Serum Levels Of Protein Research Articles

Erratum in: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.

Erratum in: Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.

Toxicity assessment of a phytomedicine based on an almond extract from the fruit of Balanites aegyptiaca (L.) DELILE (Zygophyllaceae) intended for helminthiases care in Burkina Faso

Balanites aegyptiaca (L.) Delile (Zygophyllaceae) is a medicinal plant used in traditional medicine in Burkina Faso to treat helminthiasis. Using an ethnopharmacological approach, the "Institut de Recherche en Sciences de la Santé (IRSS)" has developed a phytomedicine based on an almond extract from the fruit of this plant for the treatment of helminthiasis. This study aimed to assess the acute and subacute oral toxicity and in vivo mutagenicity of phytomedicine. The acute toxicity study was carried out following OECD guideline 423 by administering a single dose of 2000 mg/kg body weight (bw) of phytomedicine orally to female mice. For subacute toxicity, OECD guideline 407 was used. Four batches of 10 rats (5 males and 5 females) were used, including a control batch and three treated batches receiving a daily oral administration of the phytomedicine at doses of 250, 500, or 1000 mg/kg bw for 28 days. The mutagenicity test was performed according to OECD guideline 474; five batches of 10 mice (5 males and 5 females) were given oral doses of 500, 1000 or 2000 mg/kg bw of phytomedicine, colchicine as a positive control at 5mg/kg bw and distilled water as a negative control. In the acute toxicity test, the LD50 was estimated at 5000 mg/kg bw. The subacute toxicity study showed no mortality or signs of toxicity in rats. Biochemical analysis revealed no significant differences between control rats and those treated with the phytomedicine for glucose, creatinine, total cholesterol, triglycerides, AST, chlorine, calcium, and potassium. On the other hand, serum levels of ALT, total protein, PO43-, and Na+ were significantly reduced in some treated rats. The mutagenicity test showed no change in micronucleus frequency between treated and control mice. This study showed that phytomedicine based on an extract of B. aegyptiaca fines would present less danger to users. Keywords: Balanites aegyptiaca, acute toxicity, subacute toxicity, micronucleated erythrocytes, phytomedicine.

The Mechanism of Baicalin in the Treatment of Mycoplasma Pneumoniae Pneumonia by Regulating NLRP3/Caspase-1 Signaling Pathway

ABSTRACT Objective This study investigated the mechanism of baicalin (BIA) attenuating the inflammatory response and lung injury in mycoplasma pneumoniae pneumonia (MPP) mice. Methods MPP mouse models were established and then treated with BIA, azithromycin, or NLRP3 inflammasome activator. Lung wet-to-dry weight (W/D) ratio were weighed. Serum levels of MP-IgM, C-reactive protein (CRP) and bronchoalveolar lavage fluid (BALF) protein were detected by kits, NLRP3/Caspase-1 pathway-related protein levels by Western blot, and IL-1β, IL-18, IL-6 and TNF-α levels by ELISA. HE staining was performed to detect lung injury. Results MPP mice showed elevated mouse lung W/D ratio, upregulated serum MP-IgM and CRP levels and BALF protein, and enhanced IL-6 and TNF-α levels, which were reversed by BIA or azithromycin treatment, suggesting that BIA attenuated pulmonary inflammatory response in MPP mice. The lung tissue of MPP mice showed upregulated NLRP3, cleaved Caspase-1,Caspase-1, GSDMD-N and GSDMD levels and raised IL-1β and IL-18 levels, and changes were annulled by BIA or azithromycin treatment, suggesting that BIA inhibited the NLRP3/Caspase-1 pathway activation. NLRP3/Caspase-1 pathway activation partially abrogated the alleviative effect of BIA on the pulmonary inflammatory response of MPP mice. Conclusion BIA mitigates inflammatory response and lung injury in MPP mice by inhibiting NLRP3/Caspase-1 pathway activation.

Comparison of midazolam and dexmedetomidine combined with thoracic paravertebral block in hemodynamics, inflammation and stress response, and cognitive function in elderly lung cancer patients.

