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Prebiotics are nondigestible components that comprise short-chain carbohydrates, primarily oligosaccharides, which are converted into beneficial compounds by probiotics. Various plant substances with prebiotic properties provide substantial health benefits and are used to prevent different diseases and for medical and clinical applications. Consuming prebiotics gives impeccable benefits since it aids in gut microbial balance. Prebiotic research is primarily concerned with the influence of intestinal disorders. The proposed review will describe recent data on the sources, structures, implementation of prebiotics and potential mechanisms in preventing and treating various disorders, with an emphasis on the gut microbiome. Prebiotics have a distinctive impact on the gastro intestine by explicitly encouraging the growth of probiotic organisms like Bifidobacteria and Lactobacilli. This in turn augments the body's inherent ability to fend off harmful pathogens. Prebiotic carbohydrates may also provide other non-specific advantages due to their fermentation in the large intestine. Additional in vivo research is needed to fully comprehend the interactions between prebiotics and probiotics ingested by hosts to improve their nutritional and therapeutic benefits., 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 Elsevier Ltd. All rights reserved.)

Background: The production of inflammatory factors in periodontium is increased by LPS, particularly from P. gingivalis, and the damage to periodontal tissues is exacerbated. Exosomes from periodontal ligament stem cells change regeneration and repair brought on by bacterial LPS. MiRNAs are carried by exosomes to recipient cells to affect epigenetic functions. Thus, this study aims to utilize deep learning algorithms to uncover novel micro-RNA biomarkers in bacterial LPS-exposed PDLSC stem cells to understand the activation pathway., Methods: Using NCBI GEO DATA SET GSE163489, the most differentially expressed micro RNAs were found to differ between healthy and LPS-induced PDLSC cells. Deep learning analysis, employing a Random Forest, Artificial Neural Network c, a Support Vector Machine (SVM), and a Linear Regression model implemented within the orange data mining toolkit, identified novel microRNA biomarkers. The orange data mining toolkit was utilized for deep learning analysis of microRNA expression data, providing a user-friendly environment for machine learning tasks like classification, regression, and clustering., Results: Random Forest emerged as the superior model, achieving the highest R 2 score (.985) and the lowest RMSE (0.189) compared to Neural Networks ( R 2  = .952, RMSE = 0.332), Linear Regression ( R 2  = .949, RMSE = 0.343), and SVM ( R 2  = .931, RMSE = 0.398). This suggests its superior ability to capture the underlying patterns in the microRNA expression data. Given its robust performance, Random Forest holds promise for identifying novel biomarkers, developing more accurate diagnostic tools, and potentially guiding the stratification of patients for targeted therapeutic interventions in periodontal disease., Conclusion: The current study utilizes deep learning analysis of microRNA expression data to identify novel biomarkers associated with inflammasome activation and anti-apoptotic pathways. These findings hold promise for guiding the development of novel therapeutic strategies for periodontal disease. However, future studies are warranted to validate these biomarkers using independent datasets and experimental methods., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The review focuses primarily on collating and analyzing the mechanistic research data that discusses the function of prebiotics to halt the frailty of musculoskeletal system. Musculoskeletal diseases (MSDs) are frequently reported to co-occur within their own categories of conditions, such as osteoarthritis, rheumatoid arthritis, gouty arthritis, and psoriatic arthritis owing to their overlapping pathogenesis. Consequently, the same drugs are often used to manage the complications of most types. A few recent studies have addressed the therapeutic functions of gut microbes toward those commonly shared MSD pathway targets. Improving microbial diversity and enriching their population in the gut would promote the regeneration and recovery of the musculoskeletal system. Prebiotics are usually nondigestible substrates that are selectively used or digested by the gut microbes conferring health promotion. The microbial fermentation of prebiotics generates numerous host-beneficial therapeutic molecules. This study inspects the presumptive functions of plant-derived prebiotics for the growth and restoration of intestinal microbiota and the consequent improvement of skeletal health. The review also highlights the discrete functions of prebiotics against inflammation, autoimmunity, infection, physiologic overloading mechanism, and aging-associated loss of metabolism in MSD., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint damage. Existing treatment options primarily focus on managing symptoms and slowing disease progression, often with side effects and limitations. The gut microbiome, a vast community of microorganisms present in the gastrointestinal tract, plays a crucial role in health and disease. Recent research suggests a bidirectional relationship between the gut microbiome and RA, highlighting its potential as a therapeutic option. This review focuses on the interaction between the gut microbiome and RA development, by discussing how dysbiosis, an imbalance in gut bacteria, can contribute to RA through multiple mechanisms such as molecular mimicry, leaky gut, and metabolic dysregulation. Probiotics, live microorganisms with health benefits, are emerging as promising tools for managing RA. They can prevent the negative effects of dysbiosis by displacing harmful bacteria, producing anti-inflammatory metabolites like short-chain fatty acids (SCFA), Directly influencing immune cells, and modifying host metabolism. animal and clinical studies demonstrate the potential of probiotics in