A Systematic Review of Semaglutide's Influence on Cognitive Function in Preclinical Animal Models and Cell-Line Studies.

Since we aim to test new options to find medication for cognitive disorders, we have begun to assess the effect of semaglutide and to conduct a review gathering studies that have attempted this purpose. This systematic review focuses on the cognitive effects of semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), in the context of neurological and cognitive impairment. Semaglutide, a synthetic GLP-1 analog, showcased neuroprotective effects beyond metabolic regulation. It mitigated apoptosis and improved cognitive dysfunction in cerebrovascular disease, suggesting broader implications for neurological well-being. Also, studies highlighted GLP-1 RAs' positive impact on olfactory function in obese individuals with type 2 diabetes, on neurodegenerative disorders, multiple sclerosis, and endotoxemia. In order to analyze current studies that assess the impact of semaglutide on cognitive function, a literature search was conducted up to February 2024 on two online databases, MEDLINE (via PubMed) and Web of Science Core Collection, as well as various websites. Fifteen studies on mice populations and two studies on cell lines were included, analyzed, and assessed with bias-specific tools. The neuroprotective and anti-apoptotic properties of GLP-1 and its analogs were emphasized, with animal models and cell line studies demonstrating enhanced cognitive function. While promising, limitations include fewer studies, highlighting the need for extensive research, particularly in the human population. Even though this medication seems promising, there are significant limitations, one of which is the lack of studies on human subjects. Therefore, this review aims to gather current evidence.

PI3K/AKT/mTOR Dysregulation and Reprogramming Metabolic Pathways in Renal Cancer: Crosstalk with the VHL/HIF Axis.

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.

Incidence of Lower Extremity Amputation in Romania: A Nationwide 5-Year Cohort Study, 2015-2019.

Background and Objectives: The primary objective of this study was to investigate the incidence of lower extremity amputations (LEAs) in a representative population from Romania, in both diabetic and non-diabetic adults, including trauma-related amputations. The secondary objective was to evaluate the trends in LEAs and the overall ratio of major-to-minor amputations. Material and Methods: The study was retrospective and included data from the Romanian National Hospital Discharge Records, conducted between 1 January 2015 and 31 December 2019. Results: The overall number of cases with LEAs was 88,102, out of which 38,590 were aterosclerosis-related LEAs, 40,499 were diabetes-related LEAs, and 9013 were trauma-related LEAs, with an ascending trend observed annually for each of these categories. Of the total non-traumatic amputations, 51.2% were in patients with diabetes. Most LEAs were in men. The total incidence increased from 80.61/100,000 in 2015 to 98.15/100,000 in 2019. Conclusions: Our study reported a 21% increase in total LEAs, 22.01% in non-traumatic LEAs, and 19.65% in trauma-related amputation. The minor-to-major amputation ratio increased over the study period in patients with diabetes. According to these findings, it is estimated that currently, in Romania, there is one diabetes-related amputation every hour and one non-traumatic amputation every 30 min.

Exosome Proteomics Reveals the Deregulation of Coagulation, Complement and Lipid Metabolism Proteins in Gestational Diabetes Mellitus.

Exosomes are small extracellular vesicles with a variable protein cargo in consonance with cell origin and pathophysiological conditions. Gestational diabetes mellitus (GDM) is characterized by different levels of chronic low-grade inflammation and vascular dysfunction; however, there are few data characterizing the serum exosomal protein cargo of GDM patients and associated signaling pathways. Eighteen pregnant women were enrolled in the study: 8 controls (CG) and 10 patients with GDM. Blood samples were collected from patients, for exosomes' concentration. Protein abundance alterations were demonstrated by relative mass spectrometric analysis and their association with clinical parameters in GDM patients was performed using Pearson's correlation analysis. The proteomics analysis revealed 78 significantly altered proteins when comparing GDM to CG, related to complement and coagulation cascades, platelet activation, prothrombotic factors and cholesterol metabolism. Down-regulation of Complement C3 (C3), Complement C5 (C5), C4-B (C4B), C4b-binding protein beta chain (C4BPB) and C4b-binding protein alpha chain (C4BPA), and up-regulation of C7, C9 and F12 were found in GDM. Our data indicated significant correlations between factors involved in the pathogenesis of GDM and clinical parameters that may improve the understanding of GDM pathophysiology. Data are available via ProteomeXchange with identifier PXD035673.

Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP.

Sunlight is the most abundant energy source on this planet. However, the ability to convert sunlight into biological energy in the form of adenosine-5'-triphosphate (ATP) is thought to be limited to chlorophyll-containing chloroplasts in photosynthetic organisms. Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll. The same metabolite fed to the worm Caenorhabditis elegans leads to increase in ATP synthesis upon light exposure, along with an increase in life span. We further demonstrate the same potential to convert light into energy exists in mammals, as chlorophyll metabolites accumulate in mice, rats and swine when fed a chlorophyll-rich diet. Results suggest chlorophyll type molecules modulate mitochondrial ATP by catalyzing the reduction of coenzyme Q, a slow step in mitochondrial ATP synthesis. We propose that through consumption of plant chlorophyll pigments, animals, too, are able to derive energy directly from sunlight.

Benzophenone and its analogs bind to human glyoxalase 1.

Benzophenone is a popular photophore for photoaffinity-labeling. It is also an important framework for drug development; many drugs contain benzophenone or analogous frameworks. The current work reports that benzophenone and its analogs bind to human glyoxalase 1. The binding, however, has little effect on the catalytic activity of this enzyme. The implications of the finding in terms of both drug development and photoaffinity-labeling are discussed.

The photosynthetic eukaryote Nannochloris eukaryotum as an intracellular machine to control and expand functionality of human cells.

To construct an intracellular machine, we sought a symbiotic relationship between a photosynthetic green alga and human cells. Human cells selectively take up the minimal eukaryote Nannochloris eukaryotum and the resulting symbionts are able to survive and proliferate. Host cells can utilize N. eukaryotum's photosynthetic apparatus for survival, and expression of cellular vascular endothelial growth factor can be controlled with input of photonic energy. This seemingly rare spontaneous association provides an opportunity to fabricate light-controlled, intracellular machines.

Diabetes Distress Among the Roma Population From a Tertiary Care Center in Romania.

Background Distress in patients with diabetes is a condition that has received significant attention in recent years; however, data regarding the psychological assessment and the impact of the emotional burden of diabetes among the Roma population are still scarce in the medical literature. Material and methods We conducted an observational, transversal study that included 310 adult patients with diabetes mellitus, aged between 18 and 85 years old, of which the majority (61%) were women; patients were selected from a tertiary hospital providing diabetes care; diabetes distress was evaluated using a standardized questionnaire, the diabetes distress scale (DDS), validated on Romanian patients. Results In the study population, a great proportion of patients showed diabetes distress, with 24.8% (N=82) having moderate distress and 29.7% (N=121) having severe distress. In the Caucasian group, there were significantly more patients without distress than in the Roma patients,while on the contrary, more Roma patients experienced severe distress compared to the opposite group (64.5%, N=78 versus 35.5%, N=43). In the Caucasian group, a statistical significance was observed regarding interpersonal distress, with Caucasian women having a higher score than men. Concerning the Roma patients, total DDS and all subscales´ scores were statistically significant, with Roma women having higher scores than men. A statistical significance was observed between ethnicity and diabetes distress scores, with the Roma population having higher median values than Caucasian patients. It was also demonstrated that the lack of education, a higher diabetes evolution, and a higher glycated hemoglobin (HbA1c) level (above 8%) have influenced the risk of severe DDS in the Caucasian group, while in the Roma patients, employment status (being unemployed) represents a risk factor for severe DDS. Conclusion The Roma patients included in our study experienced higher distress scores compared to Caucasians. These results are substantial as they emphasize the need to include the evaluation of diabetes distress in clinical practice to facilitate the early initiation of intervention measures. There is nevertheless limited data regarding this particular ethnic group; therefore, further research is still needed.

The retina rapidly incorporates ingested C20-D3-vitamin A in a swine model.