This study aimed to compare the clinical outcomes of midazolam and dexmedetomidine combined with ropivacaine-induced thoracic paravertebral nerve block (TPVB) in radical lung cancer surgery. To retrospectively analyze the clinical data of elderly patients who underwent thoracoscopic radical lung cancer surgery from March 2020 to February 2023 in our hospital. All patients underwent a single two-site method of TPVB at the levels of T4 and T7 under ultrasound guidance. The patients were divided into midazolam group (0.25% ropivacaine+0.1mg/kg midazolam) and dexmedetomidine group (0.25% ropivacaine+0.8μg/kg dexmedetomidine) according to the application of sedative drugs, with 78 cases in each group. Ramsay sedation score, mean arterial pressure (MAP), heart rate (HR), electroencephalographic bispectral index (BIS), and blood oxygen saturation (SpO2), as well as the serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), epinephrine (E), cortisol (Cor), and norepinephrine (NE) were recorded at 6, 12, 24, 36 and 48h postoperatively, respectively. The patients' cognitive function was assessed using the Brief Mental State Evaluation Scale (MMSE) at 1 d preoperatively, 1 d postoperatively, and 7 d postoperatively. The amount of intraoperative sufentanil in the dexmedetomidine group was lower than that in the midazolam group (P<0.05). The rate of atropine use was higher in the dexmedetomidine group than that in the midazolam group (P<0.05). There was no significant difference in the occurrence of overall intraoperative adverse reactions (P>0.05), but the incidence of respiratory depression in the dexmedetomidine group was significantly lower than that in the midazolam group, and the incidence of bradycardia in the dexmedetomidine group was significantly higher than that in the midazolam group (P<0.05). At T0∼T4, BIS and MAP showed a decreasing trend in both groups. 12, 24, 36 and 48h postoperatively, the Ramsay sedation score was higher in the dexmedetomidine group than in the midazolam group (P<0.05). At 36 and 48h postoperatively, the serum Cor, E, NE, CRP, TNF-α, and IL-6 levels were lower in the dexmedetomidine group than in the midazolam group (P < 0.05). Compared with the preoperative 1d, the MMSE scores were significantly lower in both groups on one day postoperative, while the MMSE scores were significantly higher at postoperative day 7 than on postoperative day 1 (P < 0.05). At postoperative day 1, the MMSE score was significantly higher in the dexmedetomidine group than in the midazolam group (P < 0.05). The difference in the incidence of adverse events within 72h postoperatively between the two groups was not statistically significant (3.95% vs. 1.28%, χ2=0.284, P = 0.594). Dexmedetomidine compounded with ropivacaine-induced ultrasound-guided thoracic paravertebral nerve block is superior to midazolam for sedation, anti-inflammation, and anti-stress in elderly lung cancer patients.

Transcutaneous Electrical Acupoint Stimulation Improves Postoperative Nutrition and Promotes Early Recovery of Gastrointestinal Function in Patients with Colorectal Cancer

Objective: To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the postoperative nutritional status and recovery of gastrointestinal function in colorectal cancer patients. Methods: Sixty-five patients with ASA grade I-II, undergoing laparoscopic radical colorectal cancer surgery under elective general anesthesia were selected. They were divided into two groups according to the random number table method: the TEAS group (T group) and the sham stimulation group (S group). Two groups of patients were given separate transcutaneous electrical acupoint stimulation and sham stimulation for 30 min at the Hegu (LI4), Neiguan (PC6), Zusanli (ST36), Shangjuxu (ST37), Xiajuxu (ST39), and Sanyinjiao (SP6) points. The intervention time point from the day before surgery, 30 minutes before the start of anesthesia induction, at the start of skin incision, and at the end of surgery to the first, second, and third postoperative days. Changes in serum total protein (TP), albumin (ALB), prealbumin (PA), and transferrin (TRF) were observed, postoperative recovery of gastrointestinal function, and the incidence of postoperative complications were observed. Results: There was no statistical difference between the general data of the two groups; TP, ALB, PA, and TRF in both groups decreased significantly (P&lt;0.05) on postoperative day 1 and 3 compared with those on preoperative day 1. TP, ALB, PA, and TRF were significantly higher in patients in group T than in group S on postoperative days 3 and 7, and the differences were statistically significant (P&lt;0.05). The time to first ventilation, time to defecation, and time to liquid diet were all significantly shorter in group T than in group S. The difference was statistically significant (P&lt;0.05). The incidence of postoperative nausea, vomiting, and abdominal distension was significantly lower in group T than in group S, with a significant statistical difference (P&lt;0.05). Conclusion: Transcutaneous electrical acupoint stimulation can improve postoperative serum protein levels and promote postoperative early recovery in patients with colorectal cancer.

Evaluation of the C-reactive protein serum levels in periodontitis patients with or without atherosclerosis – A clinical study