improving RA symptoms and disease outcomes. However, further research is needed to optimize probiotic strains, dosages, and treatment protocols for personalized and effective management of RA. This review summarizes the current understanding of the gut microbiome and its role in RA and discusses future research directions. In addition to the established role of gut dysbiosis in RA, emerging strategies like fecal microbiota transplantation, prebiotics, and postbiotics offer exciting possibilities. However, individual variations in gut composition necessitate personalized treatment plans. Long-term effects and clear regulations need to be established. Future research focusing on metagenomic analysis, combination therapies, and mechanistic understanding will unlock the full potential of gut microbiome modulation for effective RA management., Competing Interests: Declaration of competing interest We are thankful to the funding agency, Department of Science and Technology, Science and Engineering Research Board (SERB), Government of India (SPG/2021/003709) for supporting this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cancer formation is defined as the unrestrained proliferation of cells due to various factors acting as a causing agent. A limited number of over-expressed transcription factors are contributed to the development of numerous types of cancer. The metastatic regulator protein BTB And CNC Homology 1 (BACH1) is Cap 'N' Collar (CNC) and it belongs to a basic region leucine zipper (bZIP) family. The presence of the least level concentration of intracellular heme BACH1 forms heterodimers with musculo aponeurotic fibrosarcoma (sMAF) proteins and inhibits or induces the target gene expression. Based on the previous studies, BACH1 plays a critical player in the conditions of senescence and oxidative stress, cycling of cell life, heme degradation pathway and cancer, especially in metastasis. Discovering new anti-cancer drugs (identification of bioactive compounds) stages finally needs to inhibit the target protein. This present study is aimed to screen and identify stability, binding affinity and analysis of pharmacokinetics of selected compounds through structural screening, ADMET, DFT and MESP. From this study, it is revealed that Rapanone and Nectandrin B have the potential to alter the degree of gene expression via binding with the BACH1 allosteric region which will further change the degree of expression of BACH1 downstream target genes involved in the regulation of cancer progression particularly in metastasis. The two plant origin compounds Rapanone and Nectandrin B might be novel candidates for developing anti-cancer drugs. The predicted compounds were further validated through in-vitro experimental approaches.Communicated by Ramaswamy H. Sarma.

In the design and development of therapeutic agents, macromolecules with restricted structures have stronger competitive edges than linear biological entities since cyclization can overcome the limitations of linear structures. The common issues of linear peptides include susceptibility to degradation of the peptidase enzyme, off-target effects, and necessity of routine dosing, leading to instability and ineffectiveness. The unique conformational constraint of cyclic peptides provides a larger surface area to interact with the target at the same time, improving the membrane permeability and in vivo stability compared to their linear counterparts. Currently, cyclic peptides have been reported to possess various activities, such as antifungal, antiviral and antimicrobial activities. To date, there is emerging interest in cyclic peptide therapeutics, and increasing numbers of clinically approved cyclic peptide drugs are available on the market. In this review, the medical significance of cyclic peptides in the defence against viral infections will be highlighted. Except for chikungunya virus, which lacks specific antiviral treatment, all the viral diseases targeted in this review are those with effective treatments yet with certain limitations to date. Thus, strategies and approaches to optimise the antiviral effect of cyclic peptides will be discussed along with their respective outcomes. Apart from isolated naturally occurring cyclic peptides, chemically synthesized or modified cyclic peptides with antiviral activities targeting coronavirus, herpes simplex viruses, human immunodeficiency virus, Ebola virus, influenza virus, dengue virus, five main hepatitis viruses, termed as type A, B, C, D and E and chikungunya virus will be reviewed herein., Competing Interests: Conflict of interestThe authors have no relevant financial or nonfinancial interests to disclose., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: History of rheumatoid arthritis (RA) increases risk of periodontal diseases. A pro-inflammatory condition noted in periodontitis is considered a trigger for RA. Thus, periodontal treatment aimed at attenuating the pro-inflammatory state could aid in potentially reducing the risk of RA., Aims: The objective of this research was to assess the effect of periodontal therapy on rheumatoid factor, Disease Activity Score-28, anti-citrullinated protein antibody, and C-reactive protein levels in patients with chronic periodontitis (CP) and RA., Materials and Methods: The sample consisted of 28 patients with CP and RA. The study was designed to be a double-blind, randomised controlled clinical study. The samples were randomly categorised to either the treatment group (n = 13) or the control group (n = 15). CP status (plaque index, bleeding on probing, probing pocket depth, clinical attachment loss), clinical rheumatologic status (Disease Activity Score), and biochemical status (C-reactive protein, anti-citrullinated protein antibody, and rheumatoid factor) were assessed at baseline and at follow-up at 8 to 12 weeks., Results: The treatment group showed a highly statistically significant reduction in bleeding on probing (P < .005), probing pocket depth (P < .001), plaque index (P < .001), and C-reactive protein (P < .001); a gain in the clinical attachment loss (P < .001) and an improvement in Disease Activity