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When glucose and Amadori products are auto-oxidized, glycation occurs, resulting in the formation of early (Amadori) and late advanced glycation end products (AGEs), as well as free radicals. Glycation and an increase in free radical activity induce diabetic complications. Antioxidant and antiglycation compounds may aid in the prevention of oxidation and glycation. The goal of this study was to assess the antiglycation and antioxidant capacity of C-phycocyanin (C-PC) derived from Plectonema sp. The DPPH (1, 1-diphenyl-2-picrylhydrazyl), nitric oxide, hydroxyl radical scavenging activities and ferric ions reducing antioxidant power (FRAP) assays were used to assess antioxidant activity, while an in vitro bovine serum albumin-methyl glyoxal glycation (BSA-MG) model was used to assess glycation inhibitory potential. Glycation inhibition was measured using a variety of spectroscopic and biochemical parameters, including UV-visible & fluorescence spectroscopy, ketoamine, carbonyl and hydroxymethyl furfural content, as well as free lysine & free arginine estimations. In vitro, C-PC exhibited dose-dependent potent antioxidant activity, but lacked significant antiglycation potential. As a result, it is recommended that further studies be conducted to evaluate the antiglycation potential of C-PC.

Nanotechnology is considered a successful approach for cancer diagnosis and treatment. Preferentially, cancer cell recognition and drug targeting via nano‐delivery system include the penetration of anticancer agents into the cell membrane to damage the cancer cell by protein modification, DNA oxidation, or mitochondrial dysfunction. The past research on nano‐delivery systems and their target has proven the beneficial achievement in a malignant tumor. Modern perceptions using inventive nanomaterials for cancer management have been offered by a multifunctional platform based on various nano‐carriers with the probability of imaging and cancer therapy simultaneously. Emerging nano‐delivery systems in cancer therapy still lack knowledge of the biological functions behind the interaction between nanoparticles and cancer cells. Since the potential of engineered nanoparticles addresses the various challenges, limiting the success of cancer therapy subsequently, it is a must to review the molecular targeting of a nano‐delivery system to enhance the therapeutic efficacy of cancer. This review focuses on using a nano‐delivery system, an imaging system, and encapsulated nanoparticles for cancer therapy. [ABSTRACT FROM AUTHOR]

Strong association has been recently observed between periodontitis/gingivitis and Oral squamous cell carcinoma (OSCC). A high incidence of oral cancer has been reported in the case of chronic periodontitis. Recently Cell cycle regulatory /Senescence genes have been associated with Gingivitis/ Periodontitis susceptibility. Cyclin D1 is one such cell cycle regulatory gene. Several findings have reported that Cyclin D1 (CCND1) G870A Single nucleotide polymorphism is associated with oral cancer (OC) risk, but yielded inconsistent data across different studies. This meta-analysis explores the precise relationship between CCND1 G870A polymorphism and OC risk. PubMed (Medline), EMBASE, & Google Scholar databases were searched for eligible studies and pooled odds ratios (ORs) and 95% confidence intervals (CI) were calculated. Newcastle-Ottawa analysis was done for selected articles quality assessment, bias in publication (if any) was estimated through Funnel plots and Egger’s test. Pooled analysis from eleven eligible studies suggests that CCND1 G870A polymorphism is not significantly associated with OC risk. Sub-group analysis by ethnicity failed to show any association. Sequential single study omission was performed to determine the credibility and resilience of the inferences drawn.

Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NFκB-2, TGF-β1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman’s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NFκB-2).

