Serum Protein Research Articles

Abstract A050: The impact of air pollution on aggressive breast cancer prognoses in women of African descent

Abstract Significance. Breast cancer (BC) is the most diagnosed cancer among women in the US. Though highly heterogeneous, different subtypes can be characterized by the expression of membrane receptors on the cell surface: ER+, HER2+, PR+, or basal-like which does not express any of the three receptors. Basal-like triple-negative breast cancer (TNBC) is a highly aggressive subtype of BC that represents about 15% of overall BC cases. Black women disproportionately experience higher rates of early-onset TNBC phenotypes and worse prognoses when compared to White women. Though genetics is a key factor in oncogenesis and cancer progression, it is now widely recognized that differences in cancer outcomes are influenced, also, by various environmental, social, and lifestyle factors known collectively as the social determinants of health (SDOH). For example, air pollution has consistently been shown to be associated with an increased risk of breast cancer, however, little is known about how air pollution alters biological and molecular mechanisms impacting breast cancer progression. Elucidating these influential factors is critical to understanding and addressing disparate outcomes. We are interested in understanding how air pollution impacts immune-oncology related proteins in breast cancer, specifically for Black and White women living in Baltimore City, Maryland. Methods. In a cohort of 217 women (142 Black, 75 White), we performed statistical analyses to determine the correlation between particulate matter 2.5 (PM2.5) with breast cancer subtype and oncogenic molecular drivers within the tumor and its microenvironment. PM2.5 concentration for Census year 2000 was measured using the EPA Downscale Model. Concentrations at the census-tract level were then linked to each participant's geocoded residential address at study baseline. Results. [BJ1] Our data reveal that a higher exposure to PM2.5 is correlated with breast cancer subtypes incidences[BJ2] (p- value[BJ3] =0.051), specifically for hormone receptor positive (ER+ and/or PR+) and TNBC subtypes (p-value=0.035). Elevated air pollution is also associated with estrogen-receptor status overall (p-value=0.002) and in Black (p-value=0.043) and White (p-value=0.008) women in the stratified analysis. Serum protein measurements in this cohort also revealed significant relationships between elevated air pollution and immune-oncology related proteins, including PD-L1, CAIX, CXCL9, and MCP-2.Discussion. Our preliminary evidence reveals an association between air pollution, breast cancer subtypes, and immune-oncology related proteins, with some of these relationships affecting Black and White populations differently. We will continue to interrogate these differences and begin to reveal the underlying mechanisms exacerbating breast cancer disparities. Citation Format: Kayla S. Ingram, Brittany Jenkins-Lord. The impact of air pollution on aggressive breast cancer prognoses in women of African descent [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A050.

Revolutionizing cancer therapy: nanoformulation of miRNA-34 - enhancing delivery and efficacy for various cancer immunotherapies: a review.

Despite recent advancements in cancer therapies, challenges such as severe toxic effects, non-selective targeting, resistance to chemotherapy and radiotherapy, and recurrence of metastatic tumors persist. Consequently, there has been considerable effort to explore innovative anticancer compounds, particularly in immunotherapy, which offer the potential for enhanced biosafety and efficacy in cancer prevention and treatment. One such avenue of exploration involves the miRNA-34 (miR-34) family, known for its ability to inhibit tumorigenesis across various cancers. Dysregulation of miR-34 has been observed in several human cancers, and it is recognized as a tumor suppressor microRNA due to its synergistic interaction with the well-established tumor suppressor p53. However, challenges have arisen with the therapeutic application of miR-34a. These include its susceptibility to degradation by RNase in serum, limiting its ability to penetrate capillary endothelium and reach target cells, as well as reports of immunoreactive adverse reactions. Furthermore, unexpected side effects may occur, such as the accumulation of therapeutic miRNAs in healthy tissues due to interactions with serum proteins on nano-vector surfaces, nanoparticle breakdown in the bloodstream due to shearing stress, and unsuccessful extravasation of nanocarriers to target cells owing to interstitial fluid pressure. Despite these challenges, miR-34a remains a promising candidate for cancer therapy, and other members of the miR-34 family have also shown potential in inhibiting tumor cell proliferation. While the in vivo applications of miR-34b/c are limited, they warrant further exploration for oncotherapy. Recently, procedures utilizing nanoparticles have been developed to address the challenges associated with the clinical use of miR-34, demonstrating efficacy both in vitro and in vivo. This review highlights emerging trends in nanodelivery systems for miR-34 targeting cancer cells, offering insights into novel nanoformulations designed to enhance the anticancer therapeutic activity and targeting precision of miR-34. As far as current knowledge extends, no similar recent review comprehensively addresses the diverse nanoformulations aimed at optimizing the therapeutic potential of miR-34 in anticancer strategies.