PURPOSE: To determine how the retina uses vitamin A for vision, we studied the flux of oral vitamin A into and out of the swine retina. METHODS: We administered labeled vitamin A to swine daily for 30 days and measured the percent of the labeled vitamin A to native unlabeled vitamin A in the retinal epithelium, neuroretina, plasma, liver, lung, and kidney. RESULTS: We show that during normal vitamin A homeostasis, the retina rapidly assimilates newly ingested dietary vitamin A, which replaces native vitamin A. Retinal vitamin A is turned over faster than previously thought. Provitamin A carotenoids do not significantly contribute to retinal vitamin A pools when consuming diets adequate in vitamin A. CONCLUSIONS: Fast vitamin A turnover in the retina has direct implications for emerging therapies to prevent major forms of blindness based on controlling the concentrations of retinal vitamin A.

Changes in C-Peptide Values in Children with Type 1 Diabetes - a Three-Year Study.

Background: C-peptide is used as an important indicator of residual insulin secretion in patients diagnosed with type 1 diabetes mellitus (T1DM) and treated with insulin. Aim:We have aimed to monitor the serum C-peptide (CP) levels during the first three years after diagnosis of T1DM in a cohort of children admitted to the Diabetes Department of "M. S. Curie" Emergency Clinical Hospital for Children, Bucharest, Romania, and to investigate the factors that could influence the rate of decline in its secretion. Method:We conducted a longitudinal, retrospective cohort study on a group of 215 children and adolescents who met the inclusion criteria and were monitored in our clinic over the course of a long period of time. We analyzed several parameters, including fasting serum CP values at diagnosis and yearly throughout T1DM evolution, the severity of diabetic ketoacidosis (DKA) at onset, HbA1c at diagnosis, family history of T1DM/T2DM, patient gender and presence of concurrent acute infectious disease at diagnosis, with the purpose of evaluating their influence on the preservation of endogenous insulin secretion. Based on serum CP value measured three years after T1DM onset, patients were divided into two groups: group 1, with low insulin residual secretion (CP < 0.6 ng/mL), and group 2, with preserved insulin residual secretion (CP ≥0.6 ng/mL) Results:At the moment of diagnosis, patients in group 1 were younger than those in group 2 (6.03 ± 3.54 years and 9.76 ± 2.75 years, respectively). The proportion of children with diabetic ketoacidosis (DKA) at onset was greater in group 1 (68% of patients) than group 2, in which the majority of subjects (60%) did not have DKA. The C-peptide value at diagnosis was significantly lower (0.55 ± 0.36 ng/mL) among patients in group 1 than those in group 2 (1.11 ± 0.59 ng/mL). In group 1 there was a higher proportion of patients (65%) with acute infectious disease at onset. Family history of T1DM/T2DM was associated with a more rapid decline in CP values. Our data showed no correlation between CP levels monitored for three years and HbA1c at diagnosis and no association with the gender of each patient. Conclusion:Patients with higher CP concentrations at diagnosis maintained increased values (> 0.6 ng/mL) three years after disease onset. Younger children had a faster decline of CP secretion during the first three years following diabetes diagnosis. In patients with severe symptoms (DKA) and associated infectious disease at onset, a risk of rapid CP decline was found.

The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus.

AIM: We evaluated the safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for their use with other glucose-lowering drugs and drugs for the treatment of type 2 diabetes mellitus (T2DM), in a standard-of-care regimen with maximum tolerated doses, and, respectively, when compared with metformin. METHODS: We conducted a retrospective, observational study on 405 patients that were seen in the outpatient clinic of the N Paulescu National Institute for Diabetes Mellitus, Bucharest, Romania, in 2019. Their demographics, metabolic parameters, and medication safety were evaluated at three follow-up visits, from baseline, six months, and twelve months. RESULTS: Both SGLT-2is and GLP-1 RAs are safe regarding creatinine, eGFR, urea, GOT, and GPT upon the comparison of the data from the six- and twelve-month visits with the initial visit, and also the twelve-month visit with the six-month visit. Moreover, when comparing SGLT-2is and GLP-1 RAs with metformin, there are safety data only for urea. CONCLUSIONS: In this retrospective analysis, both SGLT-2is and GLP-1 RAs, when used in conjunction with other glucose-lowering, blood-pressure-lowering, and lipid-lowering medications, appeared to be safe for the management of T2DM.

