121 results on '"Kesari KK"'
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2. Linking EDC-laden food consumption and modern lifestyle habits with preeclampsia: A non-animal approach to identifying early diagnostic biomarkers through biochemical alterations.
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Balu UR, Vasantharekha R, Paromita C, Ali K, Mudgal G, Kesari KK, and Seetharaman B
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- Female, Humans, Pregnancy, Adult, Young Adult, Surveys and Questionnaires, Pre-Eclampsia diagnosis, Pre-Eclampsia blood, Biomarkers blood, Life Style, Endocrine Disruptors
- Abstract
Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension with or without proteinuria and/or end-organ damage, and it may be influenced by exposure to endocrine-disrupting chemicals present in processed foods and modern lifestyles. This study explores the potential link using a non-animal approach to identify early diagnostic biomarkers for preeclampsia. Seventy pregnant women aged 21-41 years participated, and completed questionnaires assessing socio-demographic factors, Suboptimal Health Status Questionnaire scores for fatigue, digestive, cardiovascular, immune, and mental health issues, and exposure to endocrine-disrupting chemicals from processed food consumption and daily product use. Peripheral blood samples were analyzed for hormone profiles, complete blood count, and liver function tests (LFT). Statistical analysis revealed that mothers above 27 years old, with a Body Mass Index exceeding 32.59 Kg/m
2 , and a Mean Arterial Pressure of 108.5 mmHg exhibited a potential obesogenic effect on preeclampsia development. Socio-demographic factors like, lower economic class, housewife status, primiparous pregnancy, non-graduate education, and rural residence were significantly associated with results. Analysis of biochemical parameters revealed that serum creatinine, blood urea, total protein, platelet count, blood urea nitrogen, bilirubin profile, LFT profile, and thyroid profile showed potential detrimental effects on kidney, liver, muscle, and thyroid function in preeclampsia patients. Notably, PC, serum urea, bilirubin, total protein, serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), and thyroid stimulating hormone (TSH) levels were significantly associated with preeclampsia in individuals reporting higher exposure to endocrine disrupting chemicals (EDCs). Minor biochemical alterations were also observed with dairy product consumption. SHS-25 analysis indicated a significant increase in fatigue, and digestive, cardiovascular, immune, and mental health-related issues in patients. Probably, biochemical alterations due to EDC exposure from processed foods and modern lifestyle habits contribute to organ dysfunction in preeclampsia. Identifying these potential biomarkers may pave the way for the development of non-invasive, early diagnostic tools for improved preeclampsia management. This research emphasizes the importance of non-animal testing methods for assessing EDC-related health risks in pregnancy and contributes to the advancement of early PE diagnosis strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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3. An opinion on advanced cancer immunotherapy through innovations in PD-1 inhibitor delivery systems.
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Gupta PK, Tiwari H, Mishra R, Balakrishnan K, Singh S, Kumar S, Kesari KK, and Krishnan S
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- 2024
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4. Cutting edge technology for wastewater treatment using smart nanomaterials: recent trends and futuristic advancements.
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Sharma A, Goel H, Sharma S, Rathore HS, Jamir I, Kumar A, Thimmappa SC, Kesari KK, and Kashyap BK
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- Water Pollutants, Chemical, Wastewater chemistry, Nanostructures, Water Purification methods, Waste Disposal, Fluid methods
- Abstract
Water is a vital component of our existence. Many human activities, such as improper waste disposal from households, industries, hospitals, and synthetic processes, are major contributors to the contamination of water streams. It is the responsibility of every individual to safeguard water resources and reduce pollution. Among the various available wastewater treatment (WWT) methods, smart nanomaterials stand out for their effectiveness in pollutant removal through absorption and adsorption. This paper examines the application of valuable smart nanomaterials in treating wastewater. Various nanomaterials, including cellulose nanocrystals (CNC), cellulose nanofibrils (CNF), nanoadsorbents, nanometals, nanofilters, nanocatalysts, carbon nanotubes (CNTs), nanosilver, nanotitanium dioxide, magnetic nanoparticles, nanozero-valent metallic nanoparticles, nanocomposites, nanofibers, and quantum dots, are identified as promising candidates for WWT. These smart nanomaterials efficiently eliminate toxic substances, microplastics, nanoplastics, and polythene particulates from wastewater. Additionally, the paper discusses comparative studies on the purification efficiency of nanoscience technology versus conventional methods., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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5. Corrigendum to "Cellular landscaping of cisplatin resistance in cervical cancer" Biomed. Pharmacother. 153(2022) 113345.
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Bhattacharjee R, Dey T, Kumar L, Kar S, Sarkar R, Ghorai M, Malik S, Jha NK, Vellingiri B, Kesari KK, Pérez de la Lastra JM, and Dey A
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- 2024
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6. Alginate-Chitosan Biodegradable and Biocompatible Based Hydrogel for Breast Cancer Immunotherapy and Diagnosis: A Comprehensive Review.
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Patra P, Upadhyay TK, Alshammari N, Saeed M, and Kesari KK
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- Humans, Female, Materials Testing, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Particle Size, Animals, Chitosan chemistry, Alginates chemistry, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Hydrogels chemistry, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Immunotherapy
- Abstract
Breast cancer is the most common type of cancer and the second leading cause of cancer-related mortality in females. There are many side effects due to chemotherapy and traditional surgery, like fatigue, loss of appetite, skin irritation, and drug resistance to cancer cells. Immunotherapy has become a hopeful approach toward cancer treatment, generating long-lasting immune responses in malignant tumor patients. Recently, hydrogel has received more attention toward cancer therapy due to its specific characteristics, such as decreased toxicity, fewer side effects, and better biocompatibility drug delivery to the particular tumor location. Researchers globally reported various investigations on hydrogel research for tumor diagnosis. The hydrogel-based multilayer platform with controlled nanostructure has received more attention for its antitumor effect. Chitosan and alginate play a leading role in the formation of the cross-link in a hydrogel. Also, they help in the stability of the hydrogel. This review discusses the properties, preparation, biocompatibility, and bioavailability of various research and clinical approaches of the multipolymer hydrogel made of alginate and chitosan for breast cancer treatment. With a focus on cases of breast cancer and the recovery rate, there is a need to find out the role of hydrogel in drug delivery for breast cancer treatment.
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- 2024
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7. Biological effects of vanillic acid, iso-vanillic acid, and orto-vanillic acid as environmental pollutants.
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Matejczyk M, Ofman P, Juszczuk-Kubiak E, Świsłocka R, Shing WL, Kesari KK, Prakash B, and Lewandowski W
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- Environmental Pollutants toxicity, Staphylococcus aureus drug effects, Candida albicans drug effects, Microbial Sensitivity Tests, Mutagenicity Tests, Anti-Bacterial Agents toxicity, Anti-Bacterial Agents pharmacology, Anti-Infective Agents toxicity, Anti-Infective Agents pharmacology, Vanillic Acid pharmacology, Vanillic Acid toxicity, Escherichia coli drug effects, Oxidative Stress drug effects
- Abstract
Vanillic acid (4-hydroxy-3-methoxybenzoic acid) (VA) is a natural benzoic acid derivative commonly found in herbs, rice, maize, and some fruits and vegetables. However, due to the wide use of VA in various industrial sectors, its presence in the environment might harm living organisms. This study evaluated the toxicity of VA and its isomers, iso-VA and orto-VA. Firstly, the antimicrobial effect of VA and its isomers iso-VA and orto-VA (in doses of 1000; 100, 10, 1; 0.1; 0.01 mg/L) against Escherichia coli, Sarcina spp., Enterobacter homaechei, Staphylococcus aureus and Candida albicans were identified. The toxic effect and protein degradation potential of VA and its isomers were determined using E. coli grpE:luxCDABE and lac:luxCDABE biosensor strains. However, the genotoxicity and oxidative stress generation were assessed with the E. coli recA:luxCDABE biosensor and E. coli strain. The results showed that VA, iso-VA, and orto-VA exhibited antimicrobial activity against all tested bacterial strains. However, VA's antimicrobial effect differed from iso-VA and orto-VA. Similar toxic, genotoxic, and oxidative stress-inducing effects were observed for VA and its isomers. Each compound exhibited toxicity, cellular protein degradation, and genotoxic activity against E. coli grpE:luxCDABE, E. coli lac:luxCDABE, and E. coli recA:luxCDABE strains. Analysis of reactive oxygen species (ROS) generation within E. coli cells highlighted oxidative stress as a contributing factor to the toxicity and genotoxicity of VA and its isomers. While the findings suggest potential applications of VA compounds as food preservatives, their presence in the environment raises concerns regarding the risks posed to living organisms due to their toxic and genotoxic characteristics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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8. Intranasal Delivery of Carvedilol- and Quercetin-Encapsulated Cationic Nanoliposomes for Cardiovascular Targeting: Formulation and In Vitro and Ex Vivo Studies.
