Flavonoid-Rich Trianthema decandra Ameliorates Cognitive Dysfunction in the Hyperglycemic Rats.

The present study was aimed at the evaluation of neuroprotective ability of methanolic extract of Trianthema decandra (METD) against hyperglycemia-related cognitive impairment in rats. The extract of T. decandra was standardized by TLC and HPTLC methods. To verify the identity and purity of isolated compounds, they were segregated and characterized using various techniques, including UV-visible spectrophotometry, FT-IR, H-NMR, and Mass spectroscopy. α-Amylase and α-glucosidase inhibition property of the extracts were assessed in-vitro. The screening of the neuroprotective effects of METD in hyperglycemic rats was done utilizing Morri's water (MWM) and elevated plus maze (EPM) model, as well as acetylcholinesterase (AChE) activity. The extracts of Trianthema decandra and its chemical constituents, namely quercetin and phytol, demonstrated a significant protective effect on enzymes like α-amylase and α-glucosidase. Methanol and hydroalcoholic extracts have shown the strongest inhibitory activity followed by chloroform extract. Quercetin and phytol were associated with the methanolic and chloroform extracts which were identified using TLC and HPTLC techniques. During the thirty days of the study, the induction of diabetes in the rats exhibited persistent hyperglycemia, hyperlipidemia, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Regimen of METD (200 and 400 mg/kg) in the diabetic rats reduced the glucose levels in blood, lipid, and liver profile and showed positive results on Morri's water and elevated plus maze tasks. During the investigation, it was determined that Trianthema decandra extracts and the chemical constituent's quercetin and phytol in it had anti-diabetic and neuroprotective activities.

Analysing the influence of ground granulated blast furnace slag and steel fibre on RC beams flexural behaviour.

This study examines the effect of Ground Granulated Blast Furnace Slag (GGBS) and steel fibers on the flexural behaviour of RC beams under monotonic loading. Various percentages of GGBS were used to substitute cement, namely 0%, 20%, 40%, 60%, and 80% and fibers were added to the concrete mix as 0%, 0.5%, 1%, and 1.5% of the volume of concrete. The load-deflection behaviour of GGBS-incorporated RC beams with fibers was compared with the control RC beam. Beams were tested under load control for 28 days and 180 days. The ultimate load of the GGBS-incorporated RC beam up to 40% cement replacement was found to higher than that of the control beam. The strength of concrete is reduced by 28% and 19% when cement was partially replaced by 80% of GGBS at 28 and 180 days, respectively, compared to control concrete without fibres. Further, the analytical load-deflection response of GGBS-incorporated RC beams was determined by using several codes of practice, namely, ACI 318-11(2011), CSA A23.3-04 (2004), EC-04 (2004), and IS 456 (2000). The Codal provisions were primarily based on the effective moment of inertia, Young's modulus, and modulus of rupture, stiffness, and cracking. Average load-deflection plots obtained from experiments were compared with the computed load-deflection of analytical studies. It was found that the analytically predicted load-deflection behaviour is comparable with the corresponding average experimental load-deflection response. Moment curvature relations were also developed for RC beams.

Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies.

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin-angiotensin-aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer.

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be -10.7, -8.5, -6.6, -8.7, -8.6, -24.5, -6.7, -8.3, and -7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.

Long non-coding RNAs: controversial roles in drug resistance of solid tumors mediated by autophagy.

Current genome-wide studies have indicated that a great number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and appeared as crucial regulators in a variety of cellular processes. Many studies have displayed a significant function of lncRNAs in the regulation of autophagy. Autophagy is a macromolecular procedure in cells in which intracellular substrates and damaged organelles are broken down and recycled to relieve cell stress resulting from nutritional deprivation, irradiation, hypoxia, and cytotoxic agents. Autophagy can be a double-edged sword and play either a protective or a damaging role in cells depending on its activation status and other cellular situations, and its dysregulation is related to tumorigenesis in various solid tumors. Autophagy induced by various therapies has been shown as a unique mechanism of resistance to anti-cancer drugs. Growing evidence is showing the important role of lncRNAs in modulating drug resistance via the regulation of autophagy in a variety of cancers. The role of lncRNAs in drug resistance of cancers is controversial; they may promote or suppress drug resistance via either activation or inhibition of autophagy. Mechanisms by which lncRNAs regulate autophagy to affect drug resistance are different, mainly mediated by the negative regulation of micro RNAs. In this review, we summarize recent studies that investigated the role of lncRNAs/autophagy axis in drug resistance of different types of solid tumors.