Score-28 (P = .001) were observed at reassessment following nonsurgical periodontal treatment as compared to the control group. However, blood serum anti-citrullinated protein antibody (P = .002) and rheumatoid factor levels (P = .351) were found to increase from baseline to 8 to 12 weeks following subgingival scaling and root planing., Conclusions: Reduction of inflammation in the periodontium by nonsurgical periodontal therapy did not reduce anti-citrullinated protein antibody and rheumatoid factor levels. However, it has shown improvement in periodontal conditions, and remarkable changes were observed in the clinical Disease Activity Score and C-reactive protein levels of individuals with RA., Competing Interests: Declaration of Competing Interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Brassica juncea (BJ) is a familiar edible crop, which has been used as a dietary ingredient and to prepare anti-inflammatory/anti-arthritic formulations in Ayurveda. But, the scientific validation or confirmation of its therapeutic properties is very limited. This study was performed to determine the efficiency of BJ leaves for the treatment of Rheumatoid arthritis using in vivo and in silico systems. Standard in vitro procedures was followed to study the total phenolic, flavonoid contents and free radical scavenging ability of the extracts of BJ. The effective extract was screened and the presence of bioactive chemicals was studied using HPLC. Further, the possible therapeutic actions of the BJ active principles against the disease targets were studied using PPI networking and docking analysis. IL2RA, IL18 and VEGFA are found to be the potential RA target and the compounds detected from BJ extract have shown great binding efficiency towards the target from molecular docking study. The resulting complexes were then subject to 100 ns molecular dynamics simulation studies with the GROMACS package to analyze the stability of docked protein-ligand complexes and to assess the fluctuation and conformational changes during protein-ligand interactions. To confirm the anti-arthritic activity of BJ, the extract was tested in CFA-induced arthritic Wistar rats. The test groups administered with BJ extract showed retrieval of altered hematological parameters and substantial recovery from inflammation and degeneration of rat hind paw.Communicated by Ramaswamy H. Sarma.

Ethnopharmacological Relevance: Cardiospermum halicacabum Linn. (C. halicacabum) is one of the well-known leafy green vegetables in India. It is an herbaceous climber from the Sapindaceae family which is found in almost every Continent and Oceania. In the traditional Indian medicine systems, this plant is used for the treatment of rheumatism, abdominal pain, orchitis, dropsy, lumbago, skin diseases, cough, nervous disorders, and hyperthermia., Aim of the Review: This review presents the current information about ethnomedical uses and progress on geographical distribution, pharmacological activities, phytochemistry, micropropagation, and toxicity of C. halicacabum. Also, critically summarizes the relationship between the reported pharmacological activities and the traditional usages along with the future perspectives for research on this medicinal plant., Materials and Methods: The data on C. halicacabum were collected using multiple internet sources such as Google Scholar, Science Direct, Taylor & Francis, PubMed, Web of Science, Springer Link, Wiley online, and plant databases., Results: Chemical characterization using LC-MS/MS, HPLC, and NMR exposed the presence of chlorogenic acid, caffeic acid, coumaric acid, luteolin-7-o-glucuronide, apigenin-7-o-glucuronide, and chrysoeriol in different parts of C. halicacabum. Based on the outcomes of this review, the main bioactive compounds found in C. halicacabum include phenols, phenolic acids, flavonoids, flavonoid glycosides, and flavonoid glucuronides. Besides the above-mentioned constituents, palmitic acid, oleic acid, stearic acid, linolenic acid, eicosenoic acid, and arachidic acid are the compounds that constitute the fatty acid profile of C. halicacabum seeds. Specifically, Cardiospermin, a bioactive compound isolated from the root extract of C. halicacabum has been recognized for its anxiolytic activity. Moreover, C. halicacabum showed a broad spectrum of pharmacological activities including anti-inflammatory, anti-arthritic, anti-diabetic, anxiolytic activity, antiulcer, apoptotic activity, antibacterial, antiviral, anti-diarrheal, antioxidant, hepatoprotective, and nephroprotective properties. However, the bioactive compounds responsible for most of the above therapeutic properties have not been elucidated till now., Conclusion: Phytochemicals from C. halicacabum showed noticeable pharmacological effects against plethora of health disorders. Some of the traditional applications were supported by modern scientific studies, however, more pharmacological evaluations should be conducted to validate other traditional uses of C. halicacabum. Despite C. halicacabum's vast pharmacological activity, additional human clinical trials are needed to determine the potent and safe dosages for the treatment of various health abnormalities. Besides, bioassay-guided isolation of active constituents, pharmacokinetic evaluations and identification of their mode of action are recommended for future investigations on C. halicacabum to unveil its therapeutic drug leads. Overall, this review suggests that C. halicacabum could be a new source of functional foods., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Human food is composed of loads of chemicals derived naturally as well as unintentionally through environmental sources. Food additives added purposefully, play an important role in the palatability of foods. Most additives are synthetic whose essentiality in food processing is well-known however their health risks are not overlooked. The palatability of food should not only stimulate our eating desire alone but, also assure sufficient quality and safety. Application of food additives varies from region to region due to cultural or ethnic differences and the local food