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Kar S, Das SS, Kundu S, Sahu BD, Kumar KJ, Kesari KK, and Singh SK
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- Animals, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Materials Testing, Rats, Cations chemistry, Antioxidants chemistry, Antioxidants pharmacology, Antioxidants administration & dosage, Cell Survival drug effects, Carvedilol chemistry, Carvedilol pharmacology, Carvedilol administration & dosage, Quercetin chemistry, Quercetin administration & dosage, Quercetin pharmacology, Liposomes chemistry, Administration, Intranasal, Particle Size, Nanoparticles chemistry
- Abstract
Carvedilol (CVD), an adrenoreceptor blocker, is a hydrophobic Biopharmaceutics Classification System class II drug with poor oral bioavailability due to which frequent dosing is essential to attain pharmacological effects. Quercetin (QC), a polyphenolic compound, is a potent natural antioxidant, but its oral dosing is restricted due to poor aqueous solubility and low oral bioavailability. To overcome the common limitations of both drugs and to attain synergistic cardioprotective effects, we formulated CVD- and QC-encapsulated cationic nanoliposomes (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. We designed CVD- and QC-loaded cationic nanoliposomal (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. In vitro drug release studies of CVD/QC-L.O.F. (16.25%) exhibited 18.78 ± 0.57% of QC release and 91.38 ± 0.93% of CVD release for 120 h. Ex vivo nasal permeation studies of CVD/QC-L.O.F. demonstrated better permeation of QC (within 96 h), i.e., 75.09% compared to in vitro drug release, whereas CVD permeates within 48 h, indicating the better interaction between cationic NLPs and the negatively charged biological membrane. The developed nasal gel showed a sufficient mucoadhesive property, good spreadability, higher firmness, consistency, and cohesiveness, indicating suitability for membrane application and intranasal administration. CVD-NLPs, QC-NLPs, and CVD/QC-NLPs were evaluated for in vitro cytotoxicity, in vitro ROS-induced cell viability assessment, and a cellular uptake study using H9c2 rat cardiomyocytes. The highest in vitro cellular uptake of CVD/QC-cationic NLPs by H9c2 cells implies the benefit of QC loading within the CVD nanoliposomal carrier system and gives evidence for better interaction of NLPs carrying positive charges with the negatively charged biological cells. The in vitro H
2 O2 -induced oxidative stress cell viability assessment of H9c2 cells established the intracellular antioxidant activity and cardioprotective effect of CVD/QC-cationic NLPs with low cytotoxicity. These findings suggest the potential of cationic NLPs as a suitable drug delivery carrier for CVD and QC combination for the intranasal route in the treatment of various cardiovascular diseases like hypertension, angina pectoris, etc. and for treating neurodegenerative disorders.- Published
- 2024
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9. Therapeutic Implications of Dietary Polyphenols-Loaded Nanoemulsions in Cancer Therapy.
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Tomar R, Das SS, Balaga VKR, Tambe S, Sahoo J, Rath SK, Ruokolainen J, and Kesari KK
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- Humans, Antioxidants chemistry, Signal Transduction, Polyphenols pharmacology, Polyphenols chemistry, Neoplasms metabolism
- Abstract
Cancer is one of the major causes of death worldwide, even the second foremost cause related to non-communicable diseases. Cancer cells typically possess several cellular and biological processes including, persistence, propagation, differentiation, cellular death, and expression of cellular-type specific functions. The molecular picture of carcinogenesis and progression is unwinding, and it appears to be a tangled combination of processes occurring within and between cancer cells and their surrounding tissue matrix. Polyphenols are plant secondary metabolites abundant in fruits, vegetables, cereals, and other natural plant sources. Natural polyphenols have implicated potential anticancer activity by various mechanisms involved in their antitumor action, including modulation of signaling pathways majorly related to cellular proliferation, differentiation, relocation, angiogenesis, metastatic processes, and cell death. The applications of polyphenols have been limited due to the hydrophobic nature and lower oral bioavailability that could be possibly overcome through encapsulating them into nanocarrier-mediated delivery systems, leading to improved anticancer activity. Nanoemulsions (NEs) possess diverse feasible properties, including greater surface area, modifiable surficial charge, higher half-life, site-specific targeting, and formulation imaging capability necessary to create a practical therapeutic impact, and have drawn increased attention in cancer therapy research. This review has summarized and discussed the basic concepts, classification, delivery approaches, and anticancer mechanism of various polyphenols and polyphenols-encapsulated nanoemulsions with improved cancer therapy.
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- 2024
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10. Editorial: Hormonal imbalance-associated oxidative stress and protective benefits of nutritional antioxidants.
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Sahoo DK, Samanta L, Kesari KK, and Mukherjee S
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- Humans, Oxidative Stress, Reactive Oxygen Species, Antioxidants therapeutic use, Antioxidants metabolism, Endocrine System Diseases
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2024
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11. Emerging Trends in Zinc Ferrite Nanoparticles for Biomedical and Environmental Applications.
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Garg J, Chiu MN, Krishnan S, Kumar R, Rifah M, Ahlawat P, Jha NK, Kesari KK, Ruokolainen J, and Gupta PK
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- Ferric Compounds chemistry, Drug Delivery Systems, Zinc, Nanoparticles chemistry
- Abstract
Over the last few decades, the application of nanoparticles (NPs) gained immense attention towards environmental and biomedical applications. NPs are ultra-small particles having size ranges from 1 to 100 nm. NPs loaded with therapeutic or imaging compounds have proved a versatile approach towards healthcare improvements. Among various inorganic NPs, zinc ferrite (ZnFe
2 O4 ) NPs are considered as non-toxic and having an improved drug delivery characteristics . Several studies have reported broader applications of ZnFe2 O4 NPs for treating carcinoma and various infectious diseases. Additionally, these NPs are beneficial for reducing organic and inorganic environmental pollutants. This review discusses about various methods to fabricate ZnFe2 O4 NPs and their physicochemical properties. Further, their biomedical and environmental applications have also been explored comprehensively., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2024
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12. In Vivo Toxicological Analysis of the ZnFe 2 O 4 @poly( t BGE- alt -PA) Nanocomposite: A Study on Fruit Fly.
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Chauhan S, Naik S, Kumar R, Ruokolainen J, Kesari KK, Mishra M, and Gupta PK
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Recently, the use of hybrid nanomaterials (NMs)/nanocomposites has widely increased for the health, energy, and environment sectors due to their improved physicochemical properties and reduced aggregation behavior. However, prior to their use in such sectors, it is mandatory to study their toxicological behavior in detail. In the present study, a ZnFe
2 O4 @poly( t BGE- alt -PA) nanocomposite is tested to study its toxicological effects on a fruit fly model. This nanocomposite was synthesized earlier by our group and physicochemically characterized using different techniques. In this study, various neurological, developmental, genotoxic, and morphological tests were carried out to investigate the toxic effects of nanocomposite on Drosophila melanogaster . As a result, an abnormal crawling speed of third instar larvae and a change in the climbing behavior of treated flies were observed, suggesting a neurological disorder in the fruit flies. DAPI and DCFH-DA dyes analyzed the abnormalities in the larva's gut of fruit flies. Furthermore, the deformities were also seen in the wings and eyes of the treated flies. These obtained results suggested that the ZnFe2 O4 @poly( t BGE- alt -PA) nanocomposite is toxic to fruit flies. Moreover, this is essential to analyze the toxicity of this hybrid NM again in a rodent model in the future., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)- Published
- 2024
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13. Characterization and Exploration of Placket-Burman-Designed Porous Calcium Carbonate (Vaterite) Microparticles.
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Singh A, Das SS, Verma PRP, Ruokolainen J, Kesari KK, and Singh SK
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The objective of the research was to identify significant variables that impact the porosity-related properties of CaCO
3 particles. The Placket-Burman design was employed to screen multiple variables, including pH, molar concentrations of calcium chloride and sodium carbonate, temperature, concentration of Gelucire 44/14, Cremophor RH40, Solutol HS15, Labrasol, mixing rate, reaction time, and order of addition. The response variables were surface area, pore radius, and pore volume. Influential methodologies such as XRD, FTIR, Raman spectroscopy, and TGA were utilized to validate the precipitate type. The BET surface area ranged from 1.5 to 16.14 m2 /g, while the pore radius varied from 2.62 to 6.68 nm, and the pore volume exhibited a range of 2.43 to 37.97 cc/gm. Vaterite structures with spherical mesoporous characteristics were observed at high pH, whereas calcite formations occurred at low pH. The order of addition impacted the surface area but did not affect the pore volume. To maximize the surface area, a lower reaction time and molar concentrations of sodium carbonate were found to be advantageous. The pore radius was influenced by the pH, surfactants, and reaction conditions. The sediments were categorized based on the percentage of vaterite formation. The instrumental techniques effectively characterized the precipitates and provided a valuable complementary analysis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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14. Role of Immunological Cells in Hepatocellular Carcinoma Disease and Associated Pathways.
