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Article ; Online: Cigarette smoke-induced galectin-3 as a diagnostic biomarker and therapeutic target in lung tissue remodeling.

Sharma, Jiten R / Dubey, Anupama / Yadav, Umesh C S

2024 Volume 339, Page(s) 122433

Abstract: Galectin-3 (Gal-3), a multifunctional carbohydrate-binding lectin, has emerged as a key player in various biological processes including inflammation, cancer, cardiovascular diseases and fibrotic disorders, however it remains unclear if Gal-3 is a ... ...

Abstract	Galectin-3 (Gal-3), a multifunctional carbohydrate-binding lectin, has emerged as a key player in various biological processes including inflammation, cancer, cardiovascular diseases and fibrotic disorders, however it remains unclear if Gal-3 is a bystander or drives lung tissue remodeling (LTR). Persistent exposure to cigarette smoke (CS) is the leading cause of oxidative and inflammatory damage to the lung tissues. CS-induced pathological increase in Gal-3 expression has been implicated in the pathogenesis of various respiratory conditions, such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. We and others have reported that CS induces Gal-3 synthesis and secretion, which modulates the pathological signaling pathways in lung epithelial cells implicating Gal-3 as a novel diagnostic marker and a factor driving LTR in CS-exposed lungs. Therefore, pharmacological interventions targeting Gal-3 and its upstream and downstream signaling pathways can help combat CS-induced LTR. Excitingly, preclinical models have demonstrated the efficacy of interventions such as Gal-3 expression inhibition, Gal-3 receptor blockade, and signaling pathways modulation open up promising avenues for future therapeutic interventions. Furthermore, targeting extracellular vesicles-mediated Gal-3 release and the potential of microRNA-based therapy are emerging as novel therapeutic approaches in CS-induced LTR and have been discussed in this article.
MeSH term(s)	Humans ; Biomarkers/metabolism ; Cigarette Smoking ; Galectin 3/metabolism ; Lung/metabolism ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/etiology ; Pulmonary Disease, Chronic Obstructive/metabolism ; Tobacco Products
Chemical Substances	Biomarkers ; Galectin 3 ; LGALS3 protein, human
Language	English
Publishing date	2024-01-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2024.122433
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Article ; Online: In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

Srivastav, Amit Kumar / Rajput, Pradeep Kumar / Jaiswal, Jyoti / Yadav, Umesh C S / Kumar, Umesh

International journal of biological macromolecules

2024 Volume 266, Issue Pt 2, Page(s) 131368

Abstract: This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a ... ...

Abstract	This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.
Language	English
Publishing date	2024-04-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.131368
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Article ; Online: Author Correction: Enhancing apoptosis-mediated anticancer activity of evodiamine through protein-based nanoparticles in breast cancer cells.

Solanki, Raghu / Rajput, Pradeep Kumar / Jodha, Bhavana / Yadav, Umesh C S / Patel, Sunita

Scientific reports

2024 Volume 14, Issue 1, Page(s) 6213

Language	English
Publishing date	2024-03-14
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56762-3
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Article: Vaccines and drugs under clinical trials for prevention and treatment of COVID-19.

Yadav, Umesh C S

Virusdisease

2021 Volume 32, Issue 1, Page(s) 13–19

Abstract: The uncertainty related to prevention and treatment of Coronavirus disease 2019 due to lack of effective vaccine candidates or drug molecules has resulted in extensive spread of infection and mortality worldwide. Although the asymptomatic or mild ... ...

Abstract	The uncertainty related to prevention and treatment of Coronavirus disease 2019 due to lack of effective vaccine candidates or drug molecules has resulted in extensive spread of infection and mortality worldwide. Although the asymptomatic or mild patients are becoming healthy with regular over-the-counter medicines and proper rest and care, for the severe patients, in the absence of definite cure, different drug combinations are being used to treat on trial basis without the assurance of efficacy and safety. This scenario has however changed now with some medicines including antiviral Remdesivir and Favipiravir and anti-inflammatory drugs like dexamethasone and tocilizumab which have shown some positive results in trials such as decreasing need of mechanical or non-invasive ventilation or mortality. Further, a number of vaccine candidates are currently in pipeline and in advance stages of clinical trials, which will enhance their prospects in determining how the disease will be controlled in the times to come. In this article, an account of the under-trial potential drugs and vaccine candidates has been provided, and their future prospects have been discussed.
Language	English
Publishing date	2021-03-22
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2846993-8
ISSN	2347-3517 ; 2347-3584
ISSN (online)	2347-3517
ISSN	2347-3584
DOI	10.1007/s13337-020-00650-7
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Article ; Online: Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Jaiswal, Jyoti / Rajput, Pradeep Kumar / Srivastav, Amit Kumar / Rao, Maddila Jagapathi / Yadav, Umesh C S / Kumar, Umesh

International journal of biological macromolecules

2024 Volume 264, Issue Pt 2, Page(s) 130679

Abstract: Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the ... ...

