabolism , Cell Transformation, Neoplastic , Carcinogenesis
7.
Genes (Basel) ; 13(2)2022 01 24.
Article in English | MEDLINE | ID: mdl-35205254

ABSTRACT

Sepsis is a clinical syndrome with high mortality and morbidity rates. In sepsis, the abrupt release of cytokines by the innate immune system may cause multiorgan failure, leading to septic shock and associated complications. In the presence of a number of systemic disorders, such as sepsis, infections, diabetes, and systemic lupus erythematosus (SLE), cardiorenal syndrome (CRS) type 5 is defined by concomitant cardiac and renal dysfunctions Thus, our study suggests that certain mRNAs and unexplored pathways may pave a way to unravel critical therapeutic targets in three debilitating and interrelated illnesses, namely, sepsis, SLE, and CRS. Sepsis, SLE, and CRS are closely interrelated complex diseases likely sharing an overlapping pathogenesis caused by erroneous gene network activities. We sought to identify the shared gene networks and the key genes for sepsis, SLE, and CRS by completing an integrative analysis. Initially, 868 DEGs were identified in 16 GSE datasets. Based on degree centrality, 27 hub genes were revealed. The gProfiler webtool was used to perform functional annotations and enriched molecular pathway analyses. Finally, core hub genes (EGR1, MMP9, and CD44) were validated using RT-PCR analysis. Our comprehensive multiplex network approach to hub gene discovery is effective, as evidenced by the findings. This work provides a novel research path for a new research direction in multi-omics biological data analysis.


Subject(s)
Lupus Erythematosus, Systemic , Sepsis , Computational Biology , Gene Expression Profiling , Gene Regulatory Networks , Humans , Lupus Erythematosus, Systemic/genetics , Sepsis/genetics
8.
Bioorg Chem ; 113: 104999, 2021 08.
Article in English | MEDLINE | ID: mdl-34062406

ABSTRACT

Due to unique properties of the nanoparticles (NPs) with biocompatibility, their application as drug in drug delievery and diagnostics, the recent scientific branch nanotechnology has emerged as hope in modern medicine. Zinc oxide nanoparticles (ZnO NPs) have gained tremendous interest due to their potential use as chemotherapeutic and antimicrobial agents. They are included in the category of "generally recognized as safe (GRAS) metal oxide". There is an urgent need for developing additional sources of ZnO NPs. Therefore, in the present study 30 cyanobacterial extracts were screened for ZnO NPs synthesis.. The color change of the reaction mixture from blue to pale white indicated the synthesis of ZnO NPs. It was further confirmed by UV-Visible spectroscopy that showed the absorption peak at 372 nm. The SEM analysis during screening revealed that Oscillatoria sp. synthesized smallest ZnO NPs (~40 nm) that were further optimized for their higher yield by altering reaction conditions (pH, temperature, reaction time, concentration of extract and metal precursor). Best conditions for ZnO NPs synthesis are (0.02 M zinc nitrate, 10 ml of extract volume, pH 8, at 80 °C for 3 h). The NPs were purified through calcination at 350°C and characterized by UV-Vis, FTIR, XRD, SEM-EDAX, TEM, Zeta potential and DLS analysis. The comparative analysis of purified biogenic ZnO NPs with commercial chemically synthesized ZnO NPs (CS), exhibited their superior nature as antioxidant and anti-bacterial agent against both gram-positive and gram-negative bacteria. Synergistic effects of biogenic ZnO NPs and streptomycin additionally favored for their future use as a potential biomedical agent.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Cyanobacteria/chemistry , Metal Nanoparticles/chemistry , Zinc Oxide/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cyanobacteria/metabolism , Drug Synergism , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hydrogen Peroxide/chemistry , Metal Nanoparticles/toxicity , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Particle Size
9.
Sci Rep ; 11(1): 13507, 2021 06 29.
Article in English | MEDLINE | ID: mdl-34188065

ABSTRACT

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicines due to their high surface area and unique properties than their other forms of selenium. In this study, biogenic selenium nanoparticles (B-SeNPs) were synthesized using cyanobacteria and their bioactivities (antioxidant, antimicrobial, anticancer and biocompatibility) were determined for comparison with commercially available chemically synthesized selenium nanoparticles (C-SeNPs). Color change of reaction mixture from sky blue to orange-red indicated the synthesis of biogenic SeNPs (B-SeNPs). UV-Vis spectra of the reaction mixture exhibited peak at 266 nm. During optimization, 30 °C of temperature, 24 h of time and 1:2 concentration ratio of sodium selenite and cell extract represented the best condition for SeNPs synthesis. Various functional groups and biochemical compounds present in the aqueous extract of Anabaena variabilis NCCU-441, which may have possibly influenced the reduction process of SeNPs were identified by FT-IR spectrum and GC-MS. The synthesized cyanobacterial SeNPs were orange red in color, spherical in shape, 10.8 nm in size and amorphous in nature. The B-SeNPs showed better anti-oxidant (DPPH, FRAP, SOR and ABTS assays), anti-microbial (antibacterial and antifungal) and anti-cancer activitities along with its biocompatibility in comparison to C-SeNPs suggesting higher probability of their biomedical application.


Subject(s)
Anabaena variabilis/chemistry , Antioxidants , Metal Nanoparticles/chemistry , Selenium/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry
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