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Aasarey R, Yadav K, Kashyap BK, Prabha S, Kumar P, Kumar A, Ruokolainen J, and Kesari KK
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Hepatocellular carcinoma (HCC) remains one of the predominant causes of cancer-related mortality across the globe. It is attributed to obesity, excessive alcohol consumption, smoking, and infection by the hepatitis virus. Early diagnosis of HCC is essential, and local treatments such as surgical excision and percutaneous ablation are effective. Palliative systemic therapy, primarily with the tyrosine kinase inhibitor Sorafenib, is used in advanced cases. However, the prognosis for advanced HCC remains poor. This Review additionally describes the pathophysiological mechanisms of HCC, which include aberrant molecular signaling, genomic instability, persistent inflammation, and the paradoxical position of the immune system in promoting and suppressing HCC. The paper concludes by discussing the growing body of research on the relationship between mitochondria and HCC, suggesting that mitochondrial dysfunction may contribute to the progression of HCC. This Review focuses on immunological interactions between different mechanisms of HCC progression, including obesity, viral infection, and alcohol consumption., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
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- 2023
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15. Editorial: Omics for infertility and contraception: two sides of same coin.
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Jena SR, Mohanty G, Kesari KK, Durairajanayagam D, and Samanta L
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Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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- 2023
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16. Light-Driven Depolymerization of Cellulosic Biomass into Hydrocarbons.
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Negi A and Kesari KK
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Cellulose and hemicellulose are the main constituents of lignocellulosic biomass. Chemical derivatization of lignocellulosic biomass leads to a range of C5 and C6 organic compounds. These C5 and C6 compounds are valuable precursors (or fine chemicals) for developing sustainable chemical processes. Therefore, depolymerization of cellulose and hemicellulose is essential, leading to the development of various materials that have applications in biomaterial industries. However, most depolymerized processes for cellulose have limited success because of its structural quality: crystallinity, high hydrogen-bond networking, and mild solubility in organic and water. As a result, various chemical treatments, acidic (mineral or solid acids) and photocatalysis, have developed. One of the significant shortcomings of acidic treatment is that the requirement for high temperatures increases the commercial end cost (energy) and hampers product selectivity. For example, a catalyst with prolonged exposure to high temperatures damages the catalyst surface over time; therefore, it cannot be used for iterative cycles. Photocatalysts provide ample application to overcome such flaws as they do not require high temperatures to perform efficient catalysis. Various photocatalysts have shown efficient cellulosic biomass conversion into its C6 and C5 hydrocarbons and the production of hydrogen (as a green energy component). For example, TiO
2 -based photocatalysts are the most studied for biomass valorization. Herein, we discussed the feasibility of a photocatalyst with application to cellulosic biomass hydrolysis.- Published
- 2023
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17. Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.
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Chowdhary S, Deka R, Panda K, Kumar R, Solomon AD, Das J, Kanoujiya S, Gupta AK, Sinha S, Ruokolainen J, Kesari KK, and Gupta PK
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- Humans, Herpesvirus 4, Human, Carcinogenesis, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Epstein-Barr Virus Infections drug therapy, Neoplasms drug therapy, Neoplasms prevention & control, Neoplasms pathology
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Human viral oncogenesis is a complex phenomenon and a major contributor to the global cancer burden. Several recent findings revealed cellular and molecular pathways that promote the development and initiation of malignancy when viruses cause an infection. Even, antiviral treatment has become an approach to eliminate the viral infections and prevent the activation of oncogenesis. Therefore, for a better understanding, the molecular pathogenesis of various oncogenic viruses like, hepatitis virus, human immunodeficiency viral (HIV), human papillomavirus (HPV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV), could be explored, especially, to expand many potent antivirals that may escalate the apoptosis of infected malignant cells while sparing normal and healthy ones. Moreover, contemporary therapies, such as engineered antibodies antiviral agents targeting signaling pathways and cell biomarkers, could inhibit viral oncogenesis. This review elaborates the recent advancements in both natural and synthetic antivirals to control viral oncogenesis. The study also highlights the challenges and future perspectives of using antivirals in viral oncogenesis.
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- 2023
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18. Crosstalk between long noncoding RNA and microRNA in Cancer.
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Bhattacharjee R, Prabhakar N, Kumar L, Bhattacharjee A, Kar S, Malik S, Kumar D, Ruokolainen J, Negi A, Jha NK, and Kesari KK
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- Humans, Neovascularization, Pathologic genetics, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, MicroRNAs metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Neoplasms genetics, Neoplasms pathology
- Abstract
miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management., (© 2023. The Author(s).)
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- 2023
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19. Recent updates on correlation between reactive oxygen species and synbiotics for effective management of ulcerative colitis.
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Ashique S, Mishra N, Garg A, Sibuh BZ, Taneja P, Rai G, Djearamane S, Wong LS, Al-Dayan N, Roychoudhury S, Kesari KK, Slama P, Roychoudhury S, and Gupta PK
- Abstract
Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ashique, Mishra, Garg, Sibuh, Taneja, Rai, Djearamane, Wong, Al-Dayan, Roychoudhury, Kesari, Slama, Roychoudhury and Gupta.)
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- 2023
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20. Biopolymer-Capped Pyrazinamide-Loaded Colloidosomes: In Vitro Characterization and Bioavailability Studies.
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Singh A, Das SS, Ruokolainen J, Kesari KK, and Singh SK
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This study aimed to prepare colloidosome particles loaded with pyrazinamide (PZA). These drug-loaded colloidosomes were prepared using an in situ gelation technique using a central composite design with a shell made of calcium carbonate (CaCO
3 ) particles. Optimal amounts of 150 mg of CaCO3 , sodium alginate (2%), and 400 mg of poly(3-hydroxybutyrate- co -3-hydroxy valerate) (PHBV) concentration resulted in the maximum drug loading and efficient release profile. Field emission scanning electron microscopy results showed spherical porous particles with a good coating of the PHBV polymer. Additionally, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric and differential thermal analysis (TGA-DTA), and X-ray diffraction (XRD) analysis showed good compatibility between the drug and excipients. The pharmacokinetic studies demonstrated that the drug-loaded colloidosomes resulted in 4.26 times higher plasma drug concentrations with Cmax values of 32.386 ± 2.744 mcg/mL (PZA solution) and 115.868 ± 53.581 mcg/mL (PZA-loaded colloidosomes) and AUC0- t values of 61.24 mcg-h/mL (PZA solution) and 260.9 mcg-h/mL (PZA-loaded colloidosomes), indicating that colloidosomes have the potential to be effective drug carriers for delivering PZA to the target site., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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21. MicroRNAs-Based Theranostics against Anesthetic-Induced Neurotoxicity.
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Minz R, Sharma PK, Negi A, and Kesari KK
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Various clinical reports indicate prolonged exposure to general anesthetic-induced neurotoxicity (in vitro and in vivo). Behavior changes (memory and cognition) are compilations commonly cited with general anesthetics. The ability of miRNAs to modulate gene expression, thereby selectively altering cellular functions, remains one of the emerging techniques in the recent decade. Importantly, engineered miRNAs (which are of the two categories, i.e., agomir and antagomir) to an extent found to mitigate neurotoxicity. Utilizing pre-designed synthetic miRNA oligos would be an ideal analeptic approach for intervention based on indicative parameters. This review demonstrates engineered miRNA's potential as prophylactics and/or therapeutics minimizing the general anesthetics-induced neurotoxicity. Furthermore, we share our thoughts regarding the current challenges and feasibility of using miRNAs as therapeutic agents to counteract the adverse neurological effects. Moreover, we discuss the scientific status and updates on the novel neuro-miRNAs related to therapy against neurotoxicity induced by amyloid beta (Aβ) and Parkinson's disease (PD).
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- 2023
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22. Development of chemically synthesized hydroxyapatite composite with reduced graphene oxide for enhanced mechanical properties.
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Flora B, Kumar R, Tiwari P, Kumar A, Ruokolainen J, Narasimhan AK, Kesari KK, Gupta PK, and Singh A
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- Durapatite chemistry, Compressive Strength, Graphite chemistry, Nanoparticles chemistry
- Abstract
A successful attempt has been made to improve the mechanical properties of Hydroxyapatite (HAp) and reduced graphene oxide (rGO) composite nanoparticles (NPs). Various proportions of HAp and rGO were synthesized to improve the mechanical properties. HAp NPs were prepared using the wet precipitation method and further calcined to form crystalline particles. The physicochemical characterization of the HAp NPs revealed that the crystalline size and percentage of crystallinity were calculated to be 42.49 ± 1.2 nm and 44% post calcination. Furthermore, the rGO-HA composites were prepared using ball milling and obtained in the shape of pellets with different ratios of rGO (10, 20, 30, 40, 50% wt.). The mechanical properties have been evaluated through a Universal testing machine. Compared to calcined HAp (cHAp), the strength of variants significantly enhanced with the increased concentration of rGO. The compressive strength of HA-rGO with the ratio of the concentration of 60:40% by weight is a maximum of about 10.39 ± 0.43 MPa. However, the porosity has also been bolstered by increasing the concentration of rGO, which has been evaluated through the liquid displacement method. The mean surface roughness of the composites has also been evaluated from the images through Image J (an image analysis program)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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23. Long-acting biodegradable implants for osteoporosis management: transforming the landscape of bisphosphonates delivery.