New born macrosomia in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic complication of pregnancy. The pathogenesis of GDM is considered to involve ß-cell dysfunction and insulin resistance (IR). GDM is associated with a significant risk of macrosomia in addition to a high probability of metabolic complications for the offspring. The precise mechanism underlying GDM remains unclear. The aim of the present study was to analyse the factors associated with insulin resistance and ß-cell dysfunction involved in the pathophysiology of GDM complicated with macrosomia compared with GDM without macrosomia. In addition, another aim of the present study was to assess the relationship between GDM complicated with macrosomia and anthropometric, clinical and paraclinical parameters. The following group of patients were recruited as part of a case-control study: Patients with GDM without macrosomia, patients with GDM complicated with macrosomia and healthy gestational controls. Blood samples were collected at the third trimester of pregnancy and tested for adiponectin, leptin, insulin, proinsulin and C-peptide. Homeostatic model assessment-IR (HOMA-IR), steady state ß-cell function (HOMA%B), insulin sensitivity (HOMA%S) and body mass index (BMI) were also calculated. All patients diagnosed with GDM showed an impairment in HOMA%B and a decrease in C-peptide maternal serum concentration. Additionally, diabetic status leading to the birth of offspring with macrosomia did not induce changes in the maternal serum levels of insulin, proinsulin, adiponectin or leptin, which was also the case in patients with GDM but not macrosomia. HOMA%B presented a stronger positive correlation with pre-pregnancy BMI and maternal weight gain, and a stronger negative correlation with adiponectin. Furthermore, HOMA%S in this group exhibited strong positive correlations with maternal serum levels of high-density lipoprotein cholesterol (HDL) and aspartate aminotransferase, and a strong negative correlation with pre-pregnancy BMI. In the same patients, HOMA-IR was also found to have a high negative correlation with HDL levels, and highly positive correlations with gestational age and triglyceride levels. In conclusion, the present study suggests that the different correlations among the factors involved in the pathogenesis of GDM may explain the evolution of GDM pregnancy to macrosomia.

Continuous glucose monitoring devices: A brief presentation (Review).

As diabetes prevalence is continuously increasing, better management is needed to achieve blood glucose control, in order to prevent complications and lessen the burden of this disease. Since the first measurement of glycosuria at the beginning of the 1900s', huge advances were made in monitoring glycemia. Continuous glucose monitoring systems revolutionized diabetes management, especially for patients with type 1 diabetes. Avoiding glycemic variability and maintaining optimal glycemic control is crucial for the evolution of patients with type 1 diabetes. The usefulness of glycemic monitoring devices can be extended to patients with type 2 diabetes. It is also important to note that in those patients at risk of developing high glycemic variability (e.g. patients with advanced chronic kidney disease), continuous glycemic monitoring may improve their prognosis. These monitoring systems can be classified according to the analytical method, the degree of invasiveness, the data availability and the mode of usage. The technology is constantly improving in bioanalytical performance, biocompatibility, length of wearing time, safety and clinical features. The aim of this review was to briefly present the main characteristics of glucose biosensors, glucose monitoring systems and their clinically utility.

Non-Insulin Novel Antidiabetic Drugs Mechanisms in the Pathogenesis of COVID-19.

