High Glucose Levels Research Articles

Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1. In those species not able to synthesize ascorbate and expressing Glut-1 on erythrocytes virus could interact with Glut-1 or other functionally related protein, and the influx of glucose into the cells would be severely impaired. As a consequence, transient hyperglycemia and a marked oxidative stress coupled with the high levels of glucose in plasma would be established, and then promote the activation of NF–κB transcription, exacerbating a pro-inflammatory response mediated by cytokines and chemokines: The inability to synthesize ascorbate is an Achilles Heel when trying to counteract the oxidative stress.

Expanding access to non-communicable disease screening in war-affected communities in Ukraine

Abstract Background Non-communicable diseases (NCDs) account for 91% of premature deaths in Ukraine. However, NCD screening lags among young people and across the entire population. The ongoing war has exacerbated barriers to NCD screening due to damaged infrastructure, understaffed medical facilities, and health system deterioration. Intervention/response To improve screening, diagnosis, and care, in March 2023 the PATH-led, USAID-funded Support TB Control Efforts in Ukraine (STBCEU) project established community level health access points (HAPs) in five conflict-affected communities. STBCEU procured screening tools (tannometers, glucometers, portable ECGs) for common NCDs, printed informational materials, trained 143 specialists, designed a reporting system, and facilitated monitoring visits to 77 HAPs. Results By the end of 2023, the project equipped 113 HAPs in the five communities, and 102 of them initiated NCD screening. From January-March 2024, 1,694 people under 40 years old were screened for NCDs. Among 1,488 blood pressure measurements, 143 cases had high readings (9.6 ±1.5%), 90 (62.9%) of which were first-time diagnoses, and 53 (37.1%) treatment monitoring. Glucose levels were measured 809 times, with elevated levels in 44 cases (5.4 ±1.5%), 30 (68.2%) of which were first-time diagnoses, and 14 (31.8%) treatment monitoring. Additionally, 1,144 mental health consultations were provided. Conclusions This initiative represented a first in Ukraine: per national requirements, young people have not historically been screened for NCDs. Expanding NCD screening in war-affected communities has demonstrated substantial early success, with significant detection of high blood pressure and elevated glucose levels among people under 40. This proactive, cost-effective intervention underscores the need for accessible, community-level health interventions in crisis settings and showcases a scalable model for integrating NCD screening into emergency health response frameworks. Key messages • The implementation of community-level NCD screening has shown early success in detecting high blood pressure and elevated glucose levels among people under 40. • Cost-effective NCD screening underscores the need for accessible, community health interventions, providing a scalable model for integrating NCD screening into emergency health response.

Higher blood glucose within the first 72 hours after prolonged cardiac arrest predict poor prognosis: a post-hoc analysis of Prague OHCA trial

Abstract Background and purpose Both low and higher glucose levels and their tight control were associated with worse prognosis of critically ill patients. We performed a post-hoc analysis of treated Prague OHCA trial population of patients subjected to extracorporeal cardiopulmonary resuscitation (ECPR) vs. standard approach for refractory cardiac arrest, aimed to assess relationship of glucose levels in the first 72 hours after admission to the neurological outcome. Methods Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this post-hoc analysis, the effects blood glucose on the best cerebral performance category (CPC) within 180 days was examined. Blood samples for glycemia evaluation were drawn at admission and then every 3 hours within the first 3 days. Fischer exact test was used to analyze the impact on the prognosis (CPC 1-2 = good and CPC 3-5 = poor prognosis). Results Patients with CPC 1-2 did not differ in blood glucose on admission from patients with CPC 3-5. However, patients with type 2 diabetes mellitus had significantly worse prognosis (83 vs. 60% of diabetics vs. non-diabetics had poor prognosis, p = 0.007). Glycemia on admission was slightly but significantly related to the amount of given epinephrine and to the serum triglycerides. Patients having at least 3 glucose levels >10 mmol/L within the first 72 hours had worse neurological prognosis: CPC 1-2 was reached in 61.4% of patients with less than 3 levels >10 mmol/L, but only in 24% of patients that fulfilled this criterion (p=0.000004). Conclusions Repeatedly higher blood glucose within the first 72 hours after admission for prolonged cardiac arrest are related to worse prognosis.