Background: Periodontitis is a bacterial infection that can originate in the gums and progress to damage the bone and other structures supporting the teeth. One indicator of systemic inflammation caused by various triggers such as injuries, infections, and hypoxia is the highly potent C-reactive protein (CRP). Atherosclerosis is a progressive arterial disease that is characterized by the thickening of subintimal layers in muscular and elastic arteries of intermediate-to-large size due to the accumulation of athermanous plaque. Therefore, our objective in this research is to evaluate CRP levels in individuals with periodontitis, with or without atherosclerosis, after diagnosis. It is important to determine if there is a correlation between periodontitis, a common inflammatory condition of the gums, and elevated CRP levels, which could potentially contribute to the development of atherosclerosis. Methodology: The Department of Periodontics and Implantology at Bhabha College of Dental Sciences conducted the study, which involved the random assignment of 60 participants of both sexes, aged between 30 and 60 years, using a cross-sectional design. The participants were selected from the Department of Periodontics and Implantology, and venous blood samples were taken before and after nonsurgical periodontal treatment to evaluate serum CRP and complete blood count levels. Results: Higher blood CRP levels were seen in individuals with chronic periodontitis, regardless of the presence or absence of atherosclerosis. When comparing the groups of people with and without atherosclerosis and chronic periodontitis, the rise in blood CRP levels was almost double in the group with atherosclerosis. To prevent the progression of atherosclerotic lesions, chronic periodontitis must be treated aggressively. Conclusion: Chronic periodontitis, with or without atherosclerosis, leads to high CRP levels in the blood. Those with both conditions have almost twice the CRP levels compared to those without atherosclerosis. Proper treatment is necessary due to chronic periodontitis’ association with atherosclerotic lesions.

Deficiency of Klotho protein as a cause of linked angina in young patients with thoracalgic phenotype of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in therapeutic practice. Different manifestations of GERD represent different phenotypes of the disease with unique predisposing cofactors and individual pathophysiology. In the continuum of the proposed paradigm, chest pain syndrome in patients with gastroesophageal reflux stands out as a separate phenotype of GERD. Traditionally it was believed that the chest pain in young patients with GERD was not angina. Objective — to study the levels of Klotho protein and nitric oxide in the blood serum of patients with GERD and chest pain (thoracalgic phenotype of GERD). Materials and methods. 64 patients with GERD were prospectively examined, including 27 patients with the thoracalgic phenotype of GERD. The Klotho protein was determined in blood serum by the enzyme immunoassay, the metabolism of NO in the blood plasma was assessed by the Griess test. All patients underwent video esophagogastroscopy, transthoracic echocardiography and 24­Hour Holter electrocardiographic monitoring. Descriptive and nonparametric statistics methods were used in the study. Results. An evaluation of the chest pain syndrome in young patients with GERD revealed a high incidence of linked angina — 25.9%. A decrease in the Klotho protein and NO levels in the blood of patients with GERD and linked angina was observed compared to patients with uncomplicated GERD with pseudo­­coronary pain. The obtained result showed a direct relationship between the concentrations of Klotho protein and NO. Low levels of these parameters in patients with GERD and linked angina reflect endothelial dysfunction and lead to coronary artery spasm mediated by reflux. Conclusions. Linked angina occurs in a quarter of young patients with the thoracalgic phenotype of GERD. The basis of this phenomenon is a decrease in NO synthesis due to endothelial dysfunction, which develops against the background of the Klotho protein deficiency.

Laligurans (Rhododendron arboreum) Enhances Growth, Enzyme Profiles, and Immune Response of Grass Carp Ctenopharyngodon idella (Val. 1844)

ABSTRACTThis study evaluates the effects of Laligurans (Rhododendron arboreum) flowers on the growth performance and health parameters of grass carp (Ctenopharyngodon idella). Known for their anti‐inflammatory properties and medicinal uses, Laligurans flowers were incorporated into diets as an ethanol extract (LGE) and fine powder (LGP) to test their efficacy. A total of 630 grass carp fingerlings (3.07 ± 0.76 g to 3.95 ± 0.85 g) were randomly distributed into 21 nylon cages (1.5 m × 1 m × 2 m) placed in an earthen pond. Seven dietary treatments were administered: a control diet (T1) with standard commercial feed, LGE‐supplemented diets (T2, T3, T4, and T5) at 0.20%, 0.40%, 0.80%, and 1.60% inclusion levels, respectively, and LGP‐supplemented diets (T6 and T7) at 0.20% and 0.40%, respectively. Results demonstrated significant improvements (p &lt; 0.05) in liver, kidney, and blood serum protein levels (total protein, albumin, globulin, and AG ratios) in treated groups compared to the control. Reductions in SGOT, SGPT, and ALP levels were observed in the liver and blood serum of treated groups, while control fish exhibited elevated blood urea nitrogen and creatinine. Fish fed LGE diets showed superior blood profiles compared to those receiving LGP. The T4 group (0.80% LGE) achieved the highest final weight gain, specific growth rate, and survival rate (p &lt; 0.05), highlighting the potential of Laligurans flower extract as a natural immunological and growth‐enhancing supplement in aquaculture diets.