Abstract	Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and β-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.
MeSH term(s)	Female ; Humans ; Silymarin/pharmacology ; Silymarin/chemistry ; Zein/chemistry ; Molecular Docking Simulation ; Breast Neoplasms/drug therapy ; Nanoparticles/chemistry ; Particle Size
Chemical Substances	Silymarin ; Zein (9010-66-6)
Language	English
Publishing date	2024-03-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2024.130679
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Article ; Online: Cigarette smoke induces epithelial-to-mesenchymal transition, stemness, and metastasis in lung adenocarcinoma cells via upregulated RUNX-2/galectin-3 pathway.

Sharma, Jiten R / Agraval, Hina / Yadav, Umesh C S

Life sciences

2023 Volume 318, Page(s) 121480

Abstract: Aims: An elevated level of galectin-3, a carbohydrate-binding lectin implicated in tumorigenesis, metastasis, and epithelial-mesenchymal transition (EMT), has been found in cigarette smokers. However, the regulation of its expression and role in the ... ...

Abstract	Aims: An elevated level of galectin-3, a carbohydrate-binding lectin implicated in tumorigenesis, metastasis, and epithelial-mesenchymal transition (EMT), has been found in cigarette smokers. However, the regulation of its expression and role in the pathogenesis of CS-induced EMT and lung cancer metastasis is unclear. Here, we have investigated the mechanism of CS-induced and galectin-3-mediated EMT in airway epithelial cells (AECs). Main methods: A549 adenocarcinoma cells and primary small airway epithelial cells cultured on an air-liquid interface (ALI) were exposed to cigarette smoke extract (CSE), and MTT, trypan blue, migration, invasion, tumor spheroid and colony formation assays were performed to assess EMT phenotype. Immunoblotting was performed to assess EMT and stemness markers and other regulatory proteins. Key findings: CSE exposure affected cell survival and morphology, migration, invasion, and clonogenicity of AECs, which were concomitant with an increase in the expression of EMT markers, galectin-3, and runt-related transcription factor-2 (RUNX-2), an osteogenic transcription factor and upstream regulator of galectin-3. Chemical inhibition or silencing of RUNX-2 downregulated galectin-3 and modulated EMT marker expression, migration, invasion, and clonogenicity in CSE-exposed AECs. Recombinant human galectin-3 also induced EMT and stemness-associated changes in the AECs, and GB1107, a galectin-3 inhibitor, ameliorated these changes. Further, CSE-induced intracellular ROS enabled an increase in RUNX-2 and galectin-3 expression, which were reversed by n-acetyl-cysteine. Significance: These results provide a novel mechanistic insight into CSE-induced EMT via RUNX-2/galectin-3 axis mediated through ROS, which promoted EMT-associated changes, including invasion, migration, and stemness in AECs, which could be implicated in CS-induced lung cancer progression.
MeSH term(s)	Humans ; Epithelial-Mesenchymal Transition ; Galectin 3 ; Cigarette Smoking ; Reactive Oxygen Species ; Adenocarcinoma of Lung ; Lung Neoplasms/pathology ; Transcription Factors
Chemical Substances	Galectin 3 ; Reactive Oxygen Species ; Transcription Factors
Language	English
Publishing date	2023-02-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.121480
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Article ; Online: Integrating Synthesis, Physicochemical Characterization, and In Silico Studies of Cordycepin-Loaded Bovine Serum Albumin Nanoparticles.

Jaiswal, Jyoti / Srivastav, Amit Kumar / Rajput, Pradeep Kumar / Yadav, Umesh C S / Kumar, Umesh

Journal of agricultural and food chemistry

2023 Volume 71, Issue 32, Page(s) 12225–12236

Abstract: Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a ... ...

