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User-driven health care: answering multidimensional information needs in individual patients utilizing post-EBM approaches: an operational model

Biswas R, Maniam J, Lee EW, Gopal P, Umakanth S, Dahiya S, et al.

J Eval Clin Pract, 2008 Oct;14(5):750-60.
PMID: 19018906 DOI: 10.1111/j.1365-2753.2008.00997.x

The hypothesis in the conceptual model was that a user-driven innovation in presently available information and communication technology infrastructure would be able to meet patient and health professional users information needs and help them attain better health outcomes. An operational model was created to plan a trial on a sample diabetic population utilizing a randomized control trial design, assigning one randomly selected group of diabetics to receive electronic information intervention and analyse if it would improve their health outcomes in comparison with a matched diabetic population who would only receive regular medical intervention. Diabetes was chosen for this particular trial, as it is a major chronic illness in Malaysia as elsewhere in the world. It is in essence a position paper for how the study concept should be organized to stimulate wider discussion prior to beginning the study.
Natural cyclic polypeptides as vital phytochemical constituents from seeds of selected medicinal plants

Dahiya R, Dahiya S, Shrivastava J, Fuloria NK, Gautam H, Mourya R, et al.

Arch Pharm (Weinheim), 2021 Feb 01.
PMID: 33522644 DOI: 10.1002/ardp.202000446

Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process. The current study covers the important structural features, structure-activity relationship, synthesis methods, and bioproperties of plant seeds-originated bioactive peptides from Vaccaria segetalis, Linum usitatissimum, and Goniothalamus leiocarpus, which may prove vital for the development of novel therapeutics based on a peptide skeleton.
Natural Bridged Bicyclic Peptide Macrobiomolecules from Celosia argentea and Amanita phalloides

Dahiya S, Dahiya R, Fuloria NK, Mourya R, Dahiya S, Fuloria S, et al.

Mini Rev Med Chem, 2022 Jan 13.
PMID: 35049431 DOI: 10.2174/1389557522666220113122117

Bridged peptide macrobicycles (BPMs) from natural resources belong to types of compounds that are not investigated fully in terms of their formation, pharmacological potential and stereo-chemical properties. This division of biologically active congeners with multiple circular rings, has merits over other varieties of peptide molecules. BPMs form one of the most hopeful grounds for establishment of drugs because of their close resemblance and biocompatibility to proteins, and these bio-actives are debated as feasible realistic tools in diverse biomedical applications. Despite huge potential, poor metabolic stability and cell permeability limit the therapeutic success of macrocyclic peptides. In this review, we have comprehensively explored major bicyclic peptides sourced from plants and mushrooms including βs-leucyl-tryptophano-histidine bridged and tryptophano-cysteine bridged peptide macrobicycles. The unique structural features, structure activity relationship, synthetic routes, bioproperties and therapeutic potential of the natural BPMs are also discussed.
Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension

Singh Y, Samuel VP, Dahiya S, Gupta G, Gillhotra R, Mishra A, et al.

Biotechnol Appl Biochem, 2019 Sep;66(5):715-719.
PMID: 31314127 DOI: 10.1002/bab.1799

Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.
Fulltext Mesenchymal Stem Cell-Derived Extracellular Vesicles: Regenerative Potential and Challenges

Fuloria S, Subramaniyan V, Dahiya R, Dahiya S, Sudhakar K, Kumari U, et al.

Biology (Basel), 2021 Feb 25;10(3).
PMID: 33668707 DOI: 10.3390/biology10030172

Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.
A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia

Sah SK, Samuel VP, Dahiya S, Singh Y, Gilhotra RM, Gupta G, et al.

Chem Biol Interact, 2019 Jun 01;306:117-122.
PMID: 31004596 DOI: 10.1016/j.cbi.2019.04.022

Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.
Fulltext Comparative Analysis of Erosive Wear Behaviour of Epoxy, Polyester and Vinyl Esters Based Thermosetting Polymer Composites for Human Prosthetic Applications Using Taguchi Design

Khare JM, Dahiya S, Gangil B, Ranakoti L, Sharma S, Huzaifah MRM, et al.

Polymers (Basel), 2021 Oct 19;13(20).
PMID: 34685366 DOI: 10.3390/polym13203607

In polymer composites, synthetic fibers are primarily used as a chief reinforcing material, with a wide range of applications, and are therefore essential to study. In the present work, we carried out the erosive wear of natural and synthetic fiber-based polymer composites. Glass fiber with jute and Grewia optiva fiber was reinforced in three different polymer resins: epoxy, vinyl ester and polyester. The hand lay-up method was used for the fabrication of composites. L16 orthogonal array of Taguchi method used to identify the most significant parameters (impact velocity, fiber content, and impingement angle) in the analysis of erosive wear. ANOVA analysis revealed that the most influential parameter was in the erosive wear analysis was impact velocity followed by fiber content and impingement angle. It was also observed that polyester-based composites exhibited the highest erosive wear followed by vinyl ester-based composites, and epoxy-based composites showed the lowest erosive wear. From the present study, it may be attributed that the low hardness of the polyester resulting in low resistance against the impact of erodent particles. The SEM analysis furthermore illustrates the mechanism took place during the wear examination of all three types of composites at highest fiber loading. A thorough assessment uncovers brittle fractures in certain regions, implying that a marginal amount of impact forces was also acting on the fabricated samples. The developed fiber-reinforced polymer sandwich composite materials possess excellent biocompatibility, desirable promising properties for prosthetic, orthopaedic, and bone-fracture implant uses.
Natural Thiazoline-Based Cyclodepsipeptides from Marine Cyanobacteria: Chemistry, Bioefficiency and Clinical Aspects

Dahiya R, Dahiya S, Fuloria NK, Jankie S, Agarwal A, Davis V, et al.

Curr Med Chem, 2021;28(38):7887-7909.
PMID: 34042024 DOI: 10.2174/0929867328666210526095436

BACKGROUND: Peptides and peptide-based therapeutics are biomolecules that demarcate a significant chemical space to bridge small molecules with biological therapeutics, such as antibodies, recombinant proteins, and protein domains.
INTRODUCTION: Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived thiazoline-based polypeptides (CTBCs), exhibit a wide array of pharmacological activities due to their unique structural features and interesting bioactions, which furnish them as promising leads for drug discovery.
METHODS: In the present study, we comprehensively review the natural sources, distinguishing chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities counting the mode of actions for biological portrayals which render CTBCs as indispensable sources for emergence of prospective peptide-based therapeutics. In this milieu, metal organic frameworks and their biomedical applications are also briefly discussed. To boot, the challenges, approaches, and clinical status of peptide-based therapeutics are conferred.
RESULTS: Based on these analyses, CTBCs can be appraised as ideal drug targets that have always remained a challenge for traditional small molecules, like those involved in protein- protein interactions or to be developed as potential cancer-targeting nanomaterials. Cyclization-induced reduced conformational freedom of these cyclooligopeptides contribute to improved metabolic stability and binding affinity to their molecular targets. Clinical success of several cyclic peptides provokes the large library-screening and synthesis of natural product-like cyclic peptides to address the unmet medical needs.
CONCLUSION: CTBCs can be considered as the most promising lead compounds for drug discovery. Adopting the amalgamation of advanced biological and biopharmaceutical strategies might endure these cyclopeptides to be prospective biomolecules for futuristic therapeutic applications in the coming times.
Fulltext Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects

Dahiya R, Dahiya S, Fuloria NK, Kumar S, Mourya R, Chennupati SV, et al.

Mar Drugs, 2020 Jun 24;18(6).
PMID: 32599909 DOI: 10.3390/md18060329

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide-peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.