The present study aimed to analyse the published data and to realize an update about the use and pathogenesis of the novel antidiabetic drugs, respectively, dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 Ra), and sodium-glucose co-transporter-2 inhibitors (SGLT-2i), in patients with type 2 diabetes mellitus (T2DM) and coronavirus disease (COVID-19). Literature research in the PubMed and Web of Science database was performed in order to identify relevant published clinical trials and meta-analyses that include information about the treatment with novel antidiabetic agents in patients with T2DM and COVID-19. A total of seven articles were included, and their primary and secondary outcomes were reported and analysed. DPP-4i has mixed results on mortality in T2DM patients with COVID-19 but with an overall slightly favourable or neutral effect, whereas GLP-1 Ra seems to have a rather beneficial impact, while SGLT-2i may be useful in acute illness. Even if there are limited data, they seem to have favourable efficacy and safety profiles. The available evidence is heterogenous and insufficient to evaluate if the benefits of non-insulin novel antidiabetic drugs in COVID-19 treatment are due to the improvement of glycaemic control or to their intrinsic anti-inflammatory effects but highlights their beneficial effects in the pathogenesis and evolution of the disease.

Reproducible enrichment of extracellular heat shock proteins from blood serum using monomeric avidin.

Extracellular heat shock proteins (eHsps) in blood circulation have been associated with various diseases, including cancer. However, the lack of methods to enrich eHsps from serum samples has hampered the characterization of eHsps. This Letter presents our serendipitous finding that the monomeric avidin resin can serve as an affinity resin to enrich eHsps from blood serum. Biochemical mechanism of this eHsp enrichment as well as implications in biomarker discovery is discussed.

Vitamin A cycle byproducts explain retinal damage and molecular changes thought to initiate retinal degeneration.

In the most prevalent retinal diseases, including Stargardt disease and age-related macular degeneration (AMD), byproducts of vitamin A form in the retina abnormally during the vitamin A cycle. Despite evidence of their toxicity, whether these vitamin A cycle byproducts contribute to retinal disease, are symptoms, beneficial, or benign has been debated. We delivered a representative vitamin A byproduct, A2E, to the rat's retina and monitored electrophysiological, histological, proteomic, and transcriptomic changes. We show that the vitamin A cycle byproduct is sufficient alone to damage the RPE, photoreceptor inner and outer segments, and the outer plexiform layer, cause the formation of sub-retinal debris, alter transcription and protein synthesis, and diminish retinal function. The presented data are consistent with the theory that the formation of vitamin A byproducts during the vitamin A cycle is neither benign nor beneficial but may be sufficient alone to cause the most prevalent forms of retinal disease. Retarding the formation of vitamin A byproducts could potentially address the root cause of several retinal diseases to eliminate the threat of irreversible blindness for millions of people.

Hypocalcemia: A possible risk factor for anastomotic leak in digestive surgery.

Anastomotic leaks (ALs) remain the most severe complication in digestive surgery, as well as the most consumptive in terms of human and financial resources. There is an abundance of international research which has focused on identifying and correcting risk factors, and on individualized surgical management as well. The most frequent risk factors are male sex, obesity, diabetes, advanced malignant disease, ASA score, perioperative blood loss or perioperative transfusion, long operation time, emergency operation and altered nutritional status. The aim of the present study was to measure the preoperative serum calcium level and to find a possible correlation between calcium levels and the risk of AL occurrence. A retrospective analysis of medical records for 122 patients who underwent surgical gut resection with anastomosis for different pathologies was carried out. Preoperative serum calcium level and the occurrence of AL was noted. The results revealed that the average value of total blood calcium was 8.78 mg/dl, without a significant difference in sex groups. Hypocalcemia was identified in 44 patients (36.1%). AL was identified in 8 patients (6.6%), with a statistically insignificant difference between male and female patients. The average value of blood calcium in the AL patient group was 8.07 mg/dl, while in patients without AL the average value was 8.83 mg/dl. Hypocalcemia, defined as a serum calcium level below 8.5 mg/dl, was observed in 7 of the 8 patients presenting with AL (87.5%) and 37 patients who did not present with AL (32.5%), a significant difference with which to consider and include hypocalcemia in the group of risk factors for AL (P=0.001). In conclusion, preoperative low serum calcium level can represent a risk factor for AL in digestive surgery.

Impact of adipose tissue in chronic kidney disease development (Review).