Epigenetic modulation of sirt1 and sirt6 in cardiovascular diseases: unraveling autophagy regulation and endothelial function

Abstract Background Heart failure (HF) and cardiovascular diseases (CVD) still represent major causes of death. Dysmetabolic conditions led by epigenetic alterations play a major role as CVD triggers, expecially those related to the modulation and control of autophagy during the remodelling in HF. Accordingly, several studies have strengthened the role of epigenetics in regulating both cardiac/endothelial phenotype and function, demonstrating how sirtuins, a well-acknowledged family of histone deacetylase, can conjunct the control of cardiac fibrosis, angiogenesis and induction of autophagy. However, this link remains to be fully clarified and explored. Thus, novel drugs targeting autophagy trough epigenetic mechanisms are considered appealing as targets from a pharmacological standpoint in CVD. Purpose This project aims to develop and test two epigenetic modulators and allosteric activators targeting SIRT1 and -6 to further elucidate their role in autophagy regulation and in cardiac/endothelial biology. Methods Chemical synthesis of SIRT1 and SIRT6 activator isoform (SRT2104 and MDL800). Evaluation of epigenetic modulation (H3 histone acetylation H3K9) of endothelial cells (HUVEC). HUVEC survival, angiogenic and autophagy activity were assessed undergo hyperglycemic or hypoxic stress, co-treatment with the selected compounds. Results The specific activator of SIRT-1 (SRT2104) and SIRT-6 (MDL800) show epigenetic activity as they induce the deacetylation of histone H3 on lysine 9. Endothelial cell viability is not influenced by the treatment with both modulators in hyperglycemia and upon hypoxic condition. In HUVEC cultures underwent to hyperglycemia-based stress, both molecules can activate autophagy with an increase in LC3 II protein (1,4-fold HG SRT2104 and 2,8-fold HG MDL800), compared to control.The treatment with SRT2104 enhances HUVEC tube formation, suggesting the increased functional angiogenic ability even in presence of high levels of glucose. Interestingly, the treatment with SRT2104 impacts the transcriptional levels of other members of the sirtuins family, by increasing SIRT-2, 3 and 5. In conclusion, the epigenetic activators SRT2104 and MDL800 have a beneficial effect on endothelial cells by enhancing the autophagic process and stimulate neoangiogenesis.The implementation of these results will attempt to understand to what extent epigenetic drugs such as sirtuin activators, could boost the more pleiotropic and less targeted effects of the current cardiovascular drugs, and to evaluate their functional and phenotype-driven drug refinement.

Immunomodulatory activity of kersen leaf extract (Muntingia calabura) on diabetic rats: analysis of immune response

The immune response to high blood glucose levels leads to an inflammatory response and also produces inflammation mediators. Immunomodulatory functions of Kersen (Muntingia calabura) need further enhancement to ensure that its benefits are more widely recognized by the public. This study aims to determine the immunomodulatory activity of Kersen leaf in inducing and modulating the immune response in diabetic rats. This study was an experimental laboratory with a pre-and post-test with a control group design. The subjects were 30 white rats (Rattus Novergicus Wistar Strain), were treated with extract M. calabura dose 1 (100 mg/kg bw/day), dose 2 (200 mg/kg bw/day), dose 3 (300 mg/kg bw/day). For clinical evaluation, three control groups were formed, including a Normal Control Group, a Diabetes Mellitus (DM) Positive Group, and a DM Positive Group treated with Anti-Diabetic Drugs. The highest amount of IFN-γ concentrations were found in the DM positive control group + antidiabetic drugs (710.3 ± 27.2 ng/mL). The highest number of Nitrit Oxide (NO) concentration was found in the DM positive control group (103.7 ± 10.2 µmol/L). The highest average amount of pancreatic β cell regeneration was found in the normal control group. The DM positive control group and the treatment group had a significant difference (p < 0.05) It means that there is a significant difference in the data of all treatment groups, or these three groups have anti-diabetic activity by repairing or preventing damage to the pancreas organ in DM rats. This study revealed that M. calabura possesses immunomodulatory activity, capable of inducing and modulating immune responses in diabetic rats.

High glucose combined with lipopolysaccharide stimulation inhibits cell proliferation and migration of human HaCaT keratinocytes by impacting redox homeostasis and activating the polyol pathway.

