Comparison of admission glycemic variability and glycosylated hemoglobin in predicting major adverse cardiac events among type 2 diabetes patients with heart failure following acute ST-segment elevation myocardial infarction.

Background and Objectives: Hyperglycemia is associated with adverse outcomes in patients with acute myocardial infarction (AMI) as well as in patients with heart failure. However, the significance of admission glycemic variability (GV) in predicting outcomes among diabetes patients with heart failure (HF) following acute ST-segment elevation myocardial infarction (ASTEMI) remains unclear. This study aims to explore the prognostic value of admission GV and admission glycosylated hemoglobin (HbA1c) levels in individuals diagnosed with type 2 diabetes and HF following ASTEMI. Methods: We measured GV and HbA1c upon admission in 484 consecutive patients diagnosed with type 2 diabetes and HF following ASTEMI. GV, indicated as the mean amplitude of glycemic excursions (MAGE), was assessed utilizing a continuous glucose monitoring system (CGMS). admission MAGE values were categorized as < 3.9 or ≥ 3.9 mmol/L, while HbA1c levels were classified as < 6.5 or ≥ 6.5%. Participants were followed up prospectively for 12 months. The relationship of admission MAGE and HbA1c to the major adverse cardiac event (MACE) of patients with type 2 diabetes and HF following ASTEMI was analyzed. Results: Among the 484 enrolled patients, the occurrence of MACE differed significantly based on MAGE categories (< 3.9 vs. ≥ 3.9 mmol/L), with rates of 13.6% and 25.3%, respectively (P = 0.001). While MACE rates varied by HbA1c categories (< 6.5 vs. ≥ 6.5%) at 15.7% and 21.8%, respectively (P = 0.086). Patients with higher MAGE levels exhibited a notably elevated risk of cardiac mortality and an increased incidence of HF rehospitalization. The Kaplan-Meier curves analysis demonstrated a significantly lower event-free survival rate in the high MAGE level group compared to the low MAGE level group (log-rank test, P < 0.001), while HbA1c did not exhibit a similar distinction. In multivariate analysis, high MAGE level was significantly associated with incidence of MACE (hazard ratio 3.645, 95% CI 1.287-10.325, P = 0.015), whereas HbA1c did not demonstrate a comparable association (hazard ratio 1.075, 95% CI 0.907-1.274, P = 0.403). Conclusions: Elevated admission GV emerges as a more significant predictor of 1-year MACE in patients with type 2 diabetes and HF following ASTEMI, surpassing the predictive value of HbA1c.

HbA1c variability associated with dementia risk in people with type 2 diabetes.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long-term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. HIGHLIGHTS: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years). This cohort was based in Northern California between 1996 and 2018. We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk. Greater HbA1c variability was associated with greater dementia hazard. This was most evident among those with normal-low mean HbA1c concentrations.

Nonpharmacological interventions on glycated haemoglobin in youth with type 1 diabetes: a Bayesian network meta-analysis.

The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI -  1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI -  1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.

Development of an indirect ELISA for the immunoprotection evaluation of E2 antibodies against classical swine fever virus.

The Chinese government's reclassification of Classical Swine Fever (CSF) from a class Ⅰ to a class Ⅱ animal infectious disease, now also including CSF under the disease eradication program, reflects the significant progress made through extensive immunization with CSF vaccines. In light of this advancement, there is an imperative need for an expedient and accurate method to assess the levels of immunoprotection against classical swine fever virus (CSFV) in vaccinated pigs, a critical component in the campaign to eradicate the disease. This study develops an indirect enzyme-linked immunosorbent assay (iELISA) based on a highly glycosylated E2 protein stable expressed in CHO-K1 mammalian cells. Statistical analysis revealed strong positive correlations between the iELISA and VNT results (r = 0.9063, p < 0.0001) that were much greater than those between the IDEXX ELISA and VNT results (r = 0.8126, p < 0.0001). Taking the VNT data as the standard, the consistency of the iELISA (κ =0.880) was greater than that of the IDEXX ELISA (κ =0.699). In summary, the iELISA provides a more efficient and precise method for assessing CSFV immunity in pigs. Its reliable detection of immunoprotection levels against CSFV makes it an essential tool for optimizing CSF vaccination strategies. Consequently, its application can significantly support the ongoing efforts to eradicate CSF.