Abstract	Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a potential drug with known antiproliferative activity, by encapsulating it in bovine serum albumin: β-cyclodextrin nanoparticles. Cordycepin-loaded nanoparticles (CLNPs) were synthesized using the antisolvent method and characterized thoroughly using various techniques. Our dynamic light scattering measurement showed a particle size and zeta potential of 160 ± 2.75 nm and -20.21 ± 2.1 mV, respectively, for CLNPs. Transmission electron microscopy studies revealed that particles were spherical in morphology. These CLNPs showed sustained release of cordycepin with encapsulation and loading efficiency of 81.62 ± 1.5 and 27.02 ± 2.0%, respectively, based on high-performance liquid chromatography and UV-vis studies. Based on differential scanning calorimetry and zeta potential studies, CLNPs improve cordycepin stability and solubility. Our molecular simulations and binding energy calculation also showed favorable protein interaction between cordycepin, bovine serum albumin, and β-cyclodextrin, further supporting the notion of improved stability. In vitro cytotoxicity, apoptosis, and cellular uptake studies on breast cancer cells showed that the synthesized nanoparticles had greater cytotoxicity as compared to free cordycepin.
MeSH term(s)	Serum Albumin, Bovine/chemistry ; Drug Carriers/chemistry ; Deoxyadenosines/pharmacology ; Nanoparticles/chemistry ; Particle Size
Chemical Substances	Serum Albumin, Bovine (27432CM55Q) ; cordycepin (GZ8VF4M2J8) ; Drug Carriers ; Deoxyadenosines
Language	English
Publishing date	2023-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.3c03608
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Article ; Online: Visfatin-induced upregulation of lipogenesis via EGFR/AKT/GSK3β pathway promotes breast cancer cell growth.

Rajput, Pradeep Kumar / Varghese, Johnna Francis / Srivastava, Amit Kumar / Kumar, Umesh / Yadav, Umesh C S

Cellular signalling

2023 Volume 107, Page(s) 110686

Abstract: Breast cancer (BC) incidence and associated mortality have increased in tandem with the growth in obesity among the females worldwide. An adipokine, visfatin, has been shown to potentially impact glucose, lipid, and protein metabolism, and promote cancer ...

Abstract	Breast cancer (BC) incidence and associated mortality have increased in tandem with the growth in obesity among the females worldwide. An adipokine, visfatin, has been shown to potentially impact glucose, lipid, and protein metabolism, and promote cancer growth however, the mechanism underlying the effect of visfatin on lipid metabolism dysregulation contributing to BC cell survival, proliferation, and metastasis has not been elucidated. Herein, we have investigated the role of visfatin on the induction of Sterol regulatory element binding protein (SREBP-1) and its upstream and downstream mediators in MCF-7 breast cancer cells. The survival and proliferation was investigated using MTT and Trypan blue assays, cytosolic lipid accumulation was observed using Nile red staining, mRNA and protein expressions were examined using RT-qPCR and western blotting, respectively, and cell cycle analysis was performed using fluorescence-activated cell sorting. Our results indicate that visfatin increased the survival and proliferation of MCF-7 cells in a time- and dose-dependent manner and augmented lipid buildup via activation of SREBP-1 and its associated downstream lipid synthesizing enzymes, at both mRNA and protein levels in MCF-7 cells. Inhibiting SREBP-1 using fatostatin or silencing with siRNA abrogated excessive lipid deposition by suppressing the expression of genes related to lipid synthesis pathway. Further, in-silico study showed high affinity binding of visfatin with epidermal growth factor receptor (EGFR), which was confirmed in an in-vitro study where visfatin increased the phosphorylation of EGFR at tyrosine residue and activated its downstream proteins via phosphorylation of AKT and GSK3β in MCF-7 cells. Inhibition of GSK3β by phosphorylation led to increased activity of SREBP-1 and associated downstream proteins. In summary, SREBP-1 may be a critical player in visfatin-induced lipid synthesis and accumulation in BC cells via activation of EGFR/AKT/GSK3β pathway leading to increased cell survival and proliferation of BC cells.
MeSH term(s)	Female ; Humans ; Proto-Oncogene Proteins c-akt/metabolism ; Breast Neoplasms/pathology ; Lipogenesis ; Up-Regulation ; Sterol Regulatory Element Binding Protein 1/genetics ; Nicotinamide Phosphoribosyltransferase ; Glycogen Synthase Kinase 3 beta/metabolism ; ErbB Receptors/metabolism ; RNA, Messenger/metabolism ; Lipids
Chemical Substances	Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Sterol Regulatory Element Binding Protein 1 ; Nicotinamide Phosphoribosyltransferase (EC 2.4.2.12) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; ErbB Receptors (EC 2.7.10.1) ; RNA, Messenger ; Lipids ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-04-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2023.110686
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Article ; Online: Enhancing apoptosis-mediated anticancer activity of evodiamine through protein-based nanoparticles in breast cancer cells.

Solanki, Raghu / Rajput, Pradeep Kumar / Jodha, Bhavana / Yadav, Umesh C S / Patel, Sunita

Scientific reports

2024 Volume 14, Issue 1, Page(s) 2595

Abstract: In the cutting-edge era of developing precision therapeutics, nanoparticles have emerged as a potent drug delivery system. Altering the size of poorly water-soluble drugs to nanoscale could confer change in their physical properties, including enhanced ... ...