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Tambe S, Kesari KK, Mishra YK, Amin P, and Das SS
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- Humans, Absorbable Implants, Drug Delivery Systems, Diphosphonates therapeutic use, Osteoporosis drug therapy
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- 2023
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24. Smart Nanomaterials in Cancer Theranostics: Challenges and Opportunities.
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Kashyap BK, Singh VV, Solanki MK, Kumar A, Ruokolainen J, and Kesari KK
- Abstract
Cancer is ranked as the second leading cause of death globally. Traditional cancer therapies including chemotherapy are flawed, with off-target and on-target toxicities on the normal cells, requiring newer strategies to improve cell selective targeting. The application of nanomaterial has been extensively studied and explored as chemical biology tools in cancer theranostics. It shows greater applications toward stability, biocompatibility, and increased cell permeability, resulting in precise targeting, and mitigating the shortcomings of traditional cancer therapies. The nanoplatform offers an exciting opportunity to gain targeting strategies and multifunctionality. The advent of nanotechnology, in particular the development of smart nanomaterials, has transformed cancer diagnosis and treatment. The large surface area of nanoparticles is enough to encapsulate many molecules and the ability to functionalize with various biosubstrates such as DNA, RNA, aptamers, and antibodies, which helps in theranostic action. Comparatively, biologically derived nanomaterials perceive advantages over the nanomaterials produced by conventional methods in terms of economy, ease of production, and reduced toxicity. The present review summarizes various techniques in cancer theranostics and emphasizes the applications of smart nanomaterials (such as organic nanoparticles (NPs), inorganic NPs, and carbon-based NPs). We also critically discussed the advantages and challenges impeding their translation in cancer treatment and diagnostic applications. This review concludes that the use of smart nanomaterials could significantly improve cancer theranostics and will facilitate new dimensions for tumor detection and therapy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)
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- 2023
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25. Cell Phone Radiation Exposure Limits and Engineering Solutions.
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Héroux P, Belyaev I, Chamberlin K, Dasdag S, De Salles AAA, Rodriguez CEF, Hardell L, Kelley E, Kesari KK, Mallery-Blythe E, Melnick RL, Miller AB, Moskowitz JM, and On Behalf Of The International Commission On The Biological Effects Of Electromagnetic Fields Icbe-Emf
- Subjects
- Humans, Radio Waves adverse effects, Communication, Radiation Exposure, Cell Phone
- Abstract
In the 1990s, the Institute of Electrical and Electronics Engineers (IEEE) restricted its risk assessment for human exposure to radiofrequency radiation (RFR) in seven ways: (1) Inappropriate focus on heat, ignoring sub-thermal effects. (2) Reliance on exposure experiments performed over very short times. (3) Overlooking time/amplitude characteristics of RFR signals. (4) Ignoring carcinogenicity, hypersensitivity, and other health conditions connected with RFR. (5) Measuring cellphone Specific Absorption Rates (SAR) at arbitrary distances from the head. (6) Averaging SAR doses at volumetric/mass scales irrelevant to health. (7) Using unrealistic simulations for cell phone SAR estimations. Low-cost software and hardware modifications are proposed here for cellular phone RFR exposure mitigation: (1) inhibiting RFR emissions in contact with the body, (2) use of antenna patterns reducing the Percent of Power absorbed in the Head (PPHead) and body and increasing the Percent of Power Radiated for communications (PPR), and (3) automated protocol-based reductions of the number of RFR emissions, their duration, or integrated dose. These inexpensive measures do not fundamentally alter cell phone functions or communications quality. A health threat is scientifically documented at many levels and acknowledged by industries. Yet mitigation of RFR exposures to users does not appear as a priority with most cell phone manufacturers.
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- 2023
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26. Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.
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Sachdeva B, Sachdeva P, Negi A, Ghosh S, Han S, Dewanjee S, Jha SK, Bhaskar R, Sinha JK, Paiva-Santos AC, Jha NK, and Kesari KK
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- Humans, Chitin, Drug Delivery Systems, Biopolymers, Chitosan therapeutic use, Nanoparticles, Neoplasms drug therapy, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use
- Abstract
Chitin is the second most abundant biopolymer consisting of N -acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.
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- 2023
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27. Radical scavenging activity of Chlorophytum borivilianum L. root extract and its protective role in cauda epididymal sperm integrity in Mus musculus after gamma irradiation.
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Vyas R, Kesari KK, Lukac N, Slama P, Roychoudhury S, and Sisodia R
- Abstract
Background: Chlorophytum borivilianum L. is a recognized herbal medicine for the management of impotency in South Asian countries. In Ayurveda , it is used for the management of multiple health conditions, including diabetes, infection, and cardiovascular diseases. Parts of the plant have been used as excellent antioxidants and scavengers of free radicals. Since oxidative stress plays an important role in spermatogenesis and fertility in male populations, this study evaluated the role of ethanolic extract of C. borivilianum roots in epididymal sperm maturation against adversities posed by ionizing gamma irradiation. Materials and methods: Antioxidant potential of C . borivilianum root extract (CRE) was evaluated through DPPH (2,2-diphenylpicrylhydrazyl) and NO (nitric oxide) scavenging assays. Four groups of healthy Swiss albino mice were constituted, which were labeled as follows: Group I: sham control, Group II: 7-day pre-treatment with 50 mg/kg CRE, Group III: 6 Gy irradiation without pre-treatment, and Group IV: 7-day pre-treatment with 50 mg/kg CRE and 6 Gy irradiation on day 7. Swiss albino mice were observed for 30 days and later sacrificed to evaluate sperm quality parameters. Results: CRE showed a remarkable antioxidant potential with IC
50 values of 46.37 μg/ml and 98.39 μg/ml for DPPH and NO, respectively. A significant decline ( p < 0.001) in cauda epididymal sperm count, motility, and viability was observed in Group III animals. Group IV also showed a substantial decline ( p < 0.01) in all three parameters compared to Group I; nonetheless, these were significantly higher than Group III. Morphological alterations indicated a coiled and bent tail, with the presence of cytoplasmic droplets in Group III, which declined substantially in Group IV. The ultrastructure of sperm indicated higher curvature of hook in Group III than Group IV, indicating specific interferences in the sperm maturation process. Conclusion: It was concluded that pre-treatment with 50 mg/kg body weight of CRE could protect sperm during epididymal maturation against oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vyas, Kesari, Lukac, Slama, Roychoudhury and Sisodia.)- Published
- 2023
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28. Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry Estimation of Quercetin-Loaded Nanoemulsion in Rabbit Plasma: In Vivo - In Silico Pharmacokinetic Analysis Using GastroPlus.
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Das SS, Verma PRP, Sekarbabu V, Mohanty S, Pattnaik AK, Ruokolainen J, Kesari KK, and Singh SK
- Abstract
In the present study, we developed and validated a rapid, specific, sensitive, and reproducible liquid chromatography-electrospray ionization tandem mass spectrometry method for quantifying quercetin (QT) in rabbit plasma using hydrochlorothiazide as the internal standard. Animals were orally administered with optimized QT-loaded nanoemulsion (QTNE) and QT suspension (QTS), equivalent to 30 mg/kg, to the test and control group, respectively. The blood samples were collected at pre-determined time points up to 48 h. The linearity range was from 5 to 5000 ng mL
-1 with R2 = 0.995. Further, we analyzed the various pharmacokinetic parameters and established the in vitro - in vivo correlation (IVIVC) of QTNE using GastroPlus software. The method was successfully developed and validated, and when applied for the determination of QT in rabbit plasma, it exhibited an increase in Cmax from 122.56 ng mL-1 (QTS) to 286.51 ng mL-1 (QTNE) (2.34-fold) and AUC0-48 from 976 ng h mL-1 (QTS) to 4249 ng h mL-1 (QTNE) (4.35-fold), indicating improved oral bioavailability QT when administered as QTNE. Statistical analysis revealed that the Loo-Riegelman method (two-compartmental method) best fitted the deconvolution approach ( R2 = 0.998, SEP = 4.537, MAE = 2.759, and AIC = 42.38) for establishing the IVIVC. In conclusion, the established bioanalytical method and IVIVC studies revealed that QTNE is a potential carrier for the effective delivery of QT with enhanced oral bioavailability., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)- Published
- 2023
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29. In Vivo Toxicological Analysis of MnFe 2 O 4 @poly( t BGE-alt-PA) Composite as a Hybrid Nanomaterial for Possible Biomedical Use.