Lectins as a promising therapeutic agent for breast cancer: A review.

Efficient treatment of cancer has been a subject of research by scientists for many years. Current treatments for cancer, such as radiotherapy, chemotherapy and surgery have been used in traditional combination therapy, but they have major setbacks like non-specificity, non-responsiveness in certain cancer types towards treatment, tumor recurrence, etc. Epidemiological data has shown that breast cancer accounts for 14% of cancer cases occurring in Indian women. In recent years, scientists have started to focus on the use of natural compounds like lectins obtained from various sources to counter the side effects of traditional therapy. Lectins like Sambucus nigra Agglutinin, Maackia amurensis lectin, Okra lectins, Haliclona caerulea lectin, Sclerotium rolfsii lectin, etc., have been discovered to have both diagnostic and therapeutic potential for breast cancer patients. Lectins have been found to have inhibitory effects on various cancer cell activities such as neo-angiogenesis, causing cell cycle arrest at the G1 phase, and inducing apoptosis. The major idea behind the use of lectins in cancer diagnostics and therapeutics is their capability to bind to glycosylated proteins that are expressed on the cell surface. This review focuses on an exploration of the roles of post-translational modification in cancer cells, especially glycosylation, and the potential of lectins in cancer diagnosis and therapeutics.

Efficacy of telemedicine intervention in the self-management of patients with type 2 diabetes: a systematic review and meta-analysis.

Purpose: We aimed to report the latest and largest pooled analyses and evidence updates to assess the effectiveness of telemedicine interventions for self-management (DSM) in patients with type 2 diabetes mellitus (T2DM). Methods: A systematic literature search was conducted using PubMed, Cochrane, Embase, and Web of Science in December 2023. We included randomized controlled trials (RCTs) of adults (≥18 years of age) diagnosed with T2DM where the intervention was the application of telemedicine. The Cochrane Risk of Bias Assessment was used to evaluate quality. The study's main outcome indicators were glycosylated hemoglobin (HbA1c) and diabetes self-management (DSM) capacity. Results: A total of 17 eligible articles, comprising 20 studies and 1,456 patients (734 in the intervention group and 722 in the control group), were included in the evidence synthesis. The baseline characteristics of both groups were similar in all outcomes. Comprehensive analyses showed post-intervention decreases in HbA1c, 2-h postprandial glucose, systolic and diastolic blood pressure, increases in Diabetes Self- Care activities, DSM competencies based on dietary and medication adherence, and improvements in overall DSM scores, all of which were statistically significant. While no statistically significant differences were observed in body mass index, lipids, and other DSM dimensions. Based on subgroup analyses, app-based experimental interventions targeting under 60 years old populations in Asia and North America were found to be more effective and less heterogeneity in the short term (<6 months of intervention). Conclusion: Telemedicine interventions may assist patients with T2DM in enhancing their DSM and improving their HbA1c levels. Clinician can use various telemedicine interventions to enhance DSM in T2DM patients, considering local circumstances. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42024508522.

Immunoglobulin A vasculitis: The clinical features and pathophysiology.

Palpable purpura, gastrointestinal symptoms, joint involvement, and renal disease characterize immunoglobulin A vasculitis (IgAV). Renal involvement ranging from mild proteinuria to severe nephritic or nephrotic syndrome highlights the importance of monitoring kidney function in patients with IgAV. Recognizing these key features is crucial for early diagnosis and appropriate management to prevent long-term complications related to kidney disease. However, the pathogenesis of IgAV remains unclear. Disease mechanisms involve various factors, including the interplay of aberrantly glycosylated IgA, anti-endothelial cell antibodies, and neutrophils following infection triggers, which are the main pathogenic mechanisms of IgAV. Insights from cases of IgAV related to Coronavirus disease 2019 have offered additional understanding of the connection between infection and IgAV pathogenesis. This review provides a valuable resource for healthcare professionals and rheumatology researchers seeking a better understanding of the clinical features and pathophysiology of IgAV.

Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition of Metastatic Phenotype.

Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.

Relationship of urinary glyphosate concentrations with glycosylated hemoglobin and diabetes in US adults: a cross-sectional study.