Background: Proprotein convertase subtilisin/kexin type-9 (PCSK-9) is a serine protease with profound effects on plasma LDL-C, the major risk factor for cardiovascular diseases (CVDs). However, plasma PCSK-9 level and its association with the biomarkers of CVDs, diabetes, and associated complications have not yet been reported in the northeastern population of India. Methods: Of the total cohort (n = 233), we analyzed healthy controls (HC; n = 50), freshly diagnosed type-2-diabetes mellitus (T2DM-FD; n = 46), T2DM treated (T2DM-T; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemia (T2DM-DL; n = 45) subjects. Plasma PCSK-9 and other biological determinants associated with T2DM, CVD, and nephrotic dysfunction were assessed. Results: The level of plasma PCSK-9 in HC, T2DM-FD, T2DM-T, T2DM-N, and T2DM-DL groups was found to be 184.1 ± 13.83, 183.1 ± 24.4.3, 241.8 ± 75.42, 403.7 ± 85.94, and 641.3 ± 135.5 ng/mL, respectively, indicating its role in the severity of the here-mentioned complications. Moreover, plasma PCSK-9 levels further showed a significant correlation with the biomarkers of hyperglycemia, particularly HbA1c, as well as LDL-C in T2DM-FD, T2DM-N, and T2DM-DL subjects of the Indian population, while moderate association in T2DM-T subjects. Conclusions: Our first-of-its-kind clinical study aiming to quantify the circulatory PCSK-9 level in the Indian population concluded that elevated PCSK-9 was significantly associated with the severity of diabetes and associated complications. Moreover, such elevation in PCSK-9 might be attributed to the lipid- and glucose-lowering medication-induced SREBP-2-dependent mechanisms. Since our conclusion is based on a pilot study, further cohort studies in larger populations of India are required to get a generalization regarding the role of PCSK-9 in DM and associated complications. [ABSTRACT FROM AUTHOR]

Cellulases are the enzymes of broad industrial interests due to their versatile applications including biomass conversion processing. However, issues, e.g., high production cost of enzyme and lack of suitable bioprocess technology, are the main thirst of this area. Additionally, fungal strains are frequently reported for the cost-effective cellulase and its constituent enzyme production, whereas narrow data are present on bacterial cellulase production. In this study, enhanced endoglucanase (EG) production has been investigated using bacterial strain Bacillus subtilis PF_1. Herein, EG has been produced using waste leaves of water hyacinth (WH), employed as substrate following solid state fermentation (SSF). At an optimum concentration of WH substrate (5.0 g), Bacillus subtilis PF_1 could produce 17 IU/gds EG and 12 IU/gds FP activity in 30 h. Besides, the enzyme activity was further enhanced by changing the particles texture, and maximum 21 IU/gds EG activity was noticed at 30 h in case of rough surface (RS) of WH as compared to smooth surface (SS) which produced only 9 IU/gds. Further, the crude EG enzyme exhibited an optimum incubation temperature of 60 °C at pH 5.0 when it was treated with TiO2 nanoparticles (NPs). Moreover, the same enzyme has shown its half-life stability at 60 °C for 4.5 h in the presence TiO2 NPs and the optimum incubation pH 5.0. The present study may have potential applications for cellulase production using WH which is imperative for numerous industrial purposes such as paper/pulp industries, biopolishing, and biomass conversion processing. [ABSTRACT FROM AUTHOR]