High glucose level and chronic inflammation are characteristic features of diabetic cutaneous wounds. Keratinocytes make up the epidermis and play an important role in skin repair. However, metabolomic changes of keratinocytes in chronic diabetic ulcers have not been fully studied. This study used high levels of glucose combined with lipopolysaccharide to treat human HaCaT keratinocytes. Untargeted metabolomic combined with colorimetric assays were used to explore the changes of keratinocyte metabolites and related metabolic pathways caused by high glucose and lipopolysaccharide. Results demonstrated that high glucose combined with lipopolysaccharide treatment increased intracellular reactive oxygen species and impaired proliferation and migration of keratinocytes. Untargeted metabolomics analysis identified a total of 273 differential metabolites. Redox metabolism associated metabolites were largely altered. Reduced nicotinamide adenine dinucleotide, gamma-glutamylcysteine, superoxide dismutase activity and SOD2 gene expression were significantly upregulated while nicotinamide adenine dinucleotide, glutathione, glutathione peroxidase, several types of lysophosphatidylcholine, lysophosphatidylinositol, and GPR55 gene expression were downregulated. Alterations of glutathione and nicotinamide adenine dinucleotide were verified by colorimetric assays. For the first time, high glucose and LPS were observed to boost the levels of fructose, aldose reductase and sorbitol dehydrogenase of the polyol pathway in HaCaT cells. Further treatment of HaCaT with fructose leading to inhibition of cell proliferation and migration. Our data suggest high glucose combined with lipopolysaccharide significantly altered redox homeostasis associated metabolites and activate the polyol pathway in keratinocytes to impact cell proliferation and migration, providing new strategies for the treatment of chronic diabetic ulcers.

Exploring cutting-edge approaches in diabetes care: from nanotechnology to personalized therapeutics.

Diabetes mellitus (DM) is a persistent condition characterized by high levels of glucose in the blood due to irregularities in the secretion of insulin, its action, or both. The disease was believed to be incurable until insulin was extracted, refined, and produced for sale. In DM, insulin delivery devices and insulin analogs have improved glycemic management even further. Sulfonylureas, biguanides, alpha-glucosidase inhibitors, and thiazolidinediones are examples of newer-generation medications having high efficacy in decreasing hyperglycemia as a result of scientific and technological advancements. Incretin mimetics, dual glucose-dependent insulinotropic polypeptide, GLP-1 agonists, PPARs, dipeptidyl peptidase-4 inhibitors, anti-CD3 mAbs, glucokinase activators, and glimins as targets have all performed well in recent clinical studies. Considerable focus was placed on free FA receptor 1 agonist, protein tyrosine phosphatase-1B inhibitors, and Sparc-related modular calcium-binding protein 1 which are still being studied. Theranostics, stem cell therapy, gene therapy, siRNA, and nanotechnology are some of the new therapeutic techniques. Traditional Chinese medicinal plants will also be discussed. This study seeks to present a comprehensive analysis of the latest research advancements, the emerging trends in medication therapy, and the utilization of delivery systems in treating DM. The objective is to provide valuable insights into the application of different pharmaceuticals in the field of diabetes mellitus treatment. Also, the therapeutic approach for diabetic patients infected with COVID-19 will be highlighted. Recent clinical and experimental studies evidence the Egyptian experience. Finally, as per the knowledge of the state of the art, our conclusion and future perspective will be declared.

Invasive Seaweed Rugulopteryx okamurae: A Potential Source of Bioactive Compounds with Antioxidant Activity

Rugulopteryx okamurae (RO) is a species of brown seaweed that has invaded several shorelines worldwide, including the Spanish Mediterranean and the Strait of Gibraltar coasts, causing serious environmental and economic problems. This work aimed to characterize the bioactive composition of RO. A high content of carbohydrates (58.7 ± 2.6 wt%), fats (17.1 ± 0.4 wt%), and ashes (14.3 ± 0.2 wt%) were found, together with lower protein content (5.5 ± 1.8 wt%). Holocellulose was the most abundant polysaccharide fraction (49.2 ± 1.3 wt%), showing 43.4 ± 2.0 wt% of cellulose and 5.8 ± 0.7 wt% of hemicellulose, followed by lignin (18.9 ± 2.5 wt%). The monosaccharides composition showed a high level of glucose (13.2 ± 1 wt%) and glucuronic acid (9.3 ± 0.5 wt%). RO contained high levels of essential nutrients (Ca, K, Na, S, Mg), trace minerals (Mn, Mo, Se, and Cu), and some toxic heavy metals (Ni, Cd, As). The main fatty acid present in RO was palmitic acid (C16:0, 30.8 ± 3.0 mg/100 g), followed by myristic acid (C14:0, 19.3 ± 2.4 mg/100 g) and eicosatetraenoic acid (C20:4, 19.2 ± 1.3 mg/100 g). The extract obtained by microwave-assisted extraction (MAE) presented significant contents of polyphenols (2.7 ± 0.2 mg GAE/g) and antioxidant activity (3.0 ± 0.4 mg TE/g DPPH, 4.5 ± 0.3 mg TE/g ABTS, 4.7 ± 0.3 mg TE/g FRAP). Six main polyphenols were identified by HPLC-MS/MS, showing higher contents of gallic acid (20.7 ± 1.5 mg/g) and chlorogenic acid (9.7 ± 0.5 mg/g). These results highlight the possibilities offered in the valorization of RO to obtain bioactive compounds with antioxidant performance in several applications.