BACKGROUND: Glyphosate is a commonly used herbicide worldwide and is purportedly associated with multiple health effects. Research assessing the association of glyphosate concentrations with glycosylated hemoglobin (HbA1c) levels and the prevalence of diabetes is scarce. We sought to evaluate the association between urinary glyphosate levels and HbA1c levels and the prevalence of diabetes. METHODS: A total of 2,745 adults in the National Health and Nutrition Examination Survey from 2013 to 2016 were included in this study. Generalized linear models (GLM) were applied to evaluate the associations of glyphosate concentrations with HbA1c levels and the prevalence of diabetes. The dose-response relationship was examined using restricted cubic splines (RCS). RESULTS: Significantly positive correlations of urinary glyphosate concentrations with HbA1c levels (percentage change: 1.45; 95% CI: 0.95, 1.96; P < 0.001) and the prevalence of diabetes (OR: 1.45; 95% CI: 1.24, 1.68; P < 0.001) were found after adjustment. Compared with the lowest quartile of glyphosate levels, the highest quartile was positively associated with HbA1c levels (percentage change: 4.19; 95% CI: 2.54, 5.85; P < 0.001) and the prevalence of diabetes (OR: 1.89; 95% CI: 1.37, 2.63; P < 0.001). The RCS curves demonstrated a monotonically increasing dose-response relationship between urinary glyphosate levels and the prevalence of diabetes and HbA1c levels. CONCLUSIONS: Urinary glyphosate concentrations are positively associated with HBA1c levels and the prevalence of diabetes. To verify our findings, additional large-scale prospective investigations are required.

Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics.

Glycosylated nanoplatforms have emerged as promising tools in the field of cancer theranostics, integrating both therapeutic and diagnostic functionalities. These nanoscale platforms are composed of different materials such as lipids, polymers, carbons, and metals that can be modified with glycosyl moieties to enhance their targeting capabilities towards cancer cells. This review provides an overview of different modification strategies employed to introduce glycosylation onto nanoplatforms, including chemical conjugation, enzymatic methods, and bio-orthogonal reactions. Furthermore, the potential applications of glycosylated nanoplatforms in cancer theranostics are discussed, focusing on their roles in drug delivery, imaging, and combination therapy. The ability of these nanoplatforms to selectively target cancer cells through specific interactions with overexpressed glycan receptors is highlighted, emphasizing their potential for enhancing efficacy and reducing the side effects compared to conventional therapies. In addition, the incorporation of diagnostic components onto the glycosylated nanoplatforms provided the capability of simultaneous imaging and therapy and facilitated the real-time monitoring of treatment response. Finally, challenges and future perspectives in the development and translation of glycosylated nanoplatforms for clinical applications are addressed, including scalability, biocompatibility, and regulatory considerations. Overall, this review underscores the significant progress made in the field of glycosylated nanoplatforms and their potential to revolutionize cancer theranostics.

Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation.

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H-1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

Impact of Lifestyle Modification: An Intervention on Newly Diagnosed Diabetics of the Urban Slum of Meerut.

Introduction Diabetes is a long-term condition that necessitates ongoing medical attention and self-care to prevent immediate complications and minimize the likelihood of long-term issues. Early diagnosis is one of the most important steps for people living with diabetes to take. Public awareness regarding the importance of lifestyle modification in managing type 2 diabetes mellitus is a crucial preventive measure. Despite continuous efforts to raise public awareness, the prevalence of type 2 diabetes continues to increase, with most people overlooking the importance of a healthy lifestyle. Our goal was to assess the impact of lifestyle modification on glycemic control in newly diagnosed diabetic patients. Materials and methods A total of 503 adults aged 30 years and above who were nondiabetic or were unaware of their diabetic status were assessed for their fasting blood glucose levels. Individuals identified as diabetic based on their fasting blood glucose levels were subjected to lifestyle modification for a period of three months. Glycemic levels were measured at the beginning and the end of the study period for comparison. Results Of the study participants, 7.6% were undiagnosed diabetics with increased blood sugar levels who were unaware of their diabetic status. Mean anthropometric measurements from pre- to postintervention values improved overall. Overall reduction was observed in weight (66.21±12.97 to 63.18±11.48), waist circumference (96.21±13.01 to 91.77±11.82), hip circumference (105.16±11.91 to 103.58±10.88), waist-hip ratio (0.91±0.09 to 0.88±0.08) and body mass index (27.48±6.04 to 26.18±5.30). Significant reductions were observed in the mean glycemic values, including fasting blood sugar (180.19±55.81 to 152.56±45.74) and glycosylated hemoglobin levels (8.61±1.97 to 6.68±1.67). Conclusion Lifestyle modification plays a crucial role in managing diabetes, both in preventing its onset and controlling its progression. The present study highlights the importance of early diagnosis and lifestyle interventions in the management of diabetes, thereby stressing the necessity of comprehensive strategies to combat this situation.