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Kumar R, Bauri S, Sahu S, Chauhan S, Dholpuria S, Ruokolainen J, Kesari KK, Mishra M, and Gupta PK
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- Mice, Animals, Drug Delivery Systems, Tissue Engineering, Drosophila melanogaster genetics, Nanocomposites chemistry
- Abstract
Nanocomposites have significantly contributed to biomedical science due to less aggregation behavior and enhanced physicochemical properties. This study synthesized a MnFe
2 O4 @poly( t BGE-alt-PA) nanocomposite for the first time and physicochemically characterized it. The obtained hybrid nanomaterial was tested in vivo for its toxicological properties before use in drug delivery, tissue engineering fields, and environmental applications. The composite was biocompatible with mouse fibroblast cells and hemocompatible with 2% RBC suspension. This nanocomposite was tested on Drosophila melanogaster due to its small size, well-sequenced genome, and low cost of testing. The larvae's crawling speed and direction were measured after feeding. No abnormal path and altered crawling pattern indicated the nonappearance of abnormal neurological disorder in the larva. The gut organ toxicity was further analyzed using DAPI and DCFH-DA dye to examine the structural anomalies. No apoptosis and necrosis were observed in the gut of the fruit fly. Next, adult flies were examined for phenotypic anomalies after their pupal phases emerged. No defects in the phenotypes, including the eye, wings, abdomen, and bristles, were found in our study. Based on these observations, the MnFe2 O4 @poly( t BGE-alt-PA) composite may be used for various biomedical and environmental applications.- Published
- 2023
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30. Wheat ergot fungus-derived and modified drug for inhibition of intracranial aneurysm rupture due to dysfunction of TLR-4 receptor in Alzheimer's disease.
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Debnath S, Sharma D, Chaudhari SY, Sharma R, Shaikh AA, Buchade RS, Kesari KK, Abdel-Fattah AM, Algahtani M, Mheidat M, Alsaidalani R, Paul T, Sayed AA, and Abdel-Daim MM
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- Humans, Molecular Docking Simulation, Triticum microbiology, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Bromocriptine pharmacology, Claviceps, Intracranial Aneurysm prevention & control, Toll-Like Receptor 4 metabolism
- Abstract
Background: Alzheimer's disease (AD) is a form of dementia that strikes elderly people more frequently than it does younger people. The cognitive skills and memory of Alzheimer's sufferers continue to deteriorate over time. Recent studies have shown that patients with AD have greater amounts of inflammatory markers in their bodies, which suggests that inflammation occurs early on in the progression of the disease. There is a possibility that Aß oligomers and fibrils can be recognised by TLRs, in addition to the microglial receptors CD14, CD36, and CD47. When Aß binds to either CD36 or TLR4, it sets off a chain reaction of inflammatory chemokines and cytokines that ultimately results in neurodegeneration. Diabetes and Alzheimer's disease have both been recently related to TLR4. The activation of TLR4 has been connected to a variety of clinical difficulties that are associated with diabetes, in addition to the internal environment of the body and the microenvironment of the brain. TLR4 inhibitors have been shown in clinical investigations to not only lessen the likelihood of getting sick but also to increase the average longevity., Result: In this work we used molecular docking and molecular dynamics modelling to investigate the effectiveness of FDA-approved antidiabetic plant derived drugs in combating the TLR4 receptor. Molecular docking experiments were used to make a prediction regarding the most important interactions involving 2-Bromoergocryptine Mesylate. With a binding affinity of -8.26 kcal/mol, it stood out from the other candidates as the one with the greatest potential. To verify the interaction pattern that takes place between 2-Bromoergocryptine Mesylate and the TLR4 receptor, a molecular dynamic simulation was run at a time scale of 150 nanoseconds. Because of this, 2-Bromoergocryptine Mesylate was able to make substantial contact with the active site, which led to increased structural stability during the process of the complex's dynamic development., Conclusion: As a result of this, the results of our research may be relevant for future research into the efficacy of 2-bromoergocryptine mesylate as a potential lead treatment for TLR4 receptors in intracranial aneurysm rupture in AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Debnath et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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31. Microbial Inoculants as Plant Biostimulants: A Review on Risk Status.
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Kumari M, Swarupa P, Kesari KK, and Kumar A
- Abstract
Modern agriculture systems are copiously dependent on agrochemicals such as chemical fertilizers and pesticides intended to increase crop production and yield. The indiscriminate use of these chemicals not only affects the growth of plants due to the accumulation of toxic compounds, but also degrades the quality and life-supporting properties of soil. There is a dire need to develop some green approach that can resolve these issues and restore soil fertility and sustainability. The use of plant biostimulants has emerged as an environmentally friendly and acceptable method to increase crop productivity. Biostimulants contain biological substances which may be capable of increasing or stimulating plant growth in an eco-friendly manner. They are mostly biofertilizers that provide nutrients and protect plants from environmental stresses such as drought and salinity. In contrast to the protection of crop products, biostimulants not only act on the plant's vigor but also do not respond to direct actions against pests or diseases. Plant biostimulants improve nutrient mobilization and uptake, tolerance to stress, and thus crop quality when applied to plants directly or in the rhizospheric region. They foster plant growth and development by positively affecting the crop life-cycle starting from seed germination to plant maturity. Legalized application of biostimulants causes no hazardous effects on the environment and primarily provides nutrition to plants. It nurtures the growth of soil microorganisms, which leads to enhanced soil fertility and also improves plant metabolism. Additionally, it may positively influence the exogenous microbes and alter the equilibrium of the microfloral composition of the soil milieu. This review frequently cites the characterization of microbial plant biostimulants that belong to either a high-risk group or are closely related to human pathogens such as Pueudomonas , Klebsiella , Enterobacter , Acinetobacter , etc. These related pathogens cause ailments including septicemia, gastroenteritis, wound infections, inflammation in the respiratory system, meningitis, etc., of varied severity under different conditions of health status such as immunocompromized and comorbidity. Thus it may attract the related concern to review the risk status of biostimulants for their legalized applications in agriculture. This study mainly emphasizes microbial plant biostimulants and their safe application concerns.
- Published
- 2022
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32. Aluminum oxide and zinc oxide induced nanotoxicity in rat brain, heart, and lung.
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Yousef MI, Roychoudhury S, Jafaar KS, Slama P, Kesari KK, and Kamel MA
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- Animals, Rats, Aluminum Oxide toxicity, Antioxidants pharmacology, Acetylcholine pharmacology, Oxidative Stress, Lung metabolism, Brain metabolism, Zinc Oxide toxicity, Nanoparticles toxicity, Metal Nanoparticles toxicity
- Abstract
Nanomaterials or nanoparticles are commonly used in the cosmetics, medicine, and food industries. Many researchers studied the possible side effects of several nanoparticles including aluminum oxide (Al2O3-nps) and zinc oxide nanoparticles (ZnO-nps). Although, there is limited information available on their direct or side effects, especially on the brain, heart, and lung functions. This study aimed to investigate the neurotoxicity, cardiotoxicity, and lung toxicity induced by Al2O3-nps and ZnO-nps or in combination via studying changes in gene expression, alteration in cytokine production, tumor suppressor protein p53, neurotransmitters, oxidative stress, and the histological and morphological changes. Obtained results showed that Al2O3-nps, ZnO-nps and their combination cause an increase in 8-hydroxy-2´-deoxyguanosine (8-OHdG), cytokines, p53, oxidative stress, creatine kinase, norepinephrine, acetylcholine (ACh), and lipid profile. Moreover, significant changes in the gene expression of mitochondrial transcription factor-A (mtTFA) and peroxisome proliferator activator receptor-gamma-coactivator-1alpha (PGC-1alpha) were also noted. On the other hand, a significant decrease in the levels of antioxidant enzymes, total antioxidant capacity (TAC), reduced glutathione (GSH), paraoxonase 1 (PON1), neurotransmitters (dopamine - DA, and serotonin - SER), and the activity of acetylcholine esterase (AChE) in the brain, heart, and lung were found. Additionally, these results were confirmed by histological examinations. The present study revealed that the toxic effects were more when these nanoparticle doses are used in combination. Thus, Al2O3-nps and ZnO-nps may behave as neurotoxic, cardiotoxic, and lung toxic, especially upon exposure to rats in combination.
- Published
- 2022
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33. Estrogen Receptor-α Targeting: PROTACs, SNIPERs, Peptide-PROTACs, Antibody Conjugated PROTACs and SNIPERs.