Time-restricted feeding mediated modulation of microbiota leads to changes in muscle physiology in Drosophila obesity models.

Recent research has highlighted the essential role of the microbiome in maintaining skeletal muscle physiology. The microbiota influences muscle health by regulating lipid metabolism, protein synthesis, and insulin sensitivity. However, metabolic disturbances such as obesity can lead to dysbiosis, impairing muscle function. Time-restricted feeding (TRF) has been shown to mitigate obesity-related muscle dysfunction, but its effects on restoring healthy microbiomes remain poorly understood. This study utilizes 16S microbiome analysis and bacterial supplementation to investigate the bacterial communities influenced by TRF that may benefit skeletal muscle physiology. In wild-type and obese Drosophila models (axenic models devoid of natural microbial communities), the absence of microbiota influence muscle performance and metabolism differently. Specifically, axenic wild-type Drosophila exhibited reduced muscle performance, higher glucose levels, insulin resistance, ectopic lipid accumulation, and decreased ATP levels. Interestingly, in obese Drosophila (induced by a high-fat diet or predisposed obesity mutant Sk2), the absence of microbiota improved muscle performance, lowered glucose levels, reduced insulin resistance, and increased ATP levels. TRF was found to modulate microbiota composition, notably increasing Acetobacter pasteurianus (AP) and decreasing Staphylococcus aureus (SA) in both obesity models. Supplementation with AP improved muscle performance and reduced glucose and insulin resistance, while SA supplementation had the opposite effect. This study provides novel insights into the complex interactions between TRF, microbiota, and skeletal muscle physiology in different Drosophila models.

Anisotropic Hollow Structure with Chemotaxis Enabling Intratumoral Autonomic Therapy.

Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a-HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4% and 265% respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi-level porosity and temporal-spatial order of a-HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a-HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues.

Anisotropic Hollow Structure with Chemotaxis Enabling Intratumoral Autonomic Therapy

Effective intratumoral drug penetration is pivotal for successful cancer treatment. However, due to the disrupted capillary networks and poor perfusion in solid tumors, there exist challenges to realize autonomous directional drug penetration and controlled drug release within the tumor. Considering the specificity of glucose within tumor tissue, we draw inspiration from nature and engineer asymmetrical hollow structures exhibiting chemotaxis towards high glucose levels. By incorporating multiple shells into these structures, we enhance the local chemical concentration gradients, thereby improving cellular uptake and precise targeting. The advantages of anisotropic hollow multishell structure (a‐HoMS) can be reflected from the diffusion coefficient and directivity, which increase by 73.4% and 265% respectively compared to conventional isotropic hollow spheres, achieving the most linear movement while ensuring the speed of movement. Furthermore, the multi‐level porosity and temporal‐spatial order of a‐HoMS enable sequential drug delivery that inhibits angiogenesis with inducing cell apoptosis. After the eradication of localized tumor cells, the a‐HoMS can automatically migrate to the alive tumor cells under the glucose gradient, inducing another cycle of drug delivery and chemotaxis, resulting in excellent antitumor efficacy. These anisotropic HoMS demonstrate intelligence, adaptability, and precision in tumor therapy, providing valuable insights for programmable treatment within tissues.

Sex differences in the prevalence of metabolic syndrome and associated factors in the general population of Mongolia: A nationwide study.