Revealing the mechanism of the lutein protective function of epicatechin-fructan glycosylated soybean protein isolate.

Lutein possesses various physiological activities but is susceptible to light degradation, thermal degradation, and oxidative degradation. As such, protecting the activity of lutein-based products using natural extracts has become a current research. In this study, lutein was protected by complexing inulin-type fructan (ITF), soybean protein isolate (SPI), and epicatechin (EC), and the protection mechanism of epicatechin-fructan glycosylated soybean protein isolate (EC-GSPI) toward lutein was elucidated comprehensively. The results showed that the addition of EC delayed the degradation of lutein. The results of light stability experiments showed that increased EC significantly enhanced the storage time of the GSPI-Lutein system from 4 to 13 days. Additionally, the effect of EC on glycosylated soybean 7S globulin (G7S) and glycosylated soybean 11S globulin (G11S) was assessed. The light stability of G11S-Lutein and G7S-Lutein after the addition of EC was from G11S > G7S → G7S > G11S. Furthermore, the proteins purified from SPI interacted differently with EC and ITF, with soybean 7S globulin (7S) mainly interacting with EC and soybean 11S globulin (11S) mainly interacting with ITF. EC-GSPI-Lutein exhibited a good protective effect, probably due to the occurrence of hygrothermal Maillard between ITF and 11S, providing a porous structure for lutein storage. At the same time, the binding of EC to 7S significantly enhanced the antioxidant property of the solution and the stability of the protein secondary structure, thereby prolonging the storage time of lutein.

Escherichia coli and Pichia pastoris: microbial cell-factory platform for -full-length IgG production.

Owing to the unmet demand, the pharmaceutical industry is investigating an alternative host to mammalian cells to produce antibodies for a variety of therapeutic and research applications. Regardless of some disadvantages, Escherichia coli and Pichia pastoris are the preferred microbial hosts for antibody production. Despite the fact that the production of full-length antibodies has been successfully demonstrated in E. coli, which has mostly been used to produce antibody fragments, such as: antigen-binding fragments (Fab), single-chain fragment variable (scFv), and nanobodies. In contrast, Pichia, a eukaryotic microbial host, is mostly used to produce glycosylated full-length antibodies, though hypermannosylated glycan is a major challenge. Advanced strategies, such as the introduction of human-like glycosylation in endotoxin-edited E. coli and cell-free system-based glycosylation, are making progress in creating human-like glycosylation profiles of antibodies in these microbes. This review begins by explaining the structural and functional requirements of antibodies and continues by describing and analyzing the potential of E. coli and P. pastoris as hosts for providing a favorable environment to create a fully functional antibody. In addition, authors compare these microbes on certain features and predict their future in antibody production. Briefly, this review analyzes, compares, and highlights E. coli and P. pastoris as potential hosts for antibody production.

Risk Factors for Urinary Tract Infection in Elderly Patients with Type 2 Diabetes: A Retrospective Cohort Study.