Cellulose acetate electrophoretic separation of serum and urine proteins in Nigerian children with autism spectrum disorders

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by social communication challenges and restricted, repetitive behaviors. While genetic and environmental factors are known to contribute to ASD, the role of the immune system remains unclear. This study investigated the separation patterns of serum and urine proteins in Nigerian children with ASD compared to typically developing children and children with other NDDs.MethodsForty-seven participants aged 3–8 years were recruited, including 16 children diagnosed with ASD and 16 children with other NDDs, both according to DSM-5 criteria, along with 15 neurotypical children. Blood and urine samples were collected for protein analysis. Total protein and albumin levels were measured in both serum and urine using established methods. Protein separation in serum and urine was performed using cellulose acetate electrophoresis, followed by densitometry analysis of the electrophoretic patterns.ResultsThe results revealed no significant differences in total serum protein levels and most protein fractions between the groups. However, children with other NDDs exhibited significantly lower levels of alpha-2 globulin compared to neurotypical children. Conversely, both ASD and NDD groups showed significantly higher gamma globulin levels compared to the control group. Interestingly, spot urine protein levels were significantly higher in children with ASD compared to neurotypical children.ConclusionThe observed changes in alpha-2 and gamma globulin levels suggest potential immune system involvement in ASD and other NDDs. The higher urine protein excretion in the ASD group warrants further investigation to explore the potential of urinary protein biomarkers for ASD diagnosis.

Impact of Toxoplasma gondii on Serum Protein Levels and Mineral Content in Sheep and Goats at a Small Dairy Farm in White Nile State, Sudan

Aim: This study aims to investigate the effects of Toxoplasma gondii infection on the serum proteins and macro elements (Sodium, Potassium, Calcium, Magnesium and Phosphate) for sheep and goat. Introduction: In sheep and goats, Toxoplasma infection is a major cause of abortion and stillbirth. Subclinical infections are also quite common in adult animals of affected flocks and herds. Serum proteins and macro elements plays an essential role in animal metabolism. Materials and Methods: Serological survey of T. gondii was conducted using Latex Agglutination Test (LAT) for 20 sera collected from sheep and goats (8 and12 respectively) in white Nile State, Sudan. Results: Out of twelve goats’ serum and eight sheep serum samples, seven samples were found to be positive for Toxoplasma (58.33%) in goats and four samples were found to be positive for Toxoplasma (50%) in sheep, the remaining samples were negative. It was observed that serum Total protein (Tp) level was increased significantly (p<0.05) in both species, and albumin (Alb) level decreased significantly (p<0.05) in goats, while Globulin (Glob) was significantly (p<0.05) low in sheep compared with control animals. The results showed that some minerals (Na and K) concentrations in the serum were higher in both sheep and goats compared to the controls. Conclusion: In conclusion infestation of goats with Toxoplama gondii increases the total protein, globulins and significantly decreases the albumin concentrations. For sheep the infestation increases the total protein, albumin and significantly decreases the globulin concentrations. Sheep and goats infected with Toxoplasma gondii showed increased serum sodium, potassium and magnesium levels affecting most of the enzyme systems.

Harnessing the Potential of Whey in the Creation of Innovative Food Products: Contributions to the Circular Economy