availability. There are about more than ten thousand chemicals allowed in food whereas due to weak enforcement, it becomes onerous for regulatory bodies identifying chemicals that are inadequately or not tested at all for safety. The hiking population and urbanization in many industrialized and developing countries resulted in life-style changes including culinary and eating choices. Particularly, the modern way of this globalised life demands ready-to-cook or ready-made foods, snacks, sweets, soft drinks, desserts, confectionery and so on. These sorts of food would be most uninteresting unless processed with additives. This puts food industries under demand to robustly supply foods that are either partially, fully or ultra-processed using plenty of additives. Recent research warns consuming food additives may result in serious health risks, not only for children but also for adults. Growing body of studies on food additives in various experimental animals, cell cultures, and human population suggest elevation of number of obesity and diabetes risk factors i.e. adiposity, dyslipidemia, weight gain, hyperglycaemia, insulin resistance, glucose intolerance, energy imbalance, hormonal intervention etc. Hence, it is important to identify and explore food obesogens or obesogenic food additives posing potential impact. Based on the recent toxicological findings, the review aspires to establish the association between exposure of food obesogen and metabolic disruption which may help filling knowledge gaps and distributing more knowledge, awareness and effective measures to implement treatment and preventive strategies for metabolic syndrome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as 'insomnia disorder' to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study aimed to prepare the fortified rice/flour with Cissus quadrangularis (CQ) stem powder to eliminate nutritional deficiency and improve bone health. Mineral analysis by atomic absorption spectroscopy revealed that the CQ stem has adequate quantities of calcium, magnesium, and a moderate amount of phosphorous to meet the Recommended Dietary Allowance (RDA). Thus, the rice and flour were fortified with freeze-dried CQ stem powder to improve its nutraceutical contents. The fortification was done using standard vacuum impregnation and blending process. Furthermore, the recuperative activity of prepared fortified rice (CQFR) and flour (CQFF) was tested in chemically induced osteoporosis and osteoarthritis animal models. The efficiency of CQ fortified diet against these complications was confirmed by hematology, radiology, and histopathological analysis. The rat groups fed with CQFF/CQFR diet showed significant improvement from calcium deficiency and its allied physiological damage. Thus, this study confirms that the CQ fortified rice would provide recovery from skeletal complications associated with calcium deficiency through fixing both homeostasis and bio-accessibility of the calcium. PRACTICAL APPLICATIONS: Micronutrient and mineral deficiency is relatively higher in the regions where rice/rice products are consumed as a staple diet. Dietary intake of calcium and some essential minerals have major influences on bone and joint health. Cissus quadrangularis (CQ) is a familiar herb, conventionally used in India to fix broken bones and strengthen the skeletal system. The Atomic absorption spectroscopy data from this study showed that the CQ stem holds a high amount of calcium and other essential minerals to promote skeletal health. Preparation of fortified rice and flour with CQ stem would be a beneficial source of the essential minerals/ bioactive principles to promote and sustain skeletal health in the underprivileged population. These study data substantiated the practical application of producing the CQ fortified nutraceutical staple diet, especially to the people who are afflicted with morbid skeletal complications., (© 2021 Wiley Periodicals LLC.)

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Rheumatoid Arthritis (RA) is an autoimmune disease that commences as inflammation and progressively destroys the articular joint. In this study, we assess the anti-rheumatic potential of the monoterpenoid class of thymol conjugated with Carbon Dots (CDs). Waste biomass in the form of dried rose petals was chosen as a precursor for the synthesis of CDs via a one-step hydrothermal bottom-up methodology. The prepared CDs exhibited absorption in the near-visible region, and unique excitation-dependent emission behaviour was confirmed from UV-Visible and fluorescence measurements. The surface morphology of CDs was confirmed by SEM and HR-TEM analysis to be quasi-spherical particles with an average size of ∼5-6 nm. The presence of various functional moieties (hydroxyl, carbonyl, and amino) was confirmed via FT-IR measurement. The graphitization of CDs was confirmed by the D and G bands for sp2 and sp3 hybridization, respectively, through Raman analysis. Esterification methodology was adopted to prepare the CDs-thymol conjugate and confirmed via FT-IR analysis. CDs play the role of a nanocarrier for thymol, an anti-arthritic agent. The bioactive compound of thymol showed potent anti-arthritic activity against RA targets through in silico docking studies. Further, the in vivo studies revealed that CDs-thymol conjugates (10 mg per kg body weight) showed a significant reduction in rat paw volume along with reduced levels of RF and CRP (2.23 ± 0.42 IU ml-1 and 16.96 ± 0.22 mg ml-1) when compared to the disease control rats. X-ray radiography and ultrasonic imaging revealed less bone destruction, joint derangement, and swelling in arthritis-induced Wistar rats. They could also potentially improve the Hb (14.14 ± 0.19), RBC (6.01 ± 0.11), PCV (6.01 ± 0.11) levels and elevate the status of antioxidant enzymes (GPx, SOD, MDA), and the activity was comparable to the standard drug, ibuprofen (10 mg kg-1), suggesting that the CDs-thymol conjugate at 10 mg kg-1 could act as a strong anti-arthritic agent. This work is evidence for the utilization of waste biomass as a value-added product such as a nanocarrier for biomedical applications.