Obesity is a worldwide pandemic health issue. Obesity is associated with the pathogenesis of type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, cancer, and kidney diseases. This systemic disease can affect the kidneys by two mechanisms: Indirectly through diabetes mellitus (DM) and hypertension and directly through adipokines secreted by adipose tissue. Obesity is a risk factor for chronic kidney disease (CKD), which is associated with an increased risk of morbidity and mortality among the adult population. Increased visceral adipose tissue leads to renal glomerular hyperfiltration and hyperperfusion, which may lead to glomerular hypertrophy, proteinuria, and CKD development. Adipokines are hormones produced by fat tissue. They are involved in energy homeostasis, sugar and fat metabolism, reproduction, immunity, and thermogenesis control. Hormones and cytokines secreted by adipose tissue contribute to the development and progression of CKD. Decreased serum or urinary adiponectin levels are specific in diabetic and non-diabetic CKD patients, while leptin presents increased levels, and both are associated with the development of glomerulopathy. Excessive adipose tissue is associated with inflammation, oxidative stress (OS), insulin resistance and activation of the renin angiotensin-aldosterone system (RAAS). Therefore, adipose tissue dysfunction plays an important role in the development of CKD.

PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).

Renal cell carcinoma (RCC) accounts for over 90% of all renal malignancies, and mainly affects the male population. Obesity and smoking are involved in the pathogenesis of several systemic cancers including RCC. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway regulates cell growth, differentiation, migration, survival, angiogenesis, and metabolism. Growth factors, hormones, cytokine and many extracellular cues activate PI3K/AKT/mTOR. Dysregulation of this molecular pathway is frequently reported in human cancers including RCC and is associated with aggressive development and poor survival rate. mTOR is the master regulator of cell metabolism and growth, and is activated in many pathological processes such as tumour formation, insulin resistance and angiogenesis. mTOR inhibitors are used at present as drug therapy for RCC to inhibit cell proliferation, growth, survival, and the cell cycle. Temsirolimus and everolimus are two mTOR inhibitors that are currently used for the treatment of RCC. Drugs targeting the PI3K/AKT/mTOR signalling pathway may be one of the best therapeutic options for RCC.

The effects of some Curdlan derivatives on Dectin-1 expression and cytokine production in human peripheral blood mononuclear cells.

The cells of immune system such as monocytes and macrophages are in first line defence against dangerous signals. In the present paper the recognition of Dectin 1 receptors and the modulation of Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-alpha) cytokine production by Curdlan and Curdlan derivatives in peripheral blood mononuclear cells (PBMCs) were studied. The effect of Curdlan or Curdlan derivatives on the expression of Dectin 1 receptors in PBMCs was revealed by flow-cytometry and the levels of IL-10 and TNFalpha were measured by ELISA kit in supernatants of PBMCs cultured in presence or absence of Curdlan, Curdlan derivatives and LPS. Our results suggested that Curdlan and Curdlan derivatives were able to increase the expression of Dectin-1 receptors on monocyte cells. The combined treatment of Curdlan/Curdlan derivatives and Pam3Cys produced an increase of CD14+ cells possessing Dectin-1 receptors. We demonstrated that Curdlan (at 20 microg unique dose) up-regulated TNF-alpha production and down-regulated IL-10 production in PBMCs. Conversely, Palm CM/SP-Curdlan (20 microg unique dose) was able to down-regulate TNF-alpha production and to up-regulate IL-10 production in PBMCs. For instance, Palm CM/SP-Curdlan determined a 5 times decrease of TNF-alpha production than Curdlan. Regarding the effect of Palm CM/SP-Curdlan on IL-10 production in PBMCs, we noticed that the level of IL-10 was about 4 times greater than Curdlan activity. We observed that a combined treatment of Curdlan/Curdlan derivatives and LPS induced about 5 times decrease in TNF-alpha production in PBMCs. IL-10 production induced by Palm CM/SP-Curdlan and LPS was about 6 times greater than the combined effect of Curdlan and LPS. The treatment of PBMCs with SP-Curdlan alone affected neither TNF-alpha production nor IL-10 production. Our results are in accordance with other studies demonstrating that Dectin-1 and TLR2/TLR6 signaling combine to enhance the responses triggered by each receptor and the signaling pathway induced by Dectin-1 could mediate the production of pro-inflammatory cytokines.