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Negi A, Kesari KK, and Voisin-Chiret AS
- Abstract
Targeting selective estrogen subtype receptors through typical medicinal chemistry approaches is based on occupancy-driven pharmacology. In occupancy-driven pharmacology, molecules are developed in order to inhibit the protein of interest (POI), and their popularity is based on their virtue of faster kinetics. However, such approaches have intrinsic flaws, such as pico-to-nanomolar range binding affinity and continuous dosage after a time interval for sustained inhibition of POI. These shortcomings were addressed by event-driven pharmacology-based approaches, which degrade the POI rather than inhibit it. One such example is PROTACs (Proteolysis targeting chimeras), which has become one of the highly successful strategies of event-driven pharmacology (pharmacology that does the degradation of POI and diminishes its functions). The selective targeting of estrogen receptor subtypes is always challenging for chemical biologists and medicinal chemists. Specifically, estrogen receptor α (ER-α) is expressed in nearly 70% of breast cancer and commonly overexpressed in ovarian, prostate, colon, and endometrial cancer. Therefore, conventional hormonal therapies are most prescribed to patients with ER + cancers. However, on prolonged use, resistance commonly developed against these therapies, which led to selective estrogen receptor degrader (SERD) becoming the first-line drug for metastatic ER + breast cancer. The SERD success shows that removing cellular ER-α is a promising approach to overcoming endocrine resistance. Depending on the mechanism of degradation of ER-α, various types of strategies of developed.
- Published
- 2022
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34. Re-establishing the comprehension of phytomedicine and nanomedicine in inflammation-mediated cancer signaling.
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Jha NK, Arfin S, Jha SK, Kar R, Dey A, Gundamaraju R, Ashraf GM, Gupta PK, Dhanasekaran S, Abomughaid MM, Das SS, Singh SK, Dua K, Roychoudhury S, Kumar D, Ruokolainen J, Ojha S, and Kesari KK
- Subjects
- Humans, Comprehension, Neoplasm Recurrence, Local, Signal Transduction, Inflammation drug therapy, Phosphatidylinositol 3-Kinases metabolism, Nanomedicine
- Abstract
Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-β/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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35. Clinical Potential of Himalayan Herb Bergenia ligulata : An Evidence-Based Study.
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Roychoudhury S, Das D, Das S, Jha NK, Pal M, Kolesarova A, Kesari KK, Kalita JC, and Slama P
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- Humans, Quercetin, Arbutin, Chlorogenic Acid, Stigmasterol, Eucalyptol, Plant Extracts pharmacology, Plant Extracts therapeutic use, Gallic Acid, Tannins, Phytol, Catechin, Antipyretics, Saxifragaceae, Plants, Medicinal
- Abstract
Herbal products have been used in traditional systems of medicine and by ethnic healers for ages to treat various diseases. Currently, it is estimated that about 80% of people worldwide use herbal traditional medicines against various ailments, partly due to easy accessibility and low cost, and the lower side effects they pose. Bergenia ligulata , a herb ranging from the Himalayas to the foothills, including the north-eastern states of India, has traditionally been used as a remedy against various diseases, most prominently kidney stones. The medicinal properties of B. ligulata have been attributed to bergenin, its most potent bioactive component. Apart from bergenin, the other compounds available in B. ligulata are arbutin, gallic acid, protocatechuic acid, chlorogenic acid, syringic acid, catechin, ferulic acid, afzelechin, paashaanolactone, caryophyllene, 1,8-cineole, β-eudesmol, stigmasterol, β-sitosterol, parasorbic acid, 3-methyl-2-buten-1-ol, phytol, terpinen-4-ol, tannic acid, isovalaric acid, avicularin, quercetin, reynoutrin, and sitoinoside I. This review summarizes various medicinal properties of the herb, along with providing deep insight into its bioactive molecules and their potential roles in the amelioration of human ailments. Additionally, the possible mechanism(s) of action of the herb's anti-urolithiatic, antioxidative, antipyretic, anti-diabetic, anti-inflammatory and hepatoprotective properties are discussed. This comprehensive documentation will help researchers to better understand the medicinal uses of the herb. Further studies on B. ligulata can lead to the discovery of new drug(s) and therapeutics for various ailments.
- Published
- 2022
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36. Comprehensive Analysis of Global Research on Human Varicocele: A Scientometric Approach.
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Agarwal A, Finelli R, Durairajanayagam D, Leisegang K, Henkel R, Salvio G, Aghamajidi A, Sengupta P, Crisóstomo L, Tsioulou PA, Roychoudhury S, Finocchi F, Darbandi M, Mottola F, Darbandi S, Iovine C, Santonastaso M, Zaker H, Kesari KK, Nomanzadeh A, Gugnani N, Rambhatla A, Duran MB, Ceyhan E, Kandil H, Arafa M, Saleh R, Shah R, Ko E, and Boitrelle F
- Abstract
Purpose: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair., Materials and Methods: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software., Results: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature., Conclusions: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele's impact on men's health and male fertility., Competing Interests: The authors have nothing to disclose., (Copyright © 2022 Korean Society for Sexual Medicine and Andrology.)
- Published
- 2022
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37. Polyester nanomedicines targeting inflammatory signaling pathways for cancer therapy.
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Sachi Das S, Singh SK, Verma PRP, Gahtori R, Sibuh BZ, Kesari KK, Jha NK, Dhanasekaran S, Thakur VK, Wong LS, Djearamane S, and Gupta PK
- Subjects
- Drug Delivery Systems, Humans, Inflammation drug therapy, Nanomedicine, Polyesters, Signal Transduction, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Neoplasms pathology
- Abstract
The growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-β), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving the physicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer., Competing Interests: Conflict of interest statement The authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2022
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38. A Comparative Cross-Platform Analysis to Identify Potential Biomarker Genes for Evaluation of Teratozoospermia and Azoospermia.
- Author
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Das S, Guha P, Nath M, Das S, Sen S, Sahu J, Kopanska M, Dutta S, Jamal QMS, Kesari KK, Sengupta P, Slama P, and Roychoudhury S
- Subjects
- Male, Humans, Semen metabolism, Biomarkers, RNA, Teratozoospermia genetics, Teratozoospermia metabolism, Azoospermia diagnosis, Azoospermia genetics, Infertility, Male genetics
- Abstract
Male infertility is a global public health concern. Teratozoospermia is a qualitative anomaly of spermatozoa morphology, contributing significantly to male infertility, whereas azoospermia is the complete absence of spermatozoa in the ejaculate. Thus, there is a serious need for unveiling the common origin and/or connection between both of these diseases, if any. This study aims to identify common potential biomarker genes of these two diseases via an in silico approach using a meta-analysis of microarray data. In this study, a differential expression analysis of genes was performed on four publicly available RNA microarray datasets, two each from teratozoospermia (GSE6872 and GSE6967) and azoospermia (GSE145467 and GSE25518). From the analysis, 118 DEGs were found to be common to teratozoospermia and azoospermia, and, interestingly, sperm autoantigenic protein 17 ( SPA17 ) was found to possess the highest fold change value among all the DEGs (9.471), while coiled-coil domain-containing 90B ( CCDC90B ) and coiled-coil domain-containing 91 ( CCDC91 ) genes were found to be common among three of analyses, i.e., Network Analyst, ExAtlas, and GEO2R. This observation indicates that SPA17, CCDC90B, and CCDC91 genes might have significant roles to play as potential biomarkers for teratozoospermia and azoospermia. Thus, our study opens a new window of research in this area and can provide an important theoretical basis for the diagnosis and treatment of both these diseases.
- Published
- 2022
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39. Epigenetic factors in breast cancer therapy.
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Mathur R, Jha NK, Saini G, Jha SK, Shukla SP, Filipejová Z, Kesari KK, Iqbal D, Nand P, Upadhye VJ, Jha AK, Roychoudhury S, and Slama P
- Abstract
Epigenetic modifications are inherited differences in cellular phenotypes, such as cell gene expression alterations, that occur during somatic cell divisions (also, in rare circumstances, in germ line transmission), but no alterations to the DNA sequence are involved. Histone alterations, polycomb/trithorax associated proteins, short non-coding or short RNAs, long non-coding RNAs (lncRNAs), & DNA methylation are just a few biological processes involved in epigenetic events. These various modifications are intricately linked. The transcriptional potential of genes is closely conditioned by epigenetic control, which is crucial in normal growth and development. Epigenetic mechanisms transmit genomic adaptation to an environment, resulting in a specific phenotype. The purpose of this systematic review is to glance at the roles of Estrogen signalling, polycomb/trithorax associated proteins, DNA methylation in breast cancer progression, as well as epigenetic mechanisms in breast cancer therapy, with an emphasis on functionality, regulatory factors, therapeutic value, and future challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mathur, Jha, Saini, Jha, Shukla, Filipejová, Kesari, Iqbal, Nand, Upadhye, Jha, Roychoudhury and Slama.)
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- 2022
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40. Unravelling the molecular mechanism of mutagenic factors impacting human health.