Food waste and by-products are intricately linked to sustainable food production, as reducing waste can play a significant role in achieving a more sustainable and efficient food system. Sustainable utilization and recovery of by-products can significantly contribute by creating strategies that can lead to cost savings and increased efficiency across the food supply chain. Worldwide, more than 40% of whey from cheese production is discarded, resulting in the loss of valuable nutrients and potentially polluting the environment. Effective use of whey reduces environmental impact and enhances manufacturing sustainability. Thus, a circular approach to food waste management in the dairy industry supports sustainability goals and creates opportunities for innovation. Whey contains most of the soluble components of milk, including a large number of serum proteins and all the essential amino acids, making it suitable for producing beverages with high nutritional value. This study aims to produce whey-based beverages with different additions to obtain dairy products with high nutritional value. Three different ingredients, sea buckthorn, ginger, and cinnamon, were chosen for their numerous health benefits to the consumer. Six samples were prepared utilizing both unmodified and deproteinized whey in a 75% proportion, with the addition of 25% sea buckthorn juice, 0.75% ginger juice, and 0.2% cinnamon powder. The resultant samples were packaged in 200 mL bottles and maintained at a controlled temperature of 6 °C to ensure optimal preservation. Given the paramount importance of consumer acceptability in novel beverage development, a comprehensive evaluation was conducted to assess the sensory properties of the formulated beverages. In addition, physico-chemical properties and their evolution over 14 days of storage were examined. The sample containing whey, sea buckthorn juice, ginger juice, and cinnamon powder received the highest marks from the tasters. The values of the physico-chemical parameters varied depending on the type of whey used and the storage period. Thus, a pH of approximately 5 and an acidity between 30 and 80 °T were recorded. The average lactose content was 4%, the average protein content was 2.5%, and the total soluble solids content was 11.5 °Brix. The beverages developed in this study represent viable alternatives for diversifying food production through sustainable, environmentally friendly technological variants. By applying circular economy principles, these products contribute to reducing food waste in the dairy industry.

The anti-angiogenic, anti-inflammatory and anticoagulant potential of a polysaccharide extracted from the brown alga Cystoseira humilis

The present study aimed to evaluate the properties of a sulfated polysaccharide (PSCH) extracted from the brown alga Cystoseira humilis. We analyzed the chemical composition, anti-angiogenesis activities, anticoagulant, and anti-inflammatory effects of the PSCH, using various techniques encompassing UV–visible spectroscopy, fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (X-RD), scanning electron microscopy (SEM), steric exclusion chromatography (SEC) and high-performance liquid chromatography coupled to refractive index detector (HPLC-RID). The study found that PSCH was a sulfated heteropolysaccharide consisting of glucuronic acid, arabinose, galacturonic acid, xylose and fructose, and has a semi-crystalline nature with a molecular weight of about 379.44 kDa. The PSCH contains 41.77 % carbohydrates, 12.33 % proteins, and 4.59 % sulfates. The PSCH fraction has anti-angiogenic potential highlighted through assays on the chorioallantoic membrane, where vascular branching was inhibited by about 41.65 % and 61.38 % at concentrations of 50 and 100 μg/egg, respectively, compared to the untreated group. PSCH displayed an anti-edematous effect in vivo by reducing malondialdehyde and advanced oxidation protein products in paw tissue after five hours of carrageenan injection. When rats were co-treated with PSCH, there was evidence of a significant increase in antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase, and glutathione) in edematous paw tissues compared to untreated rats. Furthermore, PSCH significantly influenced hematological parameters and the rate of anti-inflammatory serum protein fractions compared to the inflamed group. Interestingly, PSCH may exhibit anticoagulant properties by extending activated partial thrombosis time, thrombin time and prothrombin time. The present study has shown that Cystoseira humilis polysaccharides have antioxidant, anti-angiogenic, anti-inflammatory, and anti-coagulant properties, making them suitable for therapeutic purposes.

The Roles of Immune Molecules in the Acute Post-Transplant Period

Purpose: Renal transplantation is a therapeutic choice that enhances the quality of life for patients suffering from end-stage renal failure. The objective of this study was to ascertain the alterations in the levels of immune molecules following transplantation and to examine the correlation between these changes and the medical records of the patients. Material and Methods: The gene expression of an immune molecule panel (FOXP3, TNF-α, IFN-γ, IL-18, IL-6, IL-17a, IL-12a, IL-2, IL-10, and TGF-β) in peripheral blood specimens of 30 kidney transplant patients was determined by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method with SYBR Green Dye. The serum proteins were quantified using Enzyme-Linked ImmunoSorbent Assay (ELISA). Results: TGF-β exhibited the most significant alteration in gene expression levels compared to the levels before transplanting (p

Genetic evidence for efficacy of targeting IL-2, IL-6 and TYK2 signalling in the prevention of type 1 diabetes: a Mendelian randomisation study.