Male reproductive dysfunction is one of the common complications of diabetes mellitus that causes infertility. This study was designed to investigate the protective effect of Momordica cymbalaria ( M. cymbalaria ) extracts on diabetes mediated reproductive toxicity in male Wistar rats. The induction of diabetes was performed using a single intraperitoneal injection of alloxan (120 mg/kg). Skin and seed extracts (250 and 500 mg/kg) of M. cymbalaria were orally administered to alloxan-induced diabetic male rats for 28 days. Postprandial blood glucose (PBG) levels were recorded at 7-day interval for four weeks. The effects of the treatment on blood glucose, weight of reproductive organs, sperm count, testosterone levels, antioxidant capacity, and histomorphology were evaluated. Treatment with the above extracts of M. cymbalaria significantly ( p  < 0.05) improved the reproductive parameters as well as the antioxidant levels superoxide dismutase (SOD) and glutathione-s-transferase (GST) in the diabetic rats. Also, oral treatment with M. cymbalaria extracts significantly reduced the PBG and malondialdehyde (MDA) levels. Further, it revived the histomorphology of reproductive organs in diabetic rats. Interestingly, skin extract at a dose of 500 mg/kg was found to be more efficient in elevating the level of testosterone and sperm count in the diabetic rats. Based on the results, it is clear that M. cymbalaria not only regulates the postprandial blood glucose levels but also improves the reproductive health in the diabetic state., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© King Abdulaziz City for Science and Technology 2021.)

Chronic hyperglycemia and oxidative stress promote non-enzymatic glycation that leads to the production of advanced glycation end products (AGEs). AGEs casue significant damage to physiological proteins which result in several complications. The scenario also corresponds to the chronic consumption of a diet rich in AGEs. Despite understanding these mechanisms at the molecular level, the discovery of new drugs for these complications is under progress. Natural compounds might have great therapeutic potential for treating glycative consequences. In view of this, the study aimed to evaluate fruit extracts of Hylocereus polyrhizus towards determining its phenolics and flavonoid contents, as well as assessing it's in vitro antiglycative potential through the use of multistage glycation markers (early, intermediate and end stage products of β-aggregation) in sugar-protein model. In vitro hypoglycemic activity of H. polyrhizus extracts was evaluated through α-amylase and α glucosidase inhibitory activities. In vitro antioxidant potential of the fruit extracts was also examined against different free radical types including DPPH and ABTS. Among the different in vitro assays performed, methanolic and acetone extracts of the fruit, with higher phenolics and flavonoid content, have exerted significant antiglycation and antioxidant activities than other extracts namely aqueous, ethanol, hydro-ethanol, hydro-methanol, and petroleum ether. Ultra-Performance Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry (UPLC-ESI-MS/MS) analysis was employed to identify active polyphenolics that may be responsible for the antiglycative potential of H. polyrhizus. The analysis revealed some high-profile compounds that have well documented for their therapeutic benefits. Additionally, In silico analysis also showed the possible connection between identified compounds and mechanisms of action. 4- Prenylresveratrol, Vicenin, and Luteolin had observed as effectively interact with target protein in molecular docking analysis. This suggests H. polyrhizus as a good source of anti-glycation and antioxidants that may have potential applications for the treatment and prevention of glycation associated diabetic and aging complications., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This investigation is to find a prolonged or delayed drug release system, exclusively for the treatment of hepatitis-B to reduce the side effects, which arise when conventional solid dose forms are administered. To pursue this goal, lamivudine-loaded Eudragit-coated pectin microspheres have been formulated employing water/oil (W/O) emulsion evaporation strategy. The formulation was optimised using a 3 4 factorial design. A drug to polymer ratio of 1:2, the surfactant of 1 ml, the volume of 50 ml of processing medium with a stirring speed of 2500 rpm were found to be the optimal parameters to obtain the lamivudine-loaded Eudragit-coated pectin microspheres formulation with a high drug entrapment efficiency of 89.44% ± 1.44%. The in vitro release kinetics of lamivudine was a suitable fit to the Higuchi model, indicating a diffusion-controlled release with anomalous transport. The obtained microspheres were then subjected to different characterisation studies, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The results of this study clearly indicate that Eudragit-coated pectin microspheres could be the promising controlled release carriers for colon-specific delivery of lamivudine in the presence of rat cecal content., (© 2021 The Authors. IET Nanobiotechnology published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Rheumatoid Arthritis is a chronic, inflammatory, and systemic autoimmune disease, it affects elders worldwide. Herbal medicines have been used for the treatment of various ailments from ancient times. Betelvine (Piper betle L.) leaves have long been used in Asian countries as a medicine to relieve pain and some metabolic diseases. The present study of methanolic extract of phytochemical analysis confirms the presence of alkaloids, tannins, terpenoids, saponins, steroids, total flavonoids and total phenols. GC-MS analysis of MeOH extract of Piper betle (PBME) revealed the presence of 40 bioactive compounds. In vitro antioxidant and anti-inflammatory assays showed greater inhibitory effect. The anti-arthritic effects of PBME at 250 and 500 mg/kg concentration showed recovery from joint damage in in vivo rat model. Among the 40 GC-MS derived bioactives, 4-Allyl-1,2-Diacetoxybenzene exhibited the higher interactions with minimized binding energy to the RA targets of MMP 1 (-6.4 kcal/mol), TGF-β (-6.9 kcal/mol), IL-1β (-5.9 kcal/mol). Further, the effect of PBME extract against RA molecular disease targets (IL-1β, MMP1 and TGF- β) were studied using Real-time PCR. These results substantiate that P. betle leaves could be a source of therapeutics for the treatment of rheumatoid arthritis., 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 © 2020 Elsevier Inc. All rights reserved.)