ANALYSIS OF THE EFFECTIVENESS OF BORTEZOMIB-CONTAINING REGIMENS IN PATIENTS WITH MULTIPLE MYELOMA

Introduction. Multiple myeloma is a hematologic malignancy that affects the bone marrow, characterized by the abnormal proliferation of tumor plasma cells. This study aims to assess the effectiveness of a chemotherapy regimen consisting of bortezomib, lenalidomide, and dexamethasone in patients with progressive multiple myeloma, considering negative prognostic factors. Materials and Methods. Group I comprised 23 patients with progressive multiple myeloma who received chemotherapy with bortezomib, lenalidomide, and dexamethasone. The control group (Group II) consisted of 18 healthy individuals. Patients in Group I were examined twice: once before the initiation of treatment and again after completing three courses of chemotherapy. The evaluation included general and biochemical blood analyses, myelogram, immunofixation, and electrophoresis of blood serum and urine proteins, as well as the assessment of monoclonal paraprotein and the level of β2-microglobulin. Treatment response was evaluated according to the criteria set by the International Myeloma Working Group (2016). Results. Among patients receiving chemotherapy as first-line therapy, the overall response rate was 83.33% (15/18), of which a very good partial response was observed in 77.78% (14/18) of patients, a partial response in 5.55% (1/18), and disease progression in 16.67% (3/18) of patients. Specific treatment was associated with a decrease in the level of M-gradient in the blood of patients by 87.6% (p&lt;0.01) and in urine by 96% (p&lt;0.01). A direct correlation was found in Group I between the levels of M-gradient in blood and urine after treatment (r=+0.54; p&lt;0.01 according to Spearman). After three courses of chemotherapy, the levels of total protein and creatinine in the blood serum decreased by 1.2 (p&lt;0.01) and 1.3 times (p&lt;0.05), respectively, compared to the initial examination data. The absence of response in one patient was characterized by an increase in urine M-protein level by 25.7% (0.44 vs. 0.35 g/L) and the presence of plasmacytoma; in the second patient, an increase in blood M-protein content was observed, doubling (11.28 g/L vs. 5.64 g/L). In the third patient, during the second examination, a tumor in the upper part of the sternum on the left with plasmacytic morphology was discovered, which had not been recorded before the start of specific treatment. Conclusion. The presence of plasmacytoma in patients with multiple myeloma may serve as a negative prognostic factor for achieving a response to chemotherapy with bortezomib, lenalidomide, and dexamethasone.

THE ROLE OF Β2-MICROGLOBULIN IN ASSESSING THE PROGRESSION OF B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA

Introduction. The primary assessment of β2-microglobulin holds significant value in monitoring the dynamics of oncohematological processes, which can serve as a crucial marker for evaluating the baseline condition of patients with B-cell chronic lymphocytic leukemia. Aim: to analyze the levels of β2-microglobulin in patients experiencing progression of B-cell chronic lymphocytic leukemia. Materials and methods. Twenty six patients with progressive B-cell chronic lymphocytic leukemia (CLL) were examined, comprising 12 males (46%) and 14 females (54%). These patients were designated as Group I. The control group (Group II) included 20 healthy individuals aged 23–43 years, consisting of 11 females (55%) and 9 males (45%). In Group I, disease staging was assessed using the Rai-Binet classification: stage II (B) was observed in 18 patients (69.2%), stage III (C) in 4 patients (15.4%), and stage IV (C) in 4 patients (15.4%). Among patients with progressive CLL, hyperplastic syndrome was evaluated, including lymph node enlargement (≥3 cm in diameter) and hepato- or splenomegaly (liver or spleen extending ≥5 cm below the costal margin). General and biochemical blood analyses were conducted, along with measurements of β2-microglobulin levels. Statistical methods were applied to process and analyze the data. Results. In patients with progression of B-cell chronic lymphocytic leukemia (CLL), hematological analysis revealed anemia (hemoglobin &lt;100 g/L) in 6 patients (23.1%) and thrombocytopenia in 8 patients (30.7%). Leukocytosis with leukocyte levels &gt;100 G/L was observed in 4 patients (15.4%) in Group I. Notably, an inverse correlation was identified between β2-microglobulin levels and hemoglobin levels (r = -0.52; p = 0.02). Biochemical analysis showed a reduction in total serum protein to grade 1 according to CTCAE in 2 patients (7.7%), elevated serum creatinine levels, reaching grade 1 according to CTCAE, were observed in 4 patients (15.4%) in Group I. An inverse correlation was found between β2-microglobulin levels and total serum protein levels (r = -0.44; p = 0.02). A direct correlation was also identified between β2-microglobulin levels and serum creatinine levels (r = 0.65; p = 0.04). In 9 (34.7%) patients of group I, the concentration of β2-microglobulin in blood serum exceeded the level of 5 mg/l. It is important that all 100% (9/9) of patients in this category were found to have hyperplastic syndrome. In addition, 33.3% (3/9) of patients had a combination of lymphadenopathy, splenomegaly, and hepatomegaly (liver +5 cm below the edge of the costal arch), 55.6% (5/9) had a combination of two factors, in 11, 1% (1/9) hyperplastic syndrome was characterized by an increase in the size of peripheral lymph nodes by more than 3 cm. The average level of β2-microglobulin was 6.24 mg/l in patients with progression of B-cell chronic lymphocytic leukemia of group I, of which 9 patients had a level of β2-microglobulin greater than 5 mg/l. Conclusion. The level of β2-microglobulin corresponds to the severity of progression of B-cell chronic lymphocytic leukemia and correlates with the level of anemia, hypoproteinemia, hypercreatinemia, and the severity of hyperplastic syndrome.