We aimed to investigate the genetic evidence that supports the repurposing of drugs already licensed or in clinical phases of development for prevention of type 1 diabetes. We obtained genome-wide association study summary statistics for the risk of type 1 diabetes, whole-blood gene expression and serum protein levels and investigated genetic polymorphisms near seven potential drug target genes. We used co-localisation to examine whether the same genetic variants that are associated with type 1 diabetes risk were also associated with the relevant drug target genetic proxies and used Mendelian randomisation to evaluate the direction and magnitude of the associations. Furthermore, we performed Mendelian randomisation analysis restricted to functional variants within the drug target genes. Co-localisation revealed that the blood expression levels of IL2RA (encoding IL-2 receptor subunit α [IL2RA]), IL6R (encoding IL-6 receptor [IL6R]) and IL6ST (encoding IL-6 cytokine family signal transducer [IL6ST]) shared the same causal variant with type 1 diabetes liability near the corresponding genes (posterior probabilities 100%, 96.5% and 97.0%, respectively). The OR (95% CI) of type 1 diabetes per 1-SD increase in the genetically proxied gene expression of IL2RA, IL6R and IL6ST were 0.22 (0.17, 0.27), 1.98 (1.48, 2.65) and 1.90 (1.45, 2.48), respectively. Using missense variants, genetically proxied TYK2 (encoding tyrosine kinase 2) expression levels were associated with type 1 diabetes risk (OR 0.61 [95% CI 0.54, 0.69]). Our findings support the targeting of IL-2, IL-6 and TYK2 signalling in prevention of type 1 diabetes. The analysis code is available at https://github.com/jkoskenniemi/T1DSCREEN , which also includes instructions on how to download the original GWAS summary statistics.

THE RECOMBINANT BACTERIA LACTOCOCCUS LACTIS EXPRESSING SARS-COV-2 SPIKE PROTEIN OR ITS RECEPTOR-BINDING DOMAIN ELICITS AN IMMUNE RESPONSE FOLLOWING ORAL IMMUNISATION OF RATS

Mucosal delivery of antigens represents an effective strategy for the development of vaccines to control diseases with the upper respiratory and/or gastrointestinal tracts as the main routes of transmission. Lactic acid bacteria (LAB) are food-grade bacteria used for the expression of target antigens in the development of mucosal vaccines. Over the last two decades, research on the use of LAB has focused on the construction of genetically modified strains. Current study aimed to develop and examine the recombinant Lactococcus lactis strains, expressing SARS-CoV-2 spike (S) protein or the receptor-binding domain (RBD) of S protein as immunizing antigens.The spike gene from the component II of Sputnik V vaccine and two synthesized coding sequences of the RBD region of SARS-CoV-2 spike protein (319–529 residues named HA-spike and 318–590 residues named mini-spike) were subcloned into expression vector pNZ8121. The resulting plasmids were verified by sequencing and subsequently transformed into competent L. lactis NZ3900 cells. The expression of recombinant proteins in obtained strains was analyzed by western blot using SARS-COV-2 Spike RBD antibodies. The results showed that the spike gene could be efficiently expressed in the cells of recombinant L. lactis. The major 150 kDa band detected in the cell lysate of L. lactis pNZ::spike represented the full-length S protein. Protein bands of 35 kDa and 23 kDa from the lysates of L. lactis pNZ::mini-spike and L. lactis pNZ::HA-spike respectively were detected indicating that the recombinant RBD protein was also successfully expressed. The mini-spike was expressed more abundantly than the HA-spike variant. Based on the growth kinetics and protein expression profiles of recombinant strains, the highest protein yield was obtained under the following conditions: overnight culture was inoculated (1/25 inoculum) and grown until reaching an optical density of 0,9 at 600 nm, then gene expression was induced by adding nisin (1 ng/ml), cells were harvested after 3 h incubation with the inducer. To examine the immunogenicity of recombinant strains, 1 ml of cell suspension (1,5×109 CFU) of L. lactis pNZ::spike, pNZ::mini-spike or L. lactis pNZ::HA-spike was orally administered to Wistar rats. The same volume of peptone water was administered to the control group. Serum was collected from the animals at 28 days and IgG level was determined by ELISA for the quantitative determination of IgG antibodies to SARS-CoV-2 (COVID-19) Spike RBD protein in rat serum. As expected, the serum from control animals lacked antibodies to the RBD antigen. The serum of rats immunised once with cell suspension of the recombinant strains showed the following levels of specific IgG: 124,24±12,56 ng/ml in group pNZ::mini-spike, 165,91±59,13 ng/ml in group pNZ::spike, and 213,60±54,08 ng/ml in group pNZ::HA-spike. The highest IgG level (545,56±230,24 ng/ml) was detected in the serum of rats immunized with ultrasound-treated cell suspension of L. lactis pNZ::spike. No adverse effects were observed in vaccinated animals at regular check-ups throughout the study period.The current results have demonstrated that the RBD and full spike protein were successfully expressed in L. lactis. Oral administration of the recombinant L. lactis expressing S protein or RBD to rats appeared to generate the anti-SARS-CoV-2 antibodies in serum, positioning this bacteria as promising basis for creating oral vaccine.