The Cissus quadrangularis (CQ) stem has interesting nutritional and pharmacological properties to promote the health of the skeletal system. It is a well-recognized plant in the conventional system of medicine in India for treating bone and joint-associated complications. This study focuses on identifying the active constituents from the stem and root extracts of CQ and validating its anti-osteoarthritic activity by the in vivo model. Notable levels of phenolics and flavonoids were found in the ethanol extracts of both CQ stem (CQSE) and root (CQRE), among other solvent fractions. UPLC-MS/MS analysis of these selective extracts resulted in different classes of active compounds from both positive and negative ionization modes. By analyzing their mass spectra and fragmentation pattern, 25 active compounds were identified. The CQSE and CQRE extracts, along with the standard drug (naproxen), were further tested in mono-sodium iodoacetate-induced experimental OA animals. The modulatory effects of the test extracts were assessed by haematology, synovial and cartilage marker profiling, radiology and histopathological analysis. The in vivo findings from the biochemical and physiological studies have led to the conclusion that the CQSE extract is a good choice for the management of OA. The results were substantially better than CQ root extract and naproxen drug-treated groups. Thus, CQS has bioactive constituents, which could facilitate recovery from joint tissue damage, cellular metabolism and associated risk factors attributable to dysfunctions in OA incidence and progression.

Ethnopharmacological Relevance: Momordica cymbalaria, a wild vegetable belongs to the Cucurbitaceae family, has long been used as a food and a remedy for diabetes mellitus in the Asian native medicinal system., Aim of the Study: This study aims to evaluate the efficacy of ethanolic extract of skin (EESK) and methanolic extract of seed (MESE) of M. cymbalaria (MC), for their hypoglycemic and hypolipidemic effects in alloxan induced diabetic rats., Materials and Methods: The diabetes induced rats were given skin and seed extracts at doses 250 and 500 mg/kg b.w. p.o. for 28 days. Alloxan monohydrate (120 mg/kg) was used to induce diabetes mellitus. Daily food and water intake were assessed. Blood glucose levels and body weights were measured every 7 days throughout the experiment. Antioxidant assays, different biochemical and glycemic parameters were evaluated. Histopathological studies on pancreas, liver and kidney were also studied., Results: Treatment of EESK and MESE showed dose significant decrease in fasting blood glucose level (FBG) in experimental diabetic animals with significant reduction in food and water intake and increase in body weight. Findings confirmed the hypoglycemic and hypolipidemic effects of EESK and MESE in the experimental groups. The impaired glucose tolerance and altered activities of the hepatic enzymes such as AST, ALT and ALP levels of diabetic rats were significantly improved by the administration of EESK and MESE. Oral treatment with MC extract for 28 days demonstrated significant protective effects on the lipid profile, biochemical parameters and antioxidant levels. Besides, biochemical findings were supported by histopathological investigations., Conclusion: These results suggest that the treatment with EESK and MESE of MC at a dose of 500 mg/kg b.w. have better protective effects against hyperglycemia, hyperlipidemia and oxidative stress generated during diabetes justifying the use of the plant in traditional systems of medicine., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mankind exposure to chemicals in the past century has increased dramatically throughout environment. There is no question that chemicals interfere with the physiology of biological system. Abundance of chemicals is documented to be detrimental to human and wildlife. The mammalian endocrine system is comprised of many interacting tissues mediate themselves through hormones that are essential for metabolism, growth and development. Humans secrete over fifty different hormones to orchestrate major physiological functions however; these vital functions can be intervened by huge number of internal and external chemical stressors that are identified as endocrine disruptors. Advanced glycation end products (AGEs), familiarly known as Maillard products, formed through non-enzymatic glycation whose production is augmented on aging as well as environmental stressors. Processed foods have become very popular today due to their taste, convenience, and inexpensiveness. Manufacture of these day-to-day foods involves extreme temperatures on processing results in the formation of AGEs could independently promote oxidative stress, aging, diabetes, cancer, degenerative diseases, more fascinatingly hormonal disruption is the subject of interest of this review. Based on some substantial observations documented till time, we discuss the emergence of dietary AGEs as potential endocrine disruptors by emphasizing their occurrence, mechanisms and participation in endocrine interruption. Both economically and in terms of human life, AGEs may represent an enormous cost for the future society. Therefore, by explicating their novel role in endocrine diseases, the review strives to make an impact on AGEs and their exposure among public as well as scientific communities., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Type 2 Diabetes Mellitus (T2DM) is very common metabolic disorder affecting people of all age groups. The change in life style and environmental factors are the considerable factors which are involved in the development of the disorder. The different parts of medicinal