The current in-vivo study was premeditated to uncover the protective role of ezetimibe (EZ) against advanced glycation endproducts (AGEs)-related pathologies in experimental diabetes. Our results showed that EZ markedly improved the altered biochemical markers of diabetes mellitus (DM) (FBG, HbA1c, insulin, microalbumin, and creatinine) and cardiovascular disease (in-vivo lipid/lipoprotein level and hepatic HMG-CoA reductase activity) along with diminished plasma carboxymethyl-lysine (CML) and renal fluorescent AGEs level. Gene expression study revealed that EZ significantly down-regulated the renal AGEs-receptor (RAGE), nuclear factor-κB (NFκB-2), transforming growth factor-β (TGF-β1), and matrix metalloproteinase-2 (MMP-2) mRNA expression, however, the neuropilin-1 (NRP-1) mRNA expression was up-regulated. In addition, EZ also maintained the redox status via decreasing the lipid peroxidation and protein-bound carbonyl content (CC) and increasing the activity of high-density lipoprotein (HDL)-associated-paraoxonase-1 (PON-1) and renal antioxidant enzymes as well as also protected renal histopathological features. We conclude that EZ exhibits antidiabetic and reno-protective properties in diabetic rats. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MG) is a precursor for advanced glycation end-products (AGEs), which have a significant role in diabetes. The present study is designed to probe the immunological response of native and glycated low-density lipoprotein (LDL) in experimental animals. The second part of this study is to probe glycoxidative lesion detection in low-density lipoproteins (LDL) in diabetes subjects with varying disease duration. The neo-epitopes attributed to glycation-induced glycoxidative lesion of LDL in DM patients' plasma were, analyzed by binding of native and MG-modified LDL immunized animal sera antibodies using an immunochemical assay. The plasma purified human LDL glycation with MG, which instigated modification in LDL. Further, the NewZealand-White rabbits were infused with unmodified natural LDL (N-LDL) and MG-glycatedLDL to probe its immunogenicity. The glycoxidative lesion detection in LDL of DM with disease duration (D.D.) of 5–15 years and D.D. > 15 years was found to be significantly higher as compared to normal healthy subjects (NHS) LDL. The findings support the notion that prolonged duration of diabetes can cause structural alteration in LDL protein molecules, rendering them highly immunogenic in nature. The presence of LDL lesions specific to MG-associated glycoxidation would further help in assessing the progression of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Hyperglycemia is a poorly controlled diabetic condition, affects about 70% of people all round the world. In the year 2015, about 41.5 crore people were diabetic and is expected to reach around 64.3 crore by the year 2040. Cardiovascular diseases (CVDs) are considered as one of the major risk factors that cause more than half of the death of diabetic patients and promote related comorbidities. Atherosclerosis and amyloidosis are the prime factors linked with CVDs. Apolipoprotein A-I (ApoA-I) of HDL has protective action against CVDs, participates in reverse cholesterol transport mechanism and lipid metabolism, but gets easily glycated under prolonged hyperglycemic aura, i.e. glycation. ApoA-I has a potent role in maintenance of glucose level, providing a compelling link between diabetes and CVDs. Increased protein glycation in people with diabetes promotes atherosclerosis, which might play possible role in promotion of protein aggregation by altering the protein structure and its conformation. Here, we intend to investigate the mechanistic behavior of ApoA-I under the menace of glycation and its impact on ApoA-I structure and function that possibly link with aggregation or amyloidosis. [ABSTRACT FROM AUTHOR]

This study aims to describe the therapeutic potential of C. nocturnum leaf extracts against diabetes and neurological disorders via the targeting of α-amylase and acetylcholinesterase (AChE) activities, followed by computational molecular docking studies to establish a strong rationale behind the α-amylase and AChE inhibitory potential of C. nocturnum leaves-derived secondary metabolites. In our study, the antioxidant activity of the sequentially extracted C. nocturnum leaves extract was also investigated, in which the methanolic fraction exhibited the strongest antioxidant potential against DPPH (IC50 39.12 ± 0.53 µg/mL) and ABTS (IC50 20.94 ± 0.82 µg/mL) radicals. This extract strongly inhibited the α-amylase (IC50188.77 ± 1.67 µg/mL) and AChE (IC50 239.44 ± 0.93 µg/mL) in a non-competitive and competitive manner, respectively. Furthermore, in silico analysis of compounds identified in the methanolic extract of the leaves of C. nocturnum using GC-MS revealed high-affinity binding of these compounds with the catalytic sites of α-amylase and AChE, with binding energy ranging from −3.10 to −6.23 kcal/mol and from −3.32 to −8.76 kcal/mol, respectively. Conclusively, the antioxidant, antidiabetic, and anti-Alzheimer activity of this extract might be driven by the synergistic effect of these bioactive phytoconstituents. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa causes severe and chronic invasive infections in critically ill patients. Aminoglycosides are used either alone or in combination with β-lactams as effective agents for treating such infections (1). [...]