OBJECTIVE: The risk factors of urinary tract infection in elderly patients with type 2 diabetes were investigated. METHODS: A total of 72 elderly patients admitted to our hospital from December 2019 to September 2023 because of with type 2 diabetes were retrospectively included. They were divided into the observation group (n = 35) and control group (n = 37) according to whether they had urinary tract infection. The general clinical data, clinical characteristics and the distribution of pathogenic bacteria in the observation group were collected and analysed. Then, t-tests, chi-square tests, regression analysis and receiver operating characteristic curve analysis were conducted. RESULTS: Escherichia coli (E. coli) accounted for 51.43% of the pathogenic bacteria in the observation group, whereas Klebsiella pneumoniae (K. pneumoniae) accounted for 22.86%. The remaining pathogens accounted for 2.86% each. Differences in gender, course of disease, glycosylated haemoglobin and comorbid urinary calculi were found between the groups (p < 0.05); These factors were all risk factors for concurrent urinary infection, and the odds ratios were all >1. The obtained values for gender, disease course, glycosylated haemoglobin and comorbid urinary calculi were respectively 0.594, 0.654, 0.738 and 0.696 (area under the curve); 0.971, 0.714, 0.800 and 0.743 (sensitivity); 0.216, 0.595, 0.676 and 0.649 (specificity); And 0.188, 0.309, 0.476 and 0.392 (Youden index). CONCLUSIONS: Common pathogens in elderly people with type 2 diabetes and comorbid urinary tract infection are E. coli and K. pneumoniae. Risk factors include gender, disease duration, glycosylated haemoglobin and urinary stones. The prompt identification of pathogens and risk factors facilitates clinical treatment, reducing infection incidence.

Evaluation of Glycosylated Hemoglobin Levels and Effect of Tobacco Smoking in Periodontally Diseased Non-Diabetic Patients.

Background and Objective: Chronic diseases have progressively increased worldwide, impacting all areas and socioeconomic groups. Periodontal disease is an increasing global concern and contains risk factors similar to other chronic illnesses. The main risk factor for periodontitis is smoking. Smoking not only hastens periodontal disease but also complicates periodontal therapy. Serum glycosylated hemoglobin levels, which are derived from the average life span of an erythrocyte, are a good indicator of glycemic management during the preceding one to three months. This study was undertaken to assess the association between tobacco smoking and periodontal disease by evaluating plaque score, gingival score, extent and severity index (ESI), and glycemic status by estimating serum HbA1c in cigarette smoker patients compared to non-smokers. Methods: The study was conducted with 40 patients in the age range of 20-40 years. Patients were divided into two groups: non-smokers (Group I) and cigarette smokers (Group II). Periodontal clinical parameters such as the plaque index (PI), gingival index (GI), and ESI were recorded during the oral cavity examination. The biochemical marker, serum glycosylated hemoglobin, was measured in both groups. All parameters were measured at baseline and three months after periodontal therapy. The statistical tests used were the paired t-test, and Chi-square test for comparison between both groups. Results: The mean difference of PI of non-smokers was 0.33 ± 0.30, and smokers were 0.52 ± 0.32, which was statistically significant. The mean difference of GI of non-smokers was 0.34 ± 0.19 and smokers 0.36 ± 0.303, which was statistically significant. The mean difference of extent in non-smokers was 5.33 ± 1.59, 5.52 ± 2.43, and smokers were 0.18 ± 0.17. The mean difference in severity in non-smokers was 0.18 ± 0.17, and smokers were 0.31 ± 0.25, which was statistically significant. The mean difference of HbA1c in non-smokers and smokers was 0.43 ± 0.277 and 0.415 ± 0.230, which shows a higher mean difference in non-smokers, which was statistically non-significant. Conclusion and Global Health Implications: This study concluded that each of Group I and Group II showed substantial improvements in all clinical periodontal variables, which include plaque index (PI), gingival index (GI), extent and severity index (ESI), and biochemical marker serum glycosylated hemoglobin. Controlling inflammation with SRP can improve insulin resistance, lower glucose levels, and prevent non-enzymatic glycation of hemoglobin.

Recombinant human fibroblast growth factor 7 obtained from stable Chinese hamster ovary cells enhances wound healing.

Although fibroblast growth factor 7 (FGF7) is known to promote wound healing, its mass production poses several challenges and very few studies have assessed the feasibility of producing FGF7 in cell lines such as Chinese hamster ovary (CHO) cells. Therefore, this study sought to produce recombinant FGF7 in large quantities and evaluate its wound healing effect. To this end, the FGF7 gene was transfected into CHO cells and FGF7 production was optimized. The wound healing efficacy of N-glycosylated FGF7 was evaluated in animals on days 7 and 14 post-treatment using collagen patches (CPs), FGF7-only, and CP with FGF7 (CP+FGF7), whereas an untreated group was used as the control. Wound healing was most effective in the CP+FGF7 group. Particularly, on day 7 post-exposure, the CP+FGF7 and FGF7-only groups exhibited the highest expression of hydroxyproline, fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor. Epidermalization in H&E staining showed the same order of healing as hydroxyproline content. Additionally, the CP+FGF7 and FGF7-only group exhibited more notable blood vessel formation on days 7 and 14. In conclusion, the prepared FGF7 was effective in promoting wound healing and CHO cells can be a reliable platform for the mass production of FGF7.