Predictors of rituximab efficacy in systemic sclerosis-associated interstitial lung disease: machine-learning analysis of the DESIRES trial

Abstract Objectives Rituximab is emerging as a promising therapeutic option for systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, little is known about factors that predict the efficacy of rituximab in SSc-ILD. Methods A post-hoc analysis was performed on prospective data from 48 patients with SSc-ILD in the double-blind, randomized, placebo-controlled DESIRES trial. A total of 28 baseline factors were selected as candidates to predict the efficacy of rituximab on the percentage of predicted forced vital capacity (ppFVC) at 24 weeks. A machine learning causal tree algorithm was used to explore the combination of predictors to identify subpopulations with a good response to rituximab. Results Serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6) were selected as branches of the decision tree to stratify patients into 3 subpopulations. In the subpopulation with serum CRP levels ≥ 0.055 mg/dl, ΔppFVC was significantly higher in the rituximab group than in the placebo group (difference 8.01% [95% CI: 4.40%, 11.62%]). In the subpopulation with serum CRP levels &amp;lt; 0.055 mg/dl and serum KL-6 levels ≥ 364 U/ml, ΔppFVC was comparable between the two groups (difference 2.47% [95% CI: -1.99%, 6.92%]). In the subpopulation with serum CRP levels &amp;lt; 0.055 mg/dl and serum KL-6 levels &amp;lt; 364 U/ml, ΔppFVC was significantly lower in rituximab than in placebo (difference -6.85% [95% CI: -10.80%, -2.91%]). Conclusion Even slight elevations in serum CRP levels are associated with the improvement in ppFVC and may serve as predictors of rituximab efficacy in SSc-ILD.

Dietary supplementation of compound probiotics to improve performance, egg quality, biochemical parameters and intestinal morphology of laying hens.

The purpose of this study was to investigate the effects of dietary supplementation of compound probiotics on the performance, egg quality, biochemical parameters and intestinal morphology of laying hens. A total of 180 healthy 200-day-old Hyline Brown laying hens with similar initial laying rate (87.5% ± 0.2%) were randomly divided into the control group and the treatment group. Each group included 6 replicates and each replicate included 15 laying hens. The control group was provided a basal diet, while the treatment group received the basal diet supplemented with compound probiotics. The experiment lasted for 52 days. The study indicated the following outcomes: (1) The laying rate (LR) and average egg weight (AEW) of laying hens in the treatment group were significantly higher than those of the control group (p < 0.05), whereas the feed-to-egg ratio (F/E) was significantly lower (p < 0.05); (2) The yolk weight (YW), egg shape index (ESI) and albumen height (AH) were significantly higher (p < 0.05), whereas the eggshell percentage (EP) was significantly lower (p < 0.05) after the dietary supplementation of compound probiotics; (3) The treatment group significantly decreased in total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), immunoglobulin A (IgA), and immunoglobulin G (IgG) levels in serum compared to the CON group (p < 0.05). Additionally, serum levels of total protein (TP), globulin (GLB), albumin (ALB), high-density lipoprotein (HDL), alkaline phosphatase (ALP), and total antioxidant capacity (T-AOC) were significantly higher in the treatment group (p < 0.05); (4) The supplementation of compound probiotics to laying hen diets led to a significant reduction in crypt depth (CD) and the ratio of villus height to crypt depth (V/C) in the jejunum compared to the CON group (p < 0.05). In conclusion, the supplementation of compound probiotics can regulate the body metabolism and improve the intestinal morphology, thus enhancing the antioxidant capacity and immune function of the body, which in turn improves the performance and egg quality of laying hens.

Genetic Investigation of Regulatory Regions of MKRN3 and DLK1 Genes in Children with Central Precocious Puberty.