The objective of this study is to discover any possible association of gender or practitioner classification with orthodontic knowledge and attitudes towards orthodontic treatment. Descriptive cross-sectional research was conducted on two groups of dentists in the Ha'il region of Saudi Arabia. Group I included general practitioners, while Group II had non-orthodontic specialists. The findings suggest a statistically significant (p < 0.05) difference between the knowledge and attitudes of general practitioners and non-orthodontic specialists. Independent two tailed t-scores for difference in Knowledge (t-score = 3.19919, p = 0.003) and Attitude (t-score = 2.16314, p = 0.048319), highlight significant disparities in the knowledge and attitudes of general practitioners and non-orthodontic specialists. However, no statistically significant difference was observed in terms of knowledge and attitudes based on gender differences. This study captures and highlights subtle information that is very significant in dealing with critically important orthodontics issues. The study suggests that it is possible that a non-orthodontic specialist may suggest an altogether different line of treatment with different consequences when compared to a general practitioner and vice versa. This may result in unwanted, permanent orthodontic effects, highlighting the significance of the early stage of orthodontic treatment awareness. This research reveals disparities between the perceptions of general practitioners and non-orthodontic specialists about the stage and relevance of orthodontic treatment. It is strongly advised to see an orthodontic expert rather than a general practitioner or non-orthodontic specialist for orthodontic issues. [ABSTRACT FROM AUTHOR]

Cytokines are proteins that play a critical role in immune cells' development, maturation, and functional activities. For the first time, we have investigated the potential role of Terminalia arjuna as IL-4 and IL-13 modulators for preventing T1DM, i.e., autoimmune diabetes. It has been well documented that the stimulation of IL-4 and IL-13 can regulate the level of type 2 cytokines which can be maintained with the level of type 1 cytokines. The present study investigated gallic acid, arjunolic acid, luteolin, ellagic acid, and arjunone for their potential modulating activity of IL-4 and IL-13. The active amino acid residues identified for IL-4 are VAL51, HIS58, ASP87, THR30, GLN54, THR63, ARG64, LYS84, and GLU60. The active amino acid residues identified for IL-13 are H: GLU46, H: TRP47, H: GLN61, L: PHE98, L: VAL97, L: GLU162, L: THR163, H: ARG105, L: GLN38, L: ASP85, H: GLY42, L: GLY41, H: PRO41, H: TRP47, and L: PHE98. The phytoconstituents demonstrated better modulating activity towards IL-13 than IL-4. Luteolin displayed better potential for both IL-4 and IL-13, and therefore we concluded that it could be used to modulate the activity of IL-4 and IL-13 for the prevention of autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Glycation refers to carbonyl group condensation of the reducing sugar with the free amino group of protein, which forms Amadori products and advanced glycation end products (AGEs). These AGEs alter protein structure and function by configuring a negative charge on the positively charged arginine and lysine residues. Glycation plays a vital role in the pathogenesis of metabolic diseases, brain disorders, aging, and gut microbiome dysregulation with the aid of 3 mechanisms: (i) formation of highly reactive metabolic pathway-derived intermediates, which directly affect protein function in cells, (ii) the interaction of AGEs with its associated receptors to create oxidative stress causing the activation of transcription factor NF-κB, and (iii) production of extracellular AGEs hinders interactions between cellular and matrix molecules affecting vascular and neural genesis. Therapeutic strategies are thus required to inhibit glycation at different steps, such as blocking amino and carbonyl groups, Amadori products, AGEs-RAGE interactions, chelating transition metals, scavenging free radicals, and breaking crosslinks formed by AGEs. The present review focused on explicitly elaborating the impact of glycation-influenced molecular mechanisms in developing and treating noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose–protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications. [ABSTRACT FROM AUTHOR]