Evaluation of Serum Proteome Sample Preparation Methods to Support Clinical Proteomics Applications.

Serum contains several proteins that are associated with disease-related processes. Mass spectrometry (MS)-based proteomics approaches greatly facilitate serum protein biomarker development. However, the serum proteome complexity presents a technical challenge for the accurate, sensitive, and reproducible quantification of proteins by MS. Thus, efficient sample preparation methods are of critical importance for serum proteome analyses. In this study, we evaluated the technical performance of two serum proteome sample preparation methods using sera from patients with high-grade serous ovarian cancer and patients with benign nongynecological conditions with a goal of providing insight into their compatibility with clinical proteomics workflows. One method entailed the use of immobilized trypsin (SMART Digest Trypsin) with RapiGest SF, an acid-labile surfactant designed to enhance the in-solution enzymatic digestion of proteins. The other method incorporated a commercially available sample preparation kit, iST-BCT, which contains standardized reagents. Significantly higher protein sequence coverage, albeit with lower digestion efficiency, was obtained with the immobilized trypsin + RapiGest SF workflow, whereas the iST-BCT workflow was quicker and had marginally better reproducibility. Protein relative abundance analysis revealed that the serum proteomes clustered primarily by the sample processing workflow and secondarily by disease state. We conducted a time course study to determine whether differences in the relative abundance of diagnostic high-grade serous ovarian cancer serum protein biomarker candidates were biased according to the duration of enzymatic digestion. Our results highlight the importance of optimizing enzymatic digestion kinetics according to the peptide targets of interest while considering the sensitivity of the downstream analytical method utilized in clinical proteomics workflows designed to measure biomarkers.

High-abundance serum glycoproteins as valuable resources for glycopeptide standards

High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these high-abundance glycoproteins (HAGPs) can be used as valuable standard glycopeptide resources, as long as the structural features of their glycans have been well defined at the glycosite-specific level. By directly analyzing intact glycopeptides enriched from serum, we identified 1322 unique glycopeptides at 48 N-glycosites from the top 12 HAGPs (19 subclasses). These HAGPs could be further classified into four major groups based on the structural features of their attached N-glycans. Immunoglobins including IGHG1/2/3/4, IGHA1/2 and IGHM were mostly modified by core fucosylated and bisected N-glycans with rarely sialic acids. Alpha-1-acid glycoproteins (ORM1/2) and haptoglobins (HP) were mainly modified by tri-and tetra-antennary (40 %) N-glycans with antenna-fucoses and sialic acids. Complement components C3 and C4A/B were highly modified by oligo-mannose glycans. The other HAGPs including SERPINA1, A2M, TF, FGB/G and APOB mainly contain bi-antennary complex glycans with the common core structure and (sialyl-) LacNAc branch structures. These HAGPs are easily detected by LC-MS analysis and therefore could be used as standard glycopeptides for glycoproteomic methodology studies as well as possible clinical utilities.

Interleukin-9 promotes EMT-mediated PM2.5-induced pulmonary fibrosis by activating the STAT3 pathway.