Most of the loss-of-function mutations described in children with central precocious puberty (CPP) is located into the coding regions of MKRN3 or DLK1 genes. Notably, potential abnormalities in the regulatory regions of these CPP-genes are rarely explored. To search for pathogenic variants in the regulatory regions of MKRN3 and DLK1 genes in patients with familial or idiopathic CPP. A cohort of 217 individuals with CPP (205 girls and 12 boys; 143 sporadic cases and 74 familial cases) was investigated. Rare and potentially pathogenic variants in the coding regions of both genes were previously excluded. Analyses of the regulatory regions of MKRN3 and DLK1 were performed using polymerase chain reaction and direct automated sequencing (Sanger method). Circulating serum levels of MKRN3 and DLK1 proteins were measured using ELISA assay. We identified a heterozygous allelic variant (c.-265G>A), previously associated with CPP, located in the promoter region of the MKRN3 gene in three girls from two unrelated families. In silico prediction analysis indicated that the c.-265G>A variant was in the ZNF384 binding region. ZNF384 gene encodes a C2H2-type zinc finger protein, which might act as a transcription factor. MKRN3 serum levels varied from 197.5 pg/mL to 1,907 pg/mL and were relatively lower in patients with CPP who carried the c.-265G>A variant. No pathogenic allelic variant was found in the regulatory region of the DLK1 gene. Pathogenic variants in the regulatory region of MKRN3 gene are rare and can be associated with the CPP phenotype.

Effect of Arsenic Exposure on AS3MT Protein Levels in Serum of Type 2 Diabetic Patients Compared to Non-diabetics.

This research explores the impact of arsenic exposure on serum protein profiles in type 2 diabetes patients, with an emphasis on the AS3MT protein as a biomarker. Utilizing Bradford protein assay, SDS-PAGE, HPLC, and mass spectrometry, we quantified and analyzed variations in serum protein levels, focusing on differences between control groups (82.94 ± 8.03µg/mL) and diabetic patients (96.95 ± 5.02µg/mL) of high arsenic exposed in areas Kasur and Lahore, Punjab, Pakistan. The study revealed a significant increase in total serum proteins and specifically identified elevated levels of AS3MT in the diabetic group compared to controls. By using 15% gel, proteins were separated, and bands were visible at 42KD. Further investigations using HPLC provided a detailed chromatographic profile of AS3MT, isolating this protein effectively and displaying its heightened abundance through a marked peak within the sample chromatograms. Additionally, intact mass and tryptic digestion profiles analyzed by mass spectrometry (molecular weight of 41,747.79 D) further corroborated the identity and modification of AS3MT in the context of arsenic exposure. ELISA was used for the quantification of AS3MT protein concentration, and a 260% increase was confirmed in the diabetic group exposed to arsenic. These findings suggested that arsenic exposure significantly alters AS3MT protein and serum protein levels in diabetic patients, supporting the hypothesis that AS3MT can serve as a biomarker for arsenic-induced diabetic conditions.

Effects of idebenone on cognitive function and serum biomarkers in patients with amnestic mild cognitive impairment

ObjectivesThis retrospective study aimed to investigate the effects of idebenone on cognitive function and serum levels of superoxide dismutase (SOD) and high-sensitivity C-reactive protein (hs-CRP) in individuals with amnestic mild cognitive impairment (aMCI).MethodsRetrospective data were collected from the Neurology outpatient department of Liaocheng People’s Hospital from January 2021 to June 2023. Patients with a newly diagnosed aMCI who received treatment were included in the idebenone treatment group. The treatment group took 30 mg of oral idebenone three times a day for 6 months. A control group of 51 MCI patients who did not receive cholinesterase inhibitors or other cognitive-enhancing drugs during the period was selected. Cognitive function assessments and serum Biomarkers were conducted before and after treatment in both groups.ResultsMoCA scores were significantly improved after 6 months of idebenone treatment, and the difference was statistically significant. The delayed recall score was significantly improved, and the difference was statistically significant; The level of SOD increased and the level of high-sensitivity C-reactive protein decreased after the treatment, but there was no significant change in the control group.ConclusionsThe results of this study demonstrate that idebenone treatment significantly improves cognitive function in individuals with aMCI, particularly in the domain of delayed memory. In addition, idebenone reduces the degree of inflammation and oxidative stress and improves antioxidant levels. These findings suggest that idebenone may be a promising intervention for the management of cognitive impairments associated with aMCI.Graphical

Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma

BackgroundRetroperitoneal liposarcoma (RLPS) is a mesenchymal malignant tumor characterized by different degrees of adipocytic differentiation. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes of RLPS, exhibiting clear differences in biological behaviors and clinical prognosis. The metabolic features and genomic characteristics remain unclear.MethodsThis study employed lipidomic and RNA-seq analyses of RLPS tissues from 19 WDLPS and 29 DDLPS patients. Western blot and immunohistochemistry staining were performed to verify the tumor tissue protein levels of TIMP1, FN1, MMP11, GPNMB, and ECM1. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate different serum protein levels in 128 blood samples from patients with RLPS. Multivariate analysis was performed to identify the most crucial variables associated with overall survival (OS) and recurrence-free survival (RFS) of the RLPS patients.ResultsLipidomic analysis revealed a significant difference in lipid metabolism, particularly in phosphatidylcholines and triacylglycerides metabolism. RNA sequencing analysis revealed that 1,630 differentially expressed genes (DEGs) were significantly enriched in lipid metabolism, developmental process, and extracellular matrix (ECM) pathways. Integrated lipidomic and transcriptomic analysis identified 29 genes as potential biomarkers between WDLPS and DDLPS. Among the 29 DEGs, we found that TIMP1, FN1, MMP11, GPNMB, and ECM1 were increased in DDLPS tumor tissues than in WDLPS tumor tissues. The receiver operating characteristic (ROC) curve showed high specificity and sensitivity in diagnosing patients using a five-gene combination (AUC = 0.904). ELISA revealed a significant increase in the serum levels of ECM1 and GPNMB in patients with DDLPS compared to patients with WDLPS. ECM1 increased progressively across different FNCLCC Grades, correlating negatively with RFS (P = 0.043). GPNMB levels showed a negative correlation with OS (P = 0.019).ConclusionsOur study reveals different lipid metabolism, several transcriptional pathways between WDLPS and DDLPS, and examines several serum markers associated with the prognosis of RLPS. These findings provide a vital basis for future endeavors in diagnosing and predicting the prognosis of retroperitoneal liposarcoma with different differentiations.

Serum Levels of Lead and Selected Acute Phase Proteins in Patients with Substance Use Disorders

Background: Chronic inflammation, immune system dysfunction and elevation in the levels of toxic metals such as lead (Pb) are common observations in patients with substance use disorders (SUD). However, there is little information on the acute phase profile of SUD patients with different serum levels of Pb. Therefore, serum levels of selected acute phase proteins in SUD patients with different serum levels of Pb were determined in this study. Methods: A total of 84 adults consisting of 45 patients with SUDs and 39 controls were enrolled into this case-control study. Serum levels of Pb, albumin and C-reactive protein (CRP) were determined using Atomic Absorption Spectrophotometer, bromocresol green (BCG) colorimetric method, and ELISA, respectively. Thereafter, CRP-albumin ratio (CAR) was calculated as appropriate. Results: Serum levels of Pb and albumin were significantly higher in patients with SUDs compared with the controls. Considering variation in acute phase proteins based on Pb level, the serum level of albumin was significantly lower, while the serum CRP level and CAR were slightly higher in patients with SUDs whose Pb level was higher than 5 µg/dL compared with patients whose Pb level was ≤5 µg/dL. No significant differences were observed in the levels of Pb, albumin, CRP, CAR in patients with SUDs who abuse single substance compared with those who abuse multiple substances. Conclusion: SUD is associated with increased serum levels of Pb and albumin, and alteration in the serum levels of acute phase proteins appears to be influenced by the serum Pb level. Therefore, there is the need for routine measurement of Pb level in patients with SUDs as they could benefit from therapeutic interventions involving chelation of Pb which could prevent disordered acute phase responses in the patients and facilitate optimal response to antipsychotics.

Evaluating TAB2, IKBKB, and IKBKG Gene Polymorphisms and Serum Protein Levels and Their Association with Age-Related Macular Degeneration and Its Treatment Efficiency.

Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of blindness, affecting millions worldwide. Its pathogenesis involves the death of the retinal pigment epithelium (RPE), followed by photoreceptor degeneration. Although AMD is multifactorial, various genetic markers are strongly associated with the disease and may serve as biomarkers for evaluating treatment efficacy. This study investigates TAB2 rs237025, IKBKB rs13278372, and IKBKG rs2472395 variants and their respective serum protein concentrations in relation to AMD occurrence and exudative AMD treatment response to anti-VEGF treatment. Materials and Methods: The case-control study involved 961 individuals, and they were divided into three groups: control, early AMD, and exudative AM patients. Genotyping of selected SNPs were conducted using a real-time polymerase chain reaction method (RT-PCR). Based on the clinical OCT and BCVA data, patients with exudative AMD were categorized into one of two groups: responders and non-responders. The data obtained were analyzed using the "IBM SPSS Statistics 29.0" software program. Results: Our study revealed that TAB2 rs237025 allele A was identified as a risk factor for early and exudative AMD development. The same associations remained only in females with exudative AMD but not in males, suggesting gender-specific pathogenetic pathways in exudative AMD. Analysis of IKBKB rs13278372 or serum IKBKB protein associations with early or exudative AMD occurrence in the Lithuanian population revealed no significant associations. On the other hand, we found that each A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment (OR = 0.347; 95% CI: 0.145-0.961; p = 0.041). These results suggest a potential marker for future studies evaluating anti-VEGF treatment for exudative AMD patients. IKBKG rs2472395 was a protective variant for early AMD in males and for exudative AMD in females only. Also, IKBKG protein concentration was lower in exudative AMD relative to the control group (median (IQR): 0.442 (0.152) vs. 0.538 (0.337), p = 0.015). Moreover, exudative AMD patients who carry the GG genotype of IKBKG rs2472394 exhibited significantly reduced serum IKBKG concentrations compared to the controls (median (IQR): 0.434 (0.199) vs. 0.603 (0.335), p = 0.012), leading to the hypothesis that the IKBKG rs2472394 variant might play a role in protein concentration differences and exudative AMD development. Conclusions: Our study identified the TAB2 rs237025 allele A as a significant risk factor for both early and exudative AMD, with gender-specific associations observed in females with exudative AMD, suggesting distinct pathogenetic pathways. While IKBKB rs13278372 and serum IKBKB protein levels showed no significant association with AMD development, the A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment, indicating its potential as a marker for treatment outcomes. Additionally, the IKBKG rs2472395 variant was found to be protective for early AMD in males and exudative AMD in females, and lower IKBKG protein levels were associated with exudative AMD, particularly in patients with the GG genotype of IKBKG rs2472394, suggesting its role in protein concentration and disease progression. These findings highlight genetic markers that may contribute to AMD pathogenesis and treatment response.