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Goyal K, Goel H, Baranwal P, Dixit A, Khan F, Jha NK, Kesari KK, Pandey P, Pandey A, Benjamin M, Maurya A, Yadav V, Sinh RS, Tanwar P, Upadhyay TK, and Mittan S
- Subjects
- Animals, Carcinogenesis, DNA Damage, Humans, Mutagenesis, Mutagenicity Tests, Mutagens chemistry, Mutagens toxicity, Polycyclic Aromatic Hydrocarbons toxicity
- Abstract
Environmental mutagens are chemical and physical substances in the environment that has a potential to induce a wide range of mutations and generate multiple physiological, biochemical, and genetic modifications in humans. Most mutagens are having genotoxic effects on the following generation through germ cells. The influence of germinal mutations on health will be determined by their frequency, nature, and the mechanisms that keep a specific mutation in the population. Early prenatal lethal mutations have less public health consequences than genetic illnesses linked with long-term medical and social difficulties. Physical and chemical mutagens are common mutagens found in the environment. These two environmental mutagens have been associated with multiple neurological disorders and carcinogenesis in humans. Thus in this study, we aim to unravel the molecular mechanism of physical mutagens (UV rays, X-rays, gamma rays), chemical mutagens (dimethyl sulfate (DMS), bisphenol A (BPA), polycyclic aromatic hydrocarbons (PAHs), 5-chlorocytosine (5ClC)), and several heavy metals (Ar, Pb, Al, Hg, Cd, Cr) implicated in DNA damage, carcinogenesis, chromosomal abnormalities, and oxidative stress which leads to multiple disorders and impacting human health. Biological tests for mutagen detection are crucial; therefore, we also discuss several approaches (Ames test and Mutatox test) to estimate mutagenic factors in the environment. The potential risks of environmental mutagens impacting humans require a deeper basic knowledge of human genetics as well as ongoing research on humans, animals, and their tissues and fluids., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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41. CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics.
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Bhardwaj S, Kesari KK, Rachamalla M, Mani S, Ashraf GM, Jha SK, Kumar P, Ambasta RK, Dureja H, Devkota HP, Gupta G, Chellappan DK, Singh SK, Dua K, Ruokolainen J, Kamal MA, Ojha S, and Jha NK
- Subjects
- Amyloid beta-Peptides genetics, Amyloid beta-Protein Precursor genetics, CRISPR-Cas Systems genetics, Humans, Alzheimer Disease genetics, Alzheimer Disease therapy, Gene Editing
- Abstract
Background: Alzheimer's disease (AD) is an insidious, irreversible, and progressive neurodegenerative health condition manifesting as cognitive deficits and amyloid beta (Aβ) plaques and neurofibrillary tangles. Approximately 50 million individuals are affected by AD, and the number is rapidly increasing globally. This review explores the role of CRISPR/Cas9 gene editing in the management of AD and its clinical manifestations., Aim of Review: This review aims to provide a deep insight into the recent progress in CRISPR/Cas9-mediated genome editing and its use against neurodegenerative disorders, specifically AD. However, we have referred to its use against parkinsons's disease (PD), Huntington's disease (HD), and other human diseases, as is one of the most promising and emerging technologies for disease treatment., Key Scientific Concepts of Review: The pathophysiology of AD is known to be linked with gene mutations, that is, presenilin (PSEN) and amyloid beta precursor protein (APP). However, clinical trials focused at the genetic level could not meet the desired efficiency. The CRISPR/Cas9 genome editing tool is one of the most powerful technologies for correcting inconsistent genetic signatures and now extensively used for AD management. It has significant potential for the correction of undesired gene mutations associated with AD. This technology has allowed the development of empirical AD models, therapeutic lines, and diagnostic approaches for better understanding the nervous system, from in vitro to in vivo models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Production and hosting by Elsevier B.V.)
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- 2022
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42. Mutagenic factors in the environment impacting human and animal health.
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Roychoudhury S, Jha NK, Ruokolainen J, and Kesari KK
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- Animals, Humans, Mutagenesis, Mutagenicity Tests, Environment, Mutagens
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- 2022
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43. Cellular landscaping of cisplatin resistance in cervical cancer.
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Bhattacharjee R, Dey T, Kumar L, Kar S, Sarkar R, Ghorai M, Malik S, Jha NK, Vellingiri B, Kesari KK, Pérez de la Lastra JM, and Dey A
- Subjects
- Cell Line, Tumor, Cisplatin pharmacology, Cisplatin therapeutic use, Drug Resistance, Neoplasm, Female, HeLa Cells, Humans, Papillomaviridae, Tumor Microenvironment, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Uterine Cervical Neoplasms drug therapy, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms pathology
- Abstract
Cervical cancer (CC) caused by human papillomavirus (HPV) is one of the largest causes of malignancies in women worldwide. Cisplatin is one of the widely used drugs for the treatment of CC is rendered ineffective owing to drug resistance. This review highlights the cause of resistance and the mechanism of cisplatin resistance cells in CC to develop therapeutic ventures and strategies that could be utilized to overcome the aforementioned issue. These strategies would include the application of nanocarries, miRNA, CRIPSR/Cas system, and chemotherapeutics in synergy with cisplatin to not only overcome the issues of drug resistance but also enhance its anti-cancer efficiency. Moreover, we have also discussed the signaling network of cisplatin resistance cells in CC that would provide insights to develop therapeutic target sites and inhibitors. Furthermore, we have discussed the role of CC metabolism on cisplatin resistance cells and the physical and biological factors affecting the tumor microenvironments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2022
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44. Structural and Functional Characterization at the Molecular Level of the MATE Gene Family in Wheat in Silico.
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Debnath S, Mohanta D, Perveen K, Husain FM, Kesari KK, Ashraf MS, Mukerjee N, and Rahin SA
- Abstract
A series of multidrug extransporters known as the multidrug and potentially toxic extrusion (MATE) genes are found in all living things and are crucial for the removal of heavy metal ions, metalloids, exogenous xenobiotics, endogenous secondary metabolites, and other toxic substances from the cells. However, there has only been a small amount of them in silico analysis of the MATE family of genes in plant species. In the current study, the MATE gene family was characterized in silico where two families and seven subfamilies based on their evolutionary relationships were proposed. Plant breeders may use TraesCS1D02G030400, TraesCS4B02G244400, and TraesCS1A02G029900 genes for marker-assisted or transgenic breeding to develop novel cultivars since these genes have been hypothesized from protein-protein interaction study to play a critical role in the transport of toxic chemicals across cells. The exon number varies from 01 to 14. One exon has TraesCS1A02G188100, TraesCS5B02G562500, TraesCS6A02G256400, and TraesCS6D02G384300 genes, while 14 exons have only two genes that are TraesCS6A02G418800 and TraesCS6D02G407900. Biological stress (infestations of disease) affects the expression of most of the MATE genes, with the gene TraesCS5D02G355500 having the highest expression level in the wheat expression browser tool. Using the Grain interpretation search engine tool, it is found that the vast bulk of MATE genes are voiced throughout biotic environmental stresses caused by disease pests, with the genotype TraesCS5B02G326600.1 from family 1 exhibiting the greatest level of expression throughout Fusarium head blight infection by Fusarium graminearum after 4 days of infection. The researchers constructed 39 ternary plots, each with a distinct degree of expression under biotic and abiotic stress settings, and observed that 44% of the triplets have imbalanced outputs (extreme values) due to their higher tissue specificity and increased intensity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Sandip Debnath et al.)
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- 2022
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45. Chitosan Nanoparticle Encapsulation of Antibacterial Essential Oils.
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Negi A and Kesari KK
- Abstract
Chitosan is the most suitable encapsulation polymer because of its natural abundance, biodegradability, and surface functional groups in the form of free NH
2 groups. The presence of NH2 groups allows for the facile grafting of functionalized molecules onto the chitosan surface, resulting in multifunctional materialistic applications. Quaternization of chitosan's free amino is one of the typical chemical modifications commonly achieved under acidic conditions. This quaternization improves its ionic character, making it ready for ionic-ionic surface modification. Although the cationic nature of chitosan alone exhibits antibacterial activity because of its interaction with negatively-charged bacterial membranes, the nanoscale size of chitosan further amplifies its antibiofilm activity. Additionally, the researcher used chitosan nanoparticles as polymeric materials to encapsulate antibiofilm agents (such as antibiotics and natural phytochemicals), serving as an excellent strategy to combat biofilm-based secondary infections. This paper provided a summary of available carbohydrate-based biopolymers as antibiofilm materials. Furthermore, the paper focuses on chitosan nanoparticle-based encapsulation of basil essential oil ( Ocimum basilicum ), mandarin essential oil ( Citrus reticulata ), Carum copticum essential oil ("Ajwain"), dill plant seed essential oil ( Anethum graveolens ), peppermint oil ( Mentha piperita ), green tea oil ( Camellia sinensis ), cardamom essential oil, clove essential oil ( Eugenia caryophyllata ), cumin seed essential oil ( Cuminum cyminum ), lemongrass essential oil ( Cymbopogon commutatus ), summer savory essential oil ( Satureja hortensis ), thyme essential oil, cinnamomum essential oil ( Cinnamomum zeylanicum ), and nettle essential oil ( Urtica dioica ). Additionally, chitosan nanoparticles are used for the encapsulation of the major essential components carvacrol and cinnamaldehyde, the encapsulation of an oil-in-water nanoemulsion of eucalyptus oil ( Eucalyptus globulus ), the encapsulation of a mandarin essential oil nanoemulsion, and the electrospinning nanofiber of collagen hydrolysate-chitosan with lemon balm ( Melissa officinalis ) and dill ( Anethum graveolens ) essential oil.- Published
- 2022
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46. Principal Component and Path Analysis for Trait Selection Based on the Assessment of Diverse Lentil Populations Developed by Gamma-Irradiated Physical Mutation.