This study investigated the impact of PM2.5 on promoting EMT in PM2.5-induced pulmonary fibrosis (PF) development and explored molecular mechanisms of the IL-9/STAT3/Snail/TWIST1 signaling pathway in PF owing to PM2.5. Four groups of male SD rats were formed: control (0mg/kg.bw), low (1mg/kg.bw), medium (5mg/kg.bw), and high-dose (25mg/kg.bw) PM2.5 groups. Experimental rats were subjected to PM2.5 exposure via intratracheal instillation, given once weekly for 16weeks. 24 h after the final exposure, blood, BALF, and lung tissues were collected. Pulmonary epithelial cells underwent cultivation and exposure to varying PM2.5 concentrations with/without inhibitors for 24h, after which total protein was extracted for relevant protein assays. The findings demonstrated that PM2.5 damaged lung tissue to different degrees and led to PF in rats. Rats subjected to PM2.5 exposure exhibited elevated concentrations of IL-9 protein in both serum and BALF, and elevated levels of IL-9 and its receptor, IL-9R, in lung tissues, compared to control counterparts. Furthermore, PM2.5-exposed groups demonstrated significantly augmented protein levels of p-STAT3, Snail, TWIST1, Vimentin, COL-I, and α-SMA, while displaying notably diminished levels of E-Cadherin compared to control group. The same findings were observed in PM2.5-treated cells. In BEAS-2B cells co-treated with Stattic (STAT3 inhibitor) and PM2.5, the opposite results occurred. Similar results were obtained for cells co-treated with IL-9-neutralizing antibody and PM2.5. Our findings suggest PM2.5 mediates PF development by promoting IL-9 expression, leading to STAT3 phosphorylation and upregulation of Snail and TWIST1 expression, triggering EMT occurrence and progression in lung epithelial cells.

A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB).

Serum Proteomic Predictors of Calcification of Solitary Cysticercus Granuloma.

Solitary cysticercus granulomas (SCG), prevalent among Indian patients with new-onset seizures, either resolve completely or transform into calcified granulomas. This study aimed to identify serum proteins through liquid chromatography-tandem mass spectrometry that could predict calcification of SCGs in 20 patients with SCG with at least 6-months of follow-up. At a median follow-up of 14 months, the SCG had calcified (n = 5), resolved (n = 11), or persisted (n = 4). Two serum proteins, ECM1 and MST1, were present in significantly higher serum concentrations, and AZGP1 in significantly lower concentration in subjects with calcifying SCGs than in those with lesions that resolved or persisted. On multivariate analysis, only ECM1 (odds ratio: 1.7, 95% CI: 0-2.8) and MST1 (odds ratio: 3.3, 95% CI: 0-4.1) were independent predictors of calcification of SCG. Combining elevated levels of serum ECM1 and MST1 had a sensitivity of 100% and specificity of 100% in differentiating granulomas that calcified from those that resolved/persisted. Increased expression of serum ECM1 and MST1 in patients with SCG might predict calcification.

Bioaccumulation of Deltamethrin and Piperonyl butoxide in Labeo rohita fish

Deltamethrin (DLM), in combination with the synergist piperonyl butoxide (PBO), is extensively used in pest control programs due to its potent pesticidal properties and appreciable safety margin. However, various research studies report their adverse effects on non-target organisms. In this study, we investigated the toxicity of DLM, PBO, and a DLM-PBO (3:1) combination on Labeo rohita (L. rohita) fish fingerlings. Fish behavior and mortality rates were recorded at different time intervals up to 96 h for concentrations of 0.003, 0.007, 0.015, 0.031, and 0.062 µg/mL, respectively. Biochemical, hematological, and histopathological studies were carried out. High-performance liquid chromatography (HPLC) was used to detect and quantify residues in fish samples. The LC50 values after 48 h for DLM, PBO, and DLM-PBO exposed fish fingerlings were found to be 0.028, 0.066, and 0.007 µg/mL, respectively. At a concentration of 0.003 µg/mL of DLM, PBO, and DLM-PBO, the treated fish fingerlings exhibited similar behavior to the control group. Hematological parameters, such as red blood cell (RBC) and white blood cell (WBC) counts, were reduced in the treated groups compared to the control. Biochemical parameters showed increased levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), while total serum protein levels decreased in DLM, PBO, and DLM-PBO treated fingerlings. Histopathological examination of liver, gill, and heart tissues revealed lesions with hydropic degeneration in the liver and fusions of gill lamellae in the treated tissues. Fish fingerlings exposed to the DLM-PBO combination appeared highly prone to toxicity compared to those treated with DLM and PBO separately.