plants vary in their composition of bioactive compounds. There are reports on antidiabetic activity of C. auriculata L. flower and leaves. Traditionally bud of C. auriculata L. is used to treat diabetes rather than flower. This study aims to explore the antidiabetic efficiency of bud and flower and to identify the differential composition of phycompounds present in bud and flower parts of C. auriculata L. The compounds present in the bud and flower parts were identified using LC-ESI/MS analysis. Antidiabetic activity of C. auriculata L. bud and flower parts was studied in high fat diet (HFD) and streptozotocin (STZ) induced diabetic rats. During which parameters such as feed intake, water intake, and body weight were monitored. After 21 days of the study, blood parameters like insulin, glucose, lipid profile, hepatic function test, renal function test and oxidative stress markers were analysed. Real time PCR was done to monitor the expression of IRS2 and GRIA2 genes. The LC-ESI/MS analysis showed the presence of various phenolics and flavonoid compounds specific to bud and flower parts. The antidiabetic activity results showed that the animal treated with C. auriculata L. bud ethanol extract (CABE500) could better reverse and control the progression of the disease compared to the flower ethanol extract. The gene expression studies revealed that regulation of IRS2 gene occurred in bud but not in flower extract treated animal livers and no differential expression of GRIA2 gene in all the experimental groups. C. auriculata L. bud extract can potentially better control the diabetes compared to the flower extract., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: The hyperoxidative and a modified inflammatory state in obese individuals cause higher susceptibility to bacterial infection which influences the initiation and progression of periodontal disease., Aim: Our study was aimed to evaluate the role of nonsurgical periodontal therapy on the clinical parameters such as gingival index (GI), plaque index, pocket probing depth (PPD) and clinical attachment level (CAL), plasma-reactive oxygen metabolite (ROM) levels, and gingival crevicular fluid (GCF) resistin and serum resistin levels in obese or overweight and normal weight individuals with periodontitis., Material and Methods: Sixty individuals of age between 35 and 45 years of both the sexes were selected and categorized into two groups as thirty overweight or obese individuals with chronic periodontitis (Group I) and thirty normal weight individuals with chronic periodontitis (Group II). Clinical parameters, plasma ROM levels, and serum and GCF resistin levels were assessed at baseline and 2 months after periodontal therapy in both the groups and compared., Results: Intergroup comparison of clinical parameters (GI, CAL, PPD) 2 months after therapy showed a significant difference with more reduction in Group II compared to Group I. On comparison, mean plasma ROM, GCF, and serum resistin levels at baseline was higher in Group I compared to Group II. When plasma ROM, GCF, and serum resistin levels were compared 2 months after therapy, the reduction was more in Group II compared to Group I., Conclusion: It is concluded that along with periodontal therapy, motivation of patients for weight reduction program is mandatory for obese or overweight individuals with periodontitis in order to improve periodontal health., Competing Interests: There are no conflicts of interest.

Purpose: Pedalium murex is a fruit-bearing annual herb, native to South India, Mexico and tropical Africa. The plant is widely used to treat numerous diseases including gastric ulcer, asthma, heart problems, anti inflammatory activity and particularly urinary disorders. Traditional medicine has become a skilled approach by means of rational values in handling a variety of diseases and developing an affordable phytotherapy. It is proclaimed that P.murex is an expensive source of unique bioactive compounds for the development of natural medicines against various diseases., Conclusion: This review provides the details of ethno pharmacological importance of P. murex, as well as its composition of phytochemicals, biological activities and traditional usage. Also provides a source for future studies such as isolation of bioactive components and mechanism of action of this plant extract., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Tumor necrosis factor-alpha (TNF-α) is indicated to play a major function in chronic inflammatory disorders., Objective: To assess and compare the cytokine level (TNF-α) in the serum of chronic periodontitis (CP), rheumatoid arthritis (RA), RA with CP, and healthy volunteers., Materials and Methods: This original research was carried out on 80 participants, divided into Group-I 20 RA patients, Group-II 20 CP patients, Group III 20 RA with CP (RA + CP), and Group IV 20 healthy volunteers. Clinical periodontal and rheumatological parameters were assessed in all the four groups. Blood serum samples have been collected from all individuals and investigated for levels of TNF-α by mean of enzyme-linked immunosorbent assay., Results: TNF-α level were remarkably elevated in the RA+CP group (30.5±2.2) followed by RA group (17.9 ± 3.6), and CP group (11.9 ± 0.96) when compared with the controls (5.5 ± 3.3). The results showed a statistical significance of P < 0.001. Correlation was not observed on comparision of clinical periodontal parameters and Rheumatological parameters with TNF-α levels., Conclusion: The outcome of this present research revealed the presence of higher levels of TNF-α in individuals with RA with CP in our samples., Competing Interests: There are no conflicts of interest.