Abstract	In the cutting-edge era of developing precision therapeutics, nanoparticles have emerged as a potent drug delivery system. Altering the size of poorly water-soluble drugs to nanoscale could confer change in their physical properties, including enhanced water solubility and bioavailability. Evodiamine (EVO), a natural indolequinone alkaloid extract from Evodia rutaecarpa, has shown several important pharmacological applications, anti-cancer being one of them. Protein-based nano-drug delivery systems have gained the interest of researchers due to their better biocompatibility, biodegradability, non-immunogenicity and non-toxicity. In the present study, EVO encapsulated BSA nanoparticles (ENPs) were synthesized and characterized, which were nanoscale-sized (~ 150 nm), monodispersed, spherical shaped, and showed high entrapment efficiency (~ 86%) and controlled drug release. The in-vitro anti-cancer activity of ENPs on human breast cancer cells was dose- and time-dependent. The apoptotic molecular mechanism investigated using FACS, qRT-PCR, and western blotting analysis, revealed increased expression of p53 and Bax and decreased expression of Bcl-2. Biological studies demonstrated comparatively more efficient and targeted delivery of ENPs than pure EVO. The comprehensive physiochemical characterization and in-vitro validation collectively pinpoint ENPs as a promising avenue for harnessing the therapeutic potential of the natural anti-cancer compound EVO. The findings indicate improved cytotoxicity, positioning ENPs as a propitious strategy for advancing breast cancer treatment.
MeSH term(s)	Humans ; Female ; Cell Line, Tumor ; Breast Neoplasms/drug therapy ; Apoptosis ; Nanoparticles/chemistry ; Water ; Quinazolines
Chemical Substances	evodiamine (C01825BVNL) ; Water (059QF0KO0R) ; Quinazolines
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-51970-3
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Article ; Online: Silymarin prevents endothelial dysfunction by upregulating Erk-5 in oxidized LDL exposed endothelial cells.

Patel, Rohit / Kumar, Sanjay / Varghese, Johnna F / Singh, Navneendra / Singh, Rana P / Yadav, Umesh C S

Microvascular research

2024 Volume 153, Page(s) 104667

Abstract: Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) ... ...

Abstract	Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) has been identified as an underlying cause of ED and atherosclerosis in metabolic disorders. Silymarin (Sym), a flavonolignan, possesses various pharmacological activities however its preventive mechanism in ED warrants further investigation. Here, we have examined the effects of Sym in regulating the expression of Erk-5 and ameliorating ED using in vitro and in vivo models. Primary human umbilical vein endothelial cells (pHUVECs) viability was measured by MTT assay; mRNA and protein expression by RT-qPCR and Western blotting; tube-formation assay was performed to examine endothelialness. In in-vivo experiments, normal chow-fed mice (control) or high-fat diet (HFD)-fed mice were administered Sym or Erk-5 inhibitor (BIX02189) and body weight, blood glucose, plasma-LDL, oxLDL levels, and expression of EC markers in the aorta were examined. Sym (5 μg/ml) maintained the viability and tube-formation ability of oxLDL exposed pHUVECs. Sym increased the expression of Erk-5, vWF, and eNOS and decreased ICAM-1 at transcription and translation levels in oxLDL-exposed pHUVECs. In HFD-fed mice, Sym reduced the body weight, blood glucose, LDL-cholesterol, and oxLDL levels, and increased the levels of vWF and eNOS along with Erk-5 and decreased the level of ICAM-1 in the aorta. These data suggest that Sym could be a potent anti-atherosclerotic agent that could elevate Erk-5 level in the ECs and prevent ED caused by oxidized LDL during HFD-induced obesity in mice.
MeSH term(s)	Humans ; Animals ; Mice ; Intercellular Adhesion Molecule-1 ; Signal Transduction ; Cells, Cultured ; Silymarin/adverse effects ; Blood Glucose ; von Willebrand Factor ; Lipoproteins, LDL/toxicity ; Lipoproteins, LDL/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Atherosclerosis/drug therapy ; Atherosclerosis/prevention & control ; Atherosclerosis/chemically induced ; Body Weight
Chemical Substances	oxidized low density lipoprotein ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Silymarin ; Blood Glucose ; von Willebrand Factor ; Lipoproteins, LDL
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80307-8
ISSN	1095-9319 ; 0026-2862
ISSN (online)	1095-9319
ISSN	0026-2862
DOI	10.1016/j.mvr.2024.104667
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