Tralokinumab Treatment in Adult Atopic Dermatitis Patients: 28-Week Evaluation of Clinical Effectiveness, Safety, Serum Proteins and Total IgE Levels.

Tralokinumab-a biological that specifically targets interleukin-13-is one of the newer advanced systemic treatments for patients with moderate-to-severe atopic dermatitis (AD). Although safety and efficacy have been shown in phase-III clinical trials, daily practice data are needed. Therefore, the aim of this study was to evaluate 28-week safety and effectiveness, serum proteins and total IgE levels in adult AD patients treated with tralokinumab in daily practice. Data of all adult AD patients who started treatment with tralokinumab and participated in the BioDay registry were collected at baseline, and after 4,16 and 28 weeks of treatment. Clinical efficacy was evaluated by clinical outcome measures, such as the Eczema Area and Severity Index (EASI) as well as patient-reported outcome measures, such as the numerical rating scale (NRS) for pruritus. Adverse events were evaluated. In a subgroup of patients, 18 proteins as well as total IgE levels were measured in serum. A total of 84 patients were included, of whom 39 were dupilumab-naïve (D-naïve) and 45 were dupilumab non-naïve (D-non-naïve) patients. All primary outcomes significantly improved during 28 weeks of tralokinumab treatment and the probability of achieving EASI ≤ 7 and NRS-pruritis ≤ 4 was 75.8% (56.9-88.2) and 51.4% (28.0-74.2), respectively. The disease severity-associated proteins TARC/CCL17 and PARC/CCL18 decreased during treatment, and total IgE levels significantly decreased in the D-naïve patients. The most reported adverse events were eye disorders (n = 24, 28.6%). A total of 23 patients (27.4%) discontinued treatment due to adverse events and/or ineffectiveness, with hair loss being the most common adverse event leading to treatment discontinuation (n = 6). Tralokinumab is an effective treatment for moderate-to-severe AD in adult patients, in both dupilumab-naïve patients and patients who previously failed on dupilumab treatment. The clinical effect is supported by the biological data.

Effect of Chromium Supplementation on Serum Levels of Inflammatory Mediators: An Updated Systematic Review and Meta-analysis on Randomized Clinical Trials.

Chromium has been recognized for its beneficial effects on inflammation reduction; therefore, we conducted a systematic review and meta-analysis to find the effect of chromium supplementation on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in subjects aged 18years and older. Related articles were identified by searching databases such as the Cochrane Library, ClinicalTrials.gov, ISI Web of Science, Scopus, and PubMed up until Agust 2024. We computed the mean differences (MD) along with their standard deviations (SDs) to carry out the meta-analysis. Statistical heterogeneity of the intervention effects was assessed using I-squared statistics and Cochran's Q test. In total, twelve and eleven studies were included in the present systematic review and meta-analysis, respectively. The pooled results indicated that the differences in serum levels of CRP and TNF-α between chromium group and the comparison group were statistically significant (CRP: weighted mean difference (WMD) = -0.58mg/L; 95% confidence interval (CI) = -0.95, -0.22mg/L; P = 0.002; TNF-α: WMD = -1.22pg/ml; 95% CI = -1.91, -0.53pg/ml; p = 0.001). In contrast, chromium supplementation resulted in a non-significant decrease in serum levels of IL-6 (WMD = -0.63pg/ml; 95% CI: -1.67, 0.4pg/ml; P < 0.001). Our study supports the beneficial effect of chromium supplementation on serum concentration of CRP and TNF-α, but our results showed that chromium supplementation non-significantly reduced the serum levels of IL-6. However, it seems that chromium formulation, participants' BMI, sample size, and geographical region are strong variables that predict the effect of chromium supplementation on inflammatory mediators.