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Debnath S, Sarkar A, Perveen K, Bukhari NA, Kesari KK, Verma A, Chakraborty NR, and Tesema M
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- Gamma Rays, Mutation genetics, Phenotype, Plant Breeding methods, Lens Plant chemistry, Lens Plant genetics
- Abstract
Lentil is a notable legume crop valued for its high protein, vitamin, mineral, and amino acid (lysine and tryptophan) content. This crop has a narrow genetic base due to the formation of gene pool barriers during interspecific hybridization within and across species. Mutagenesis may be seen as a novel and alternative breeding technique for the production of new diversity. For the identification of new alleles, the creation of mutants followed by selection in subsequent generations would be necessary. Induction of mutation in lentil cv. Moitree by gamma rays therefore produced high variation for the majority of quantitative measures examined. Henceforth, principal component analysis (PCA) and path coefficient analysis were conducted to identify and exclude redundant mutant genotypes with similar traits as the success of breeding is dependent on understanding the relationship between morpho-agronomic traits and seed yield. As shown by the findings of this research, the total quantity of pods per mutant plant should be given considerable priority. The identified mutant genotypes, such as lines 24, 43, 28, 33, and 10, may be used as parents in future breeding or released directly following trials., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Sandip Debnath et al.)
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- 2022
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47. Food-Grade Quercetin-Loaded Nanoemulsion Ameliorates Effects Associated with Parkinson's Disease and Cancer: Studies Employing a Transgenic C. elegans Model and Human Cancer Cell Lines.
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Das SS, Sarkar A, Chabattula SC, Verma PRP, Nazir A, Gupta PK, Ruokolainen J, Kesari KK, and Singh SK
- Abstract
A nanosized food-grade quercetin-loaded nanoemulsion (QNE) system comprising capmul MCM NF (oil) and cremophor RH 40 (surfactant) was developed using a high-speed homogenization technique. The developed QNE was studied for its significant neuroprotective (anti-Parkinsonism) and cytotoxicity (anticancer) effects against Caenorhabditis elegans (C. elegans) strains and human cancer cells, respectively. HR-TEM studies revealed that the QNE was spherical with a mean globule size of ~50 nm. Selected area electron diffraction (SAED) studies results demonstrated that QNE was amorphous. In vivo results show that QNE potentially reduced the α-Syn aggregation, increased mitochondrial and fat content, and improved the lifespan in transgenic C. elegans strain NL5901. QNE significantly downregulated the reactive oxygen species (ROS) levels in wild-type C. elegans strain N2. In vitro results of the MTT assay show that QNE significantly exhibited chemotherapeutic effects in all treated human cancer cells in an order of cytotoxicity: HeLa cells > A549 cells > MIA PaCa-2 cells, based on the IC50 values at 24 h. Conclusively, the QNE showed improved solubility, targetability, and neuroprotective effects against the PD-induced C. elegans model, and also cytotoxicity against human cancer cells and could be potentially used as an anti-Parkinson’s or anticancer agent.
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- 2022
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48. Insights into the cytoprotective potential of Bergenia ligulata against oxalate-induced oxidative stress and epithelial-mesenchymal transition (EMT) via TGFβ1/p38MAPK pathway in human renal epithelial cells.
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Singh A, Tandon S, Kumar D, Kaur T, Kesari KK, and Tandon C
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- Epithelial Cells metabolism, Female, Humans, Inflammation, Male, Oxalates metabolism, Oxidative Stress, Plant Extracts pharmacology, Plant Extracts therapeutic use, Transforming Growth Factor beta1 metabolism, Transforming Growth Factor beta1 pharmacology, p38 Mitogen-Activated Protein Kinases metabolism, p38 Mitogen-Activated Protein Kinases pharmacology, Epithelial-Mesenchymal Transition, Kidney Calculi chemically induced, Kidney Calculi drug therapy, Kidney Calculi prevention & control
- Abstract
Oxalate exposure to human renal epithelial cells triggers a vicious cycle of oxidative stress leading to cellular injury and deposition of calcium oxalate crystals on the injured cells. This results in further oxidative damage causing inflammation and loss of cell-cell adhesion factors, ultimately leading to irreparable kidney damage. However, these events can be attenuated or prevented by plants rich in antioxidants used in the traditional system of medicine for treatment of kidney stones. To delineate the mechanism by which Bergenia ligulata extract exerts its cytoprotective role in oxalate-induced injury we designed this study. Our results revealed that oxalate-injured HK2 cells cotreated with ethanolic extract of Bergenia ligulata displayed increased viability, reduced oxidative stress due to lowered production of intracellular reactive oxygen species (ROS) and decreased apoptosis. We also observed lowered markers of inflammation, along with increased expression of epithelial marker E-cadherin and decreased expression of mesenchymal markers Vimentin, F-actin, Transforming growth factor beta 1 (TGF-β1) and EMT-related proteins in renal tubular epithelial cells through immunocytochemistry, real-time PCR and western blotting. Our findings collectively suggest that by reducing oxidative stress, modulating crystal structure and preventing crystal-cell adhesion, B. ligulata inhibits the EMT pathway by downregulating the various mediators and thereby exerts its cytoprotective effect., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2022
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49. Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies.
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Bhattacharjee R, Das SS, Biswal SS, Nath A, Das D, Basu A, Malik S, Kumar L, Kar S, Singh SK, Upadhye VJ, Iqbal D, Almojam S, Roychoudhury S, Ojha S, Ruokolainen J, Jha NK, and Kesari KK
- Subjects
- Female, Human papillomavirus 16, Humans, Papillomavirus E7 Proteins, Phosphatidylinositol 3-Kinases, Oncogene Proteins, Viral genetics, Oncogene Proteins, Viral metabolism, Papillomavirus Infections, Uterine Cervical Neoplasms etiology, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms therapy
- Abstract
Purpose: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented., Methods: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling., Results: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only., Conclusion: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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50. Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer's Disease.
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Jana A, Bhattacharjee A, Das SS, Srivastava A, Choudhury A, Bhattacharjee R, De S, Perveen A, Iqbal D, Gupta PK, Jha SK, Ojha S, Singh SK, Ruokolainen J, Jha NK, Kesari KK, and Ashraf GM
- Subjects
- Aged, Brain metabolism, Humans, Neurons metabolism, Oxidative Stress, Alzheimer Disease pathology
- Abstract
Alzheimer's disease (AD) is one of the most complex progressive neurological disorders involving degeneration of neuronal connections in brain cells leading to cell death. AD is predominantly detected among elder people (> 65 years), mostly diagnosed with the symptoms of memory loss and cognitive dysfunctions. The multifarious pathogenesis of AD comprises the accumulation of pathogenic proteins, decreased neurotransmission, oxidative stress, and neuroinflammation. The conventional therapeutic approaches are limited to symptomatic benefits and are ineffective against disease progression. In recent years, researchers have shown immense interest in the designing and fabrication of various novel therapeutics comprised of naturally isolated hybrid molecules. Hybrid therapeutic compounds are developed from the combination of pharmacophores isolated from bioactive moieties which specifically target and block various AD-associated pathogenic pathways. The method of designing hybrid molecules has numerous advantages over conventional multitarget drug development methods. In comparison to in silico high throughput screening, hybrid molecules generate quicker results and are also less expensive than fragment-based drug development. Designing hybrid-multitargeted therapeutic compounds is thus a prospective approach in developing an effective treatment for AD. Nevertheless, several issues must be addressed, and additional researches should be conducted to develop hybrid therapeutic compounds for clinical usage while keeping other off-target adverse effects in mind. In this review, we have summarized the recent progress on synthesis of hybrid compounds, their molecular mechanism, and therapeutic potential in AD. Using synoptic tables, figures, and schemes, the review presents therapeutic promise and potential for the development of many disease-modifying hybrids into next-generation medicines for AD., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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