Background: Protease-activated receptors (PAR-1 and PAR-2) are found to be immensely exhibited in the periodontal tissues. These receptors are involved in the inflammatory and repair processes. Activation of PARs is mainly by the bacterial and endogenous enzymes. The aim of the study was to determine the role of PAR-1 and PAR-2 in initiating periodontal inflammation and to immunolocalize these receptors in the gingival tissues of healthy and chronic periodontitis individuals., Materials and Methods: A total of 50 patients were selected for this study, of which 25 were healthy controls and 25 were chronic periodontitis patients. Gingival tissues were excised from the marginal gingiva and interdental papilla under local anesthesia (xylocaine with 2% adrenaline) during crown lengthening procedure or during periodontal therapy depending on the respective groups. Immunohistochemical analyses of PARs were done by staining the samples with hematoxylin and eosin and with primary and secondary antibody for PAR-1 and PAR-2., Results: The Hematoxylin and Eosin staining showed more inflammatory changes in the periodontitis group compared to healthy gingiva. In chronic periodontitis, PAR-1-positive cells were seen in the basal layer with a weak expression and were showing negative expression in the superficial layer. In consideration of PAR-2, there was a very strong expression up to the superficial layer of the epithelium, compared to PAR-1. On comparing the intensity of staining in the connective tissue of chronic periodontitis sample, there was an increased expression of PAR-2 compared with PAR-1. A low positive expression of PAR-1 and PAR-2 was observed in the epithelium and connective tissue of the healthy tissues., Conclusion: The results clearly demonstrated the role of PAR-1 and 2 in periodontal inflammation., Competing Interests: There are no conflicts of interest.

Cyanobacterial KnowledgeBase (CKB) is a free access database that contains the genomic and proteomic information of 74 fully sequenced cyanobacterial genomes belonging to seven orders. The database also contains tools for sequence analysis. The Species report and the gene report provide details about each species and gene (including sequence features and gene ontology annotations) respectively. The database also includes cyanoBLAST, an advanced tool that facilitates comparative analysis, among cyanobacterial genomes and genomes of E. coli (prokaryote) and Arabidopsis (eukaryote). The database is developed and maintained by the Sub-Distributed Informatics Centre (sponsored by the Department of Biotechnology, Govt. of India) of the National Facility for Marine Cyanobacteria, a facility dedicated to marine cyanobacterial research. CKB is freely available at http://nfmc.res.in/ckb/index.html.

Passivity based control of DC motor in sensorless configuration is proposed in this paper. Exact tracking error dynamics passive output feedback control is used for stabilizing the speed of Buck converter fed DC motor under various load torques such as constant type, fan type, propeller type, and unknown load torques. Under load conditions, sensorless online algebraic approach is proposed, and it is compared with sensorless reduced order observer approach. The former produces better response in estimating the load torque. Sensitivity analysis is also performed to select the appropriate control variables. Simulation and experimental results fully confirm the superiority of the proposed approach suggested in this paper.

Skin grafts are indicated when there is a major loss of skin. Full-thickness skin graft is an ideal choice to reconstruct defect of irregular surface that is difficult to immobilize. Full-thickness mesh grafts can be applied to patch large skin defect when there is less donor site in extensively traumatized and burned surgical patients. The concept of using natural biomaterials such as keratin, basic fibroblast growth factor is slowly gaining popularity in the field of medical research to achieve early healing. The main objective of this study is to evaluate the efficacy of gelatin conjoined with keratin processed from the poultry feather and commercially available basic fibroblast growth factor (bFGF) as a sandwich layer in promoting the viability of full-thickness skin mesh grafts. The efficacy was assessed from the observation of clinical, bacteriological, and histopathological findings in three groups of experimental dogs. The clinical observations such as color, appearance and discharge, and hair growth were selected as criteria which indicated good and early acceptance of graft in keratin-gelatin (group II). On bacteriological examination, Staphylococcus aureus and Proteus was identified in few animals. Histopathological study of the patched graft revealed early presences of hair follicles; sebaceous gland, and normal thickness of the epidermis in keratin-gelatin in group II treated animals compared with other group (group I-control, group III-bFGF-gelatin)., ((c) 2007 Wiley Periodicals, Inc.)