QbD driven targeted pulmonary delivery of dexamethasone-loaded chitosan microspheres: Biodistribution and pharmacokinetic study.

Inhaling drugs, on the other hand, is limited mainly by the natural mechanisms of the respiratory system, which push drug particles out of the lungs or make them inefficient once they are there. Because of this, many ways have been found to work around the problems with drug transport through the lungs. Researchers have made polymeric microparticles (MP) and nanoparticles as a possible way to get drugs into the lungs. They showed that the drug could be trapped in large amounts and retained in the lungs for a long time, with as little contact as possible with the bloodstream. MP were formulated in this study to get dexamethasone (DMC) into the pulmonary area. The Box-Behnken design optimized microspheres preparation to meet the pulmonary delivery prerequisites. Optimized formulation was figured out based on the desirability approach. The mass median aerodynamic diameter (MMAD) of the optimized formula (O-DMC-MP) was 8.46 ± 1.45 µm, and the fine particle fraction (FPF) was 77.69 ± 1.26%. This showed that it made suitable drug delivery system, which could make it possible for MP to settle deeply in the lung space after being breathed in. With the first burst of drug release, it was seen that drug release could last up to 16 h. Also, there was no clear sign that the optimized formulation was toxic to the alveoli basal epithelial cells in the lungs, as supported by cytotoxic studies in HUVEC, A549, and H1299 cell lines. Most importantly, loading DMC inside MP cuts the amount of drug into the bloodstream compared to plain DMC, as evident from biodistribution studies. Stability tests have shown that the product can stay the same over time at both the storage conditions. Using chitosan DMC-MP can be a better therapeutic formulation to treat acute respiratory distress syndrome (ARDS).

A comprehensive insight into the role of small nucleolar RNAs (snoRNAs) and SNHGs in human cancers.

Long non-coding RNAs (lncRNAs), which comprise most non-coding RNAs (ncRNAs), have recently become a focus of cancer research. How many functional ncRNAs exist is still a matter of debate. Although insufficient evidence supports that most lncRNAs function as transcriptional by-products, it is widely known that an increasing number of lncRNAs play essential roles in cells. Small nucleolar RNAs (snoRNAs), 60-300 nucleotides in length, have been better studied than long non-coding RNAs (lncRNAs) and are predominantly present in the nucleolus. Most snoRNAs are encoded in introns of protein- and non-protein-coding genes called small nucleolar RNA host genes (SNHGs). In this article, we explore the biology and characteristics of SNHGs and their role in developing human malignancies. In addition, we provide an update on the ability of these snoRNAs to serve as prognostic and diagnostic variables in various forms of cancer.

Fluorescent-Nanoparticle-Impregnated Nanocomposite Polymeric Gels for Biosensing and Drug Delivery Applications.

Nanocomposite polymeric gels infused with fluorescent nanoparticles have surfaced as a propitious category of substances for biomedical purposes owing to their exceptional characteristics. The aforementioned materials possess a blend of desirable characteristics, including biocompatibility, biodegradability, drug encapsulation, controlled release capabilities, and optical properties that are conducive to imaging and tracking. This paper presents a comprehensive analysis of the synthesis and characterization of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels, as well as their biomedical applications, such as drug delivery, imaging, and tissue engineering. In this discourse, we deliberate upon the merits and obstacles linked to these substances, encompassing biocompatibility, drug encapsulation, optical characteristics, and scalability. The present study aims to provide an overall evaluation of the potential of fluorescent-nanoparticle-impregnated nanocomposite polymeric gels for biomedical applications. Additionally, emerging trends and future directions for research in this area are highlighted.

LncRNA PVT1: as a therapeutic target for breast cancer.

A significant number of women are identified with breast cancer (BC) every year, making it among the most prevalent malignancies and one of the leading causes of mortality globally. Despite significant progress in understanding BC pathogenesis and treatment options, there is still a need to identify new therapeutic targets and develop more effective treatments. LncRNAs have been discovered as biomarkers and a promising target for various cancers, including BC. PVT1 is a particular one of these lncRNAs, and research has indicated that it has a significant impact on the appearance and progression of BC.PVT1 is an attractive therapeutic target for BC due to its role in promoting cancer cell growth, metastasis and invasion. In addition to its potential as a treatment strategy, PVT1 may also have diagnostic value in BC. In this article, we will discuss targeting PVT1 as a treatment strategy for BC.

Carotenoids: Role in Neurodegenerative Diseases Remediation.

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as "CTs", are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.