Anthropometric and Nutritional status of Chronic Obstructive Pulmonary Disease presenting in Acute Exacerbation in Tertiary care Hospital in Eastern Nepal

Background: There is scarcity of data regarding the nutritional status of COPD patients presenting in exacerbation in our setup, thus this observational study was conducted. Methods: We performed an observational study of patients with acute exacerbation of COPD, who were admitted in the Department of Pulmonary, Critical care and Sleep Medicine in tertiary hospital in eastern Nepal from April 2023 to June 2023. Results: During the study period, a total of 154 patients of COPD with exacerbations were admitted in our department. The baseline anthropometric parameters, lab parameters as well as the malnutrition scores were determined. The mean BMI was 21.82 ± 3.92 kg/m2 and only 29% had BMI < 18.5 kg/m2.The mean hemoglobin, mean cell volume, serum protein, serum albumin, serum calcium, phosphorus and vitamin D level were 12.43 ± 2.32 g/dL, 84.4 ± 9.41 fL, 6.42 ± 1.74 g/ dL, 3.32 ± 0.34 g/dL, 8.98 ± 0.63 mg/dL, 3.02 ± 0.42 mg/dL, 18.48 ± 8.22 pg/mL and 40%, 12%, 28%, 41%, 31%, 42% and 49% of these values were below the lower normal limit respectively. The nutritional status tool used NRS-2002, MUST and MNAS-F screened malnutrition in about 68%, 51% and 54% respectively. There shows a discrepancy between the evaluation of the malnutrition assessed by BMI with that of nutritional assessment score. Conclusion: COPD who present in exacerbations are malnourished, but use of sole BMI to rule out malnutrition in such group of patients can cause false negative result.

Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia

Abstract: BACKGROUND: Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited. OBJECTIVES: The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls. PATIENTS MATERIALS AND METHODS: This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded. RESULTS: Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls. CONCLUSIONS: Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

The Impact of ARMS2 (rs10490924), VEGFA (rs3024997), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), and IL1B1 (rs1143623) Polymorphisms and Serum Levels on Age-Related Macular Degeneration Development and Therapeutic Responses.

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Anti-vascular endothelial growth factor (anti-VEGF) therapies are effective but do not respond optimally in all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the ARMS2 (rs10490924), IL1B1 (rs1143623), TNFRSF1B (rs1061622), TNFRSF1A (rs4149576), VEGFA (rs3024997), ARMS2, IL1B1, TNFRSF1B, TNFRSF1A, and VEGFA serum levels in AMD development and treatment efficacy. This study examined the associations of specific genetic polymorphisms and serum protein levels with exudative and early AMD and the response to anti-VEGF treatment. The AA genotype of VEGFA (rs3024997) was significantly associated with a 20-fold reduction in the odds of exudative AMD compared to the GG + GA genotypes. Conversely, the TT genotype of ARMS2 (rs10490924) was linked to a 4.2-fold increase in the odds of exudative AMD compared to GG + GT genotypes. In females, each T allele of ARMS2 increased the odds by 2.3-fold, while in males, the TT genotype was associated with a 5-fold increase. Lower serum IL1B levels were observed in the exudative AMD group compared to the controls. Early AMD patients had higher serum TNFRSF1B levels than controls, particularly those with the GG genotype of TNFRSF1B rs1061622. Exudative AMD patients with the CC genotype of TNFRSF1A rs4149576 had lower serum TNFRSF1A levels compared to the controls. Visual acuity (VA) analysis showed that non-responders had better baseline VA than responders but experienced decreased VA after treatment, whereas responders showed improvement. Central retinal thickness (CRT) reduced significantly in responders after treatment and was lower in responders compared to non-responders after treatment. The T allele of TNFRSF1B rs1061622 was associated with a better response to anti-VEGF treatment under both dominant and additive genetic models. These findings highlight significant genetic and biochemical markers associated with AMD and treatment response. This study found that the VEGFA rs3024997 AA genotype reduces the odds of exudative AMD, while the ARMS2 rs10490924 TT genotype increases it. Lower serum IL1B levels and variations in TNFRSF1B and TNFRSF1A levels were linked to AMD. The TNFRSF1B rs1061622 T allele was associated with better anti-VEGF treatment response. These markers could potentially guide risk assessment and personalized treatment for AMD.

In Vitro Spectroscopic Investigation of Losartan and Glipizide Competitive Binding to Glycated Albumin: A Comparative Study.

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSAGLC, gHSAFRC) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicated that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSAGLC and gHSAFRC, compared to HSA, resulting in less stable drug-protein complexes. The study revealed that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand-albumin) and ternary systems (ligand-albumin-ligandconst) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS-albumin complex or LOS in the GLP-albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs, to ensure optimal therapeutic efficacy and safety.