Biosynthetic procedure is one of the best alternatives, inexpensive and ecologically sound for the synthesis of titanium dioxide (TiO2) nanoparticles using a methanolic extract of medicinal plant. The main prospect of this study was to investigate the antiglycation activity of the TiO2 nanoparticles (TNP) prepared by ethanolic leaf extract of the Coleus scutellarioides. In this study, biosynthesized TNP characterized with UV‐Visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope. These TNP were further investigated with respect to their antiglycation property and it was checked in the mixture of d‐ribose glycated bovine serum albumin (BSA) by measuring ketoamine, carbonyl content, Advanced glycation end products (AGEs) and aggregation of protein instigated by glycation process. The inhibitory effect of TNP to restore the structure of BSA in presence of d‐ribose were also characterize by biophysical techniques mentioned above. Therefore, the findings of this study suggest repurposing of TNP for its antiglycation property that could be helpful in prevention of glycation instigated AGEs formation and structural loss of proteins. Significance statement: Provide a low cost green synthesis method for the synthesis of biologically active titanium dioxide (TiO2) nanoparticles.Provide the structural characterization of green synthesized TiO2 nanoparticles (TNP).An insight to identify the TNP as significant glycation inhibitor.Study suggest antiglycation potential detection of plant based TNP as possible therapeutic invention for hyperglycemia assisted diabetes and associated diseases. [ABSTRACT FROM AUTHOR]

The generation of advanced glycation end products (AGEs) through nonenzymatic protein glycation contributes to the pathogenesis of long‐lived diabetic problems. Metformin (MTF) is the very first drug having antihyperglycemic effects on type II diabetes mellitus which also possess interaction with dicarbonyl compounds and blocks the formation of AGEs. In the current study, MTF is bioconjugated with glycation‐derived synthesized gold nanoparticles (GNPs) of significant size. Additionally, using various biophysical and biochemical approaches, we investigated the antiglycating capacity MTF‐GNPs in contrast to MTF against d‐ribose‐derived glycation of bovine serum albumin. Our key findings via utilizing various assays demonstrated that MTF‐GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products, carbonyl content, hydxoxymethylfurfural content, production of fluorescent AGEs, normalizing the loss of secondary structure (i.e., α‐helix and β‐sheets) of proteins, elevating the levels of free lysine and free arginine more efficiently compared to pure MTF. Based on these results, we concluded that MTF‐GNPs possess a considerable antiglycation property and may be developed as an outstanding anti‐AGEs treatment drug. Further in vivo and clinical research are necessary to determine the therapeutic effects of MTF‐GNPs against AGE‐related and metabolic disorders. Highlights: Metformin is the first drug which interacts with dicarbonyl compounds and blocks the formation of AGEs.Metformin is bioconjugated with glycation‐derived synthesized gold nanoparticles (GNPs) of significant size.MTF‐GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products (EGEPs), carbonyl (CC), and Hydxoxymethylfurfural (HMF) content etc.MTF‐GNPs possess a considerable anti‐glycation property and may be developed as an outstanding anti‐AGEs treatment drug. Significance The key concluding of the current research demonstrates that the efficacy of the metformin (MTF) is enhanced by bioconjugating it with gold nanoparticles (MTF‐GNPs). Our findings also depict that MTF‐GNPs have higher antiglycation activity (utilized at lower doses) in contrast to the pure metformin antiglycation drug (utilized at higher doses, responsible for causing side‐effects in an individual). Therefore, MTF‐GNPs can be utilized as a promising anti‐AGE therapeutic drug (possessing high effectiveness and lower side effects) and, perhaps, diabetic problems in the future. [ABSTRACT FROM AUTHOR]

Anthocyanidins are the most abundant polyphenols in pomegranate juice. This class of molecules includes Delphinidin (Del), Cyanidin (Cya), and Pelargonidin (Pel). Using prostate, breast and pancreatic cancer cell lines PC3, MDA-MB-231, BxPC-3 and MiaPaCa-2, we show that anthocyanidins inhibit cell proliferation (measured by MTT assay) and induce apoptosis like cell death (measured by DNA/Histone ELISA). Copper chelator neocuproine and reactive oxygen species scavengers (thiourea for hydroxyl radical and superoxide dismutase for superoxide anion) significantly inhibit this reaction thus demonstrating that intracellular copper reacts with anthocyanidins in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitizes normal breast epithelial cells (MCF-10A) to Del-mediated growth inhibition as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters Ctr1 and ATP7A inMCF-10A cells, which is attenuated by the addition of Del in the medium. We propose that the copper mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of anthocyanidins. [ABSTRACT FROM AUTHOR]