The crane fly glycosylated triketide δ-lactone cornicinine elicits akinete differentiation of the cyanobiont in aquatic Azolla fern symbioses.

The restriction of plant-symbiont dinitrogen fixation by an insect semiochemical had not been previously described. Here we report on a glycosylated triketide δ-lactone from Nephrotoma cornicina crane flies, cornicinine, that causes chlorosis in the floating-fern symbioses from the genus Azolla. Only the glycosylated trans-A form of chemically synthesized cornicinine was active: 500 nM cornicinine in the growth medium turned all cyanobacterial filaments from Nostoc azollae inside the host leaf-cavities into akinetes typically secreting CTB-bacteriocins. Cornicinine further inhibited akinete germination in Azolla sporelings, precluding re-establishment of the symbiosis during sexual reproduction. It did not impact development of the plant Arabidopsis thaliana or several free-living cyanobacteria from the genera Anabaena or Nostoc but affected the fern host without cyanobiont. Fern-host mRNA sequencing from isolated leaf cavities confirmed high NH4-assimilation and proanthocyanidin biosynthesis in this trichome-rich tissue. After cornicinine treatment, it revealed activation of Cullin-RING ubiquitin-ligase-pathways, known to mediate metabolite signaling and plant elicitation consistent with the chlorosis phenotype, and increased JA-oxidase, sulfate transport and exosome formation. The work begins to uncover molecular mechanisms of cyanobiont differentiation in a seed-free plant symbiosis important for wetland ecology or circular crop-production today, that once caused massive CO2 draw-down during the Eocene geological past.

Glycemic control and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: insight from ventricular remodeling using cardiac MRI.

BACKGROUND: Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. METHODS: A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c < 6.5% (intensive control), HbA1c 6.5-7.5% (modest control), and HbA1c > 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. RESULTS: Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c < 6.5%: hazard ratio (HR) = 2.42, 95% confidence interval (CI) = 1.07-5.45; P = 0.033; HbA1c > 7.5%: HR = 2.24, 95% CI = 1.01-4.99; P = 0.038] and secondary outcomes (HbA1c < 6.5%: HR = 2.84, 95% CI = 1.16-6.96; P = 0.022; HbA1c > 7.5%: HR = 2.65, 95% CI = 1.08-6.50; P = 0.038) compared with those in the middle HbA1c category. CONCLUSIONS: We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.

A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861.

BACKGROUND: Treatment with tumor-targeted toxins attempts to overcome the disadvantages of conventional cancer therapies by directing a drug's cytotoxic effect specifically towards cancer cells. However, success with targeted toxins has been hampered as the constructs commonly remain bound to the outside of the cell or, after receptor-mediated endocytosis, are either transported back to the cell surface or undergo degradation in lysosomes. Hence, solutions to ensure endosomal escape are an urgent need in treatment with targeted toxins. In this work, a molecular adapter that consists of a cell penetrating peptide and two cleavable peptides was inserted into a targeted toxin between the ribosome-inactivating protein dianthin and the epidermal growth factor. Applying cell viability assays, this study examined whether the addition of the adapter further augments the endosomal escape enhancement of the glycosylated triterpenoid SO1861, which has shown up to more than 1000-fold enhancement in the past. RESULTS: Introducing the peptide adapter into the targeted toxin led to an about 12-fold enhancement in the cytotoxicity on target cells while SO1861 caused a 430-fold increase. However, the combination of adapter and glycosylated triterpenoid resulted in a more than 4300-fold enhancement and in addition to a 51-fold gain in specificity. CONCLUSIONS: Our results demonstrated that the cleavable peptide augments the endosomal escape mediated by glycosylated triterpenoids while maintaining specificity. Thus, the adapter is a promising addition to glycosylated triterpenoids to further increase the efficacy and therapeutic window of targeted toxins.