The prevalence and factors associated with metabolic syndrome (MetS) between men and women in Mongolia were compared using secondary data from the STEPwise approach to non-communicable disease risk factor surveillance conducted in 2019. In total, 5,695 participants (2,577 males and 3,118 females) aged 18-69 years old were enrolled in the study. The prevalence of MetS was 37.4% in total and the prevalence was significantly higher in women (39.2%) than men (35.2%, P = 0.002). The most prevalent MetS components were abdominal obesity in women (74.2%) and high blood glucose levels in men (58.7%). All of the 2,128 participants who were categorized into MetS met the criteria of abdominal obesity. Factors associated with MetS included being 30-69 years old compared to 18-29 years old, low and moderate physical activity levels compared to high levels, history of hypertension and diabetes mellitus, and a high body mass index (overweight and obesity) compared to a normal body mass index in both sexes. Additional factors included Buryat ethnicity compared to Khalkh ethnicity, living in Ulaanbaatar, no education compared to primary education, higher monthly income, and currently drinking in men; and smoking and sufficient fruit and vegetable intake in women. Significant differences were observed between men and women in terms of the prevalence of MetS, components of MetS, and factors associated with MetS. To reduce MetS prevalence in Mongolia, sex-specific programs should be designed to promote health behavior, such as reducing alcohol consumption in men and smoking in women.

Peculiarities of brain cell functioning during hyperglicemia and diabetes mellitus

Hyperglycemia is a symptom and damaging factor of diabetes mellitus (DM) that leads to systemic complications in the body, including macro- and microangiopathies of the brain, impaired blood supply, the appearance of foci of neurodegeneration and might be a trigger of neuroinflammation. Nervous tissue is characterized by a high level of energy consumption and is highly sensitive to fluctuations in the level of metabolic substrates. Therefore, it is extremely important to study the effect of high glucose levels on the functional state of the central nervous system. This review attempts to comprehensively assess the effects of hyperglycemia on brain cells. Analysis of experimental data obtained in in vivo and in vitro models of diabetes on the morphofunctional state of neurons, microglia and astrocytes showed that the direct and indirect effects of glucose in high concentrations depends on the cell type. Receptors and intracellular signaling cascades of astrocytes and microglia, that mediate the effects of hyperglycemia and the development of neuroinflammation, can act as therapeutic targets for the correction for the consequences of diabetes. Thus, finding ways to modulate the functional activity of glial cells may be an effective strategy to reduce the severity of the consequences of CNS damage.

Association between blood glucose level trajectories and 30-day mortality risk in patients with acute ischemic stroke: analysis of the MIMIC database 2001–2019

BackgroundHyperglycemia is one of the most common comorbidities in patients with acute ischemic stroke (AIS). This study aimed to assess the impact of short-term longitudinal blood glucose level change trajectories on the 30-day mortality risk in patients with AIS.MethodsData for AIS patients were obtained from the 2001–2019 Medical Information Mart for Intensive Care (MIMIC) database. The latent growth mixture modeling (LGMM) was utilized to classify a patient’s blood glucose level trajectory within 24 h of admission. Cox regression analyses were applied to examine the relationship between blood glucose levels at admission and blood glucose level trajectories and the risk of 30-day mortality in patients with AIS.ResultsA total of 2,432 patients with AIS were included in this retrospective cohort study, with 30-day mortality occurring in 574 (23.60%) patients. The median glucose levels of all patients were 136.00 (110.00, 178.00) mg/dL. Four blood glucose level trajectories were identified: low level-stable trend (type 1), moderate level-stable trend (type 2), high level-decreasing-increasing trend (type 3), and moderate level-increasing-decreasing trend (type 4). Type 2 blood glucose level trajectory was associated with an increased risk of 30-day mortality compared with type 1 blood glucose level trajectory [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 1.03–1.59), but there were no significant associations between type 3 (HR = 1.16, 95%CI: 0.77–1.74) and type 4 (HR = 1.44, 95%CI: 0.84–2.45) trajectories and 30-day mortality risk. Subgroup analysis demonstrated that the association between type 2 trajectory and 30-day mortality risk was observed in patients aged ≥ 65 years (HR = 1.37, 95%CI: 1.05–1.79), female (HR = 1.42, 95%CI: 1.05–1.94), with (HR = 1.44, 95%CI: 1.02–2.02) or without (HR = 1.42, 95%CI: 1.01–1.99) diabetes, and not using insulin (HR = 2.80, 95%CI: 1.43–5.49).ConclusionAIS patients with consistently high blood glucose levels within 24 h of admission increased the risk of 30-day mortality.

High glucose condition aggravates inflammatory response induced by Porphyromonas gingivalis in THP-1 macrophages via autophagy inhibition

BackgroundPorphyromonase gingivalis (P. gingivalis) is a type of bacteria that causes periodontitis, which is strongly correlated with systemic diseases such as diabetes. However, the effect of hyperglycemia on periodontitis are unclear. The present study examined the effects of high glucose levels on the response to P. gingivalis infection.ResultsThe expression of P. gingivalis-induced interleukin-1β (IL-1β) and inflammasomes increased as the glucose concentration increased. High glucose conditions suppressed P. gingivalis–induced autophagy in human acute monocytic leukemia cell line (THP-1) macrophages. Zingerone increased autophagy and alleviated P. gingivalis-induced inflammatory response in THP-1 macrophages under high glucose conditions. In addition, P. gingivalis- induced inflammation in bone marrow-derived macrophages of diabetic mice was higher than in wild-type mice, but a zingerone treatment decreased the levels. Alveolar bone loss due to a P. gingivalis infection was significantly higher in diabetic mice than in wild-type mice.ConclusionsHigh-glucose conditions aggravated the inflammatory response to P. gingivalis infection by suppressing of autophagy, suggesting that autophagy induction could potentially to treat periodontitis in diabetes. Zingerone has potential use as a treatment for periodontal inflammation induced by P. gingivalis in diabetes patients.

Identification of Candida albicans in the Urine of Type 2 Diabetes Mellitus Patiens at Puskesmas Jaten 2, Karanganyar Regency

Background: Candida albicans is an opportunistic fungus that thrives in environments with high glucose concentrations, which makes patients with Diabetes Mellitus (DM) especially vulnerable to infection. Elevated blood glucose levels in DM can lead to glycosuria, providing a rich nutrient source for fungal growth. This research is critical because there is a lack of specific studies focusing on fungal infections in diabetic patients in Indonesia, despite the increasing prevalence of DM. This research provides a new perspective by highlighting a local diabetic population that has not been extensively studied before. Objective: The objective of this study is to identify the presence of Candida albicans in the urine of Type 2 Diabetes Mellitus patients at Puskesmas Jaten 2 in Karanganyar Regency. Materials and Methods: This descriptive study included 20 urine samples from Type 2 Diabetes Mellitus patients. The inclusion criteria were fasting blood glucose levels of 200 mg/dl or higher, and all patients were enrolled in the chronic disease management program (Prolanis) at Puskesmas Jaten 2. The samples were collected and examined macroscopically in February 2024 to detect the presence of Candida albicans. Results: The results showed that Candida albicans was found in 6 out of 20 urine samples (30%), while the fungus was not detected in 14 samples (70%). The majority of positive cases occurred in patients aged 50 and older, suggesting an age-related susceptibility to fungal infection in this population. Patients with higher glucose levels also showed a greater tendency for Candida growth. Conclusions: Based on the results of this study, it can be concluded that Candida albicans is present in the urine of Type 2 Diabetes Mellitus patients at Puskesmas Jaten 2, with a notable prevalence of 30%. This finding highlights an increased susceptibility to fungal infections in older patients and those with elevated glucose levels, suggesting the need for careful monitoring and potential intervention in this population. Further studies with larger sample sizes are suggested to confirm these results and explore additional preventive measures.

Smart photonic crystal hydrogels for visual glucose monitoring in diabetic wound healing

Diabetes is a global chronic disease that seriously endangers human health and characterized by abnormally high blood glucose levels in the body. Diabetic wounds are common complications which associate with impaired healing process. Biomarkers monitoring of diabetic wounds is of great importance in the diabetes management. However, actual monitoring of biomarkers still largely relies on the complex process and additional sophisticated analytical instruments. In this work, we prepared hydrogels composed of different modules, which were designed to monitor different physiological indicators in diabetic wounds, including glucose levels, pH, and temperature. Glucose monitoring was achieved based on the combination of photonic crystal (PC) structure and glucose-responsive hydrogels. The obtained photonic crystal hydrogels (PCHs) allowed visual monitoring of glucose levels in physiological ranges by readout of intuitive structural color changes of PCHs during glucose-induced swelling and shrinkage. Interestingly, the glucose response of double network PCHs was completed in 15 min, which was twice as fast as single network PCHs, due to the higher volume fraction of glucose-responsive motifs. Moreover, pH sensing was achieved by incorporation of acid-base indicator dyes into hydrogels; and temperature monitoring was obtained by integration of thermochromic powders in hydrogels. These hydrogel modules effectively monitored the physiological levels and dynamic changes of three physiological biomarkers, both in vitro and in vivo during diabetic wound healing process. The multifunctional hydrogels with visual monitoring of biomarkers have great potential in wound-related monitoring and treatment.Graphical abstract

Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors in Diabetic Retinopathy: An Attractive but Elusive Choice for Drug Development.

Owing to its promiscuous roles, poly (ADP-ribose) polymerase-1 (PARP-1) is involved in various neurological disorders including several retinal pathologies. Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus affecting the retina. In the present review, we highlight the importance of PARP-1 participation in pathophysiology of DR and discuss promising potential inhibitors for treatment. A high glucose level enhances PARP-1 expression; PARP inhibitors have gained attention due to their potential therapeutic effects in DR. They target different checkpoints (blocking nuclear transcription factor (NF-κB) activation; oxidative stress protection, influence on vascular endothelial growth factor (VEGF) expression, impacting neovascularization). Nowadays, there are several improved clinical PARP-1 inhibitors with different allosteric effects. Combining PARP-1 inhibitors with other compounds is another promising option in DR treatments. Besides pharmacological inhibition, genetic disruption of the PARP-1 gene is another approach in PARP-1-initiated therapies. In terms of future treatments, the limitations of single-target approaches shift the focus onto combined therapies. We emphasize the importance of multi-targeted therapies, which could be effective not only in DR, but also in other ischemic conditions.

Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study

To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, patients were administered oral anlotinib (12 mg/day) on days 1–14 and intravenous sintilimab (200 mg) on day 1 of a 3-weekly cycle. The primary endpoints included the objective response rate and disease control rate. The secondary endpoints included overall survival (OS) and safety. Ten eligible patients were enrolled between June 2019 and May 2022, and eight patients underwent radiographic assessments. The results showed an objective response rate of 50% (partial and complete response in four and zero patients, respectively) and a disease control rate of 100%; four patients demonstrated stable disease for at least 8 weeks. The median OS was 4.37 (in our study, the score was 7), and the OS rate at 12 months was 37.5%. The Kaplan–Meier survival curve showed that the group with high blood glucose levels had a significantly shorter duration of survival than those with normal blood glucose levels. Adverse events of grade 3 and higher occurred in 50% of patients, and the most common severe adverse events included tumor pain (50%), hypertension (37.5%), tumor hemorrhage (25%), and decreased appetite (25%). The combination of anlotinib and sintilimab showed promising efficacy in controlling tumor size. However, the disappointing OS rate suggests that anti-vascular endothelial growth factor receptor agents should be used cautiously after radical radiation therapy. The combination used in this study demonstrated a toxicity profile comparable to that of other agents used in this setting. These findings warrant further investigation into the potential clinical utility of this combination.

Can simple biomarkers of inflammation guide the diagnosis of psychiatric disorders?

Objective In this study, we wanted to investigate the usability of routine blood samples taken at the beginning of hospitalisation in inpatients to predict the presence of psychotic symptoms in patients. Methods We divided the hospitalised patients into two groups those with and without psychotic symptoms according to their ICD-10 diagnosis codes. Then, we compared the complete blood count, c-reactive protein (CRP), and fasting glucose levels, which can be used as simple markers of inflammation. Results In this retrospective study, which included 349 patients, we found that blood leukocytes, neutrophils, CRP, and fasting glucose levels were higher in patients with psychotic symptoms than in patients without psychotic symptoms (p = 0.015; p = 0.013; p = 0.002; and p = 0.001, respectively). According to regression analysis, patients with high glucose levels were 4.9 times more likely to have psychotic symptoms than those with low glucose levels. In addition, according to the ROC analysis results; when we used 87 mg/dl as the cut-off value for fasting glucose, it was observed that it predicted psychotic symptoms with approximately 69% sensitivity and 71% specificity. Conclusion Although our results still have some limitations, they are promising for the future use of simple biomarkers of inflammation for the differential diagnosis of psychiatric disorders.