Serum Samples Research Articles

The Preventive Effect of Zinc Sulfate against Olanzapine-Induced Testicular Toxicity in Male Rats.

Male infertility is a complex and multifactorial clinical condition affecting a large population attributed to several factors, including perturbation in oxidative stress and the level of essential trace elements. Oxidative stress exerts multiple issues related to reproductive health, including male infertility, decreased sperm motility, sperm DNA damage, and an increased susceptibility to genetic disorders. Besides chemical toxins and food allergens in junk food items, many drugs can also lead to male infertility. Olanzapine (OLZ), a general antipsychotic drug, has also been reported to induce male fertility. A great deal of literature entails that supplementation of zinc can alleviate oxidative stress-related clinical complications, including male infertility. This study investigates the potential protective effects of zinc sulfate (ZnSO4) on OLZ-induced male infertility. In the present study, there were four treatment groups (n = 6): group 1 as control (without any treatment); group 2 treated with OLZ (10mg/kg) orally daily for 6weeks; groups 3 and 4 treated with 50mg/kg and 100mg/kg of ZnSO4 respectively in pre-exposed OLZ (10mg/kg) orally daily for 6weeks. After completion of the treatment, the biochemical analysis of serum and tissue samples demonstrated that group 2 had compromised levels of antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)) as well as elevated levels of stress parameters (oxidized glutathione (GSSG), malondialdehyde (MDA), and nitric oxide (NO)) as compared to the control by a significant extent (p ≤ 0.05). However, supplementation of ZnSO4 significantly corrected all these parameters in a dose-dependent way in groups 3 and 4 (p ≤ 0.05). Other health indicators, like taurine, enzyme Q10, phosphatidylcholine, ascorbic acid, and vitamin E, were also observed to improve prominently with the supplementation of ZnSO4. Intriguingly, all the fertility parameters (sperm motility, count and level of testosterone) were also found to be significantly enhanced with decreased sperm abnormalities in both the combination groups. The histological evaluation of the testis section also agreed with the biochemical analysis in this investigation. Therefore, the study strongly advocates that supplementation of Zn can ameliorate OLZ-induced male infertility to a significant extent.

Increasing the dual-enzyme cascade biocatalysis efficiency and stability of metal-organic frameworks via one-step coimmobilization for visual detection of glucose.

In biosensing analysis, the activity of enzyme systems is limited by their fragility, and substrates catalyzed by monoenzymes tend to undergo spontaneous decomposition during ineffective mass transfer processes. In this study, we propose a novel strategy to encapsulate the glucose oxidase and horseradish peroxidase (GOx&HRP) cascade catalytic system within the hydrophilic zeolite imidazole framework ZIF-90. By leveraging the specific pore structure of ZIF-90, we effectively immobilized GOx and HRP molecules in their three-dimensional conformations, which improved the catalytic activity of the encapsulated enzymes compared with that of free GOx and HRP in various harsh environments. Additionally, our strategy reduced the occurrence of ineffective mass transfer and enhanced the sensitivity of the biosensor through an enzyme cascade system. When this biosensor was applied to serum samples containing complex biological matrices, the degradation of GOx&HRP by various proteases and the surface adsorption of diverse biomolecules were effectively prevented, thereby generating stable and reliable signals of glucose levels. The sensor shows remarkable sensitivity and selectivity for determining glucose concentrations ranging from 0 to 2.5 μg ml-1, with a detection limit as low as 0.034 μg ml-1. Furthermore, we developed a paper-based colorimetric sensor utilizing GOx&HRP@ZIF-90 integrated with a smartphone platform for the visual detection of blood glucose.

Subtyping strokes using blood-based protein biomarkers: A high-throughput proteomics and machine learning approach.

Rapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high-throughput proteomics. We collected serum samples within 24 h from acute stroke (IS & ICH) and mimics patients. In the discovery phase, SWATH-MS proteomics identified differentially expressed proteins, which were validated using targeted proteomics in the validation phase. We conducted interaction network and pathway analyses using Cytoscape 3.10.0. We determined cut-off points using the Youden Index. We developed three prediction models using multivariable logistic regression analyses. We assessed the model performance using statistical tests. We included 20 IS and 20 ICH in the discovery phase and 150 IS, 150 ICH, and six stroke mimics in the validation phase. We quantified 375 proteins using SWATH-MS. Between IS and ICH, we discovered 20 differentially expressed proteins. In the validation phase, the combined prediction model including three biomarkers: GFAP (aOR 0.04; 95%CI .02-.11), MMP-9 (aOR .09; .03-.28), APO-C1 (aOR 5.76; 2.66-12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, negative predictive value: 94%). Adding biomarkers to clinical variables improved discrimination by 26% (p < .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics. Our study demonstrated that GFAP, MMP-9 and APO-C1 biomarkers independently differentiated IS from ICH within 24 h and significantly improved the discrimination ability of prediction models. Temporal profiling of these biomarkers in the acute phase of stroke is warranted.

Combined bisoprolol and trimetazidine ameliorate arsenic trioxide -induced acute myocardial injury in rats: targeting PI3K/GSK-3β/Nrf2/HO-1 and NF-κB/iNOS signaling pathways, inflammatory mediators and apoptosis

Background Arsenic-trioxide (ATO) is an effective therapy for acute promyelocytic leukemia. Unfortunately, its utility is hindered by the risk of myocardial injury. Both bisoprolol (BIS) and trimetazidine (TMZ) have various pharmacological features, including anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Aim The cardioprotective effects of BIS and TMZ were studied, and their mechanistic role in ameliorating ATO-induced myocardial injury. Materials and Methods Forty male Wistar rats were randomly allotted into five groups as follows: normal control group (received normal saline, orally), ATO group (7.5 mg/kg, orally), BIS (8 mg/kg, orally), TMZ (60 mg/kg, orally), and finally combination group (BIS+TMZ+ATO). Following 21 days, samples of serum and cardiac tissues were obtained to perform biochemical, molecular, and histopathological investigations. Results The present study showed that ATO caused myocardial injury evidenced by changes in serum biomarkers (Aspatate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase-MB, and cardiac troponin-1), electrolyte imbalance, and lipid profiles alongside histopathologic changes. In addition, ATO administration significantly elevated malondialdehyde, nicotinamide adenine dinucleotide phosphate hydrogen oxidase, myloperoxidase, total nitrite, inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1β, interleukin-6, 8-Hydroxy-2’-deoxyguanosine, nuclear factor NF-kappa-B p65 subunit, glycogen synthase kinase-3 beta, and caspase-3 expression contemporaneously with down-regulation of reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, heme oxygenase 1, nuclear factor erythroid 2–related factor 2, phosphatidylinositol-3 kinase, p-PI3K, and Bcl-2 expression. Interestingly, pretreatment with BIS and TMZ significantly reversed the detrimental effects of ATO-induced myocardial injury at both cellular and molecular levels. Otherwise, combining the two drugs displayed more enhancement than each drug alone. Conclusion The present research depicted that BIS and TMZ have the potential to protect the heart and provide therapeutic benefits by preventing acute heart injury induced by ATO. This is achieved by reversing the redox-sensitive pathway, reducing inflammation, and inhibiting apoptosis.

Alternative Day Fasting protocol Attenuates High Fructose-Induced Activation of the TGF-beta/Smad Signaling Pathway

Purpose: This study aims to explore the protective effects of alternate-day fasting (ADF) against metabolic disturbances induced by high fructose (HF) intake, with a particular focus on modulating the transforming growth factor-beta1 (TGF-β1) / mother against decapentaplegic homolog 2 (Smad2) signaling pathway. Materials and Methods: Four groups of rats (n=7 per group) were included: Control, ADF, HF (20% fructose in drinking water), and HF+ADF. The ADF protocol was applied with 24 hours of ad libitum feeding followed by 24 hours of fasting over a 5-week period. After five weeks, body weight (BW), muscle, and fat mass were measured. Serum samples were analyzed using ELISA to assess levels of TGF-β1, Smad2, connective tissue growth factor (CTGF), and total oxidant-antioxidant status (TOS-TAS). Results: Results indicated that that HF significantly increased final BW, and ADF reduced this weight gain (p=0.001). ADF also led to lower gastrocnemius-soleus muscle weights compared to controls (p=0.001), but mitigated fructose-induced retroperitoneal fat accumulation. TAS levels were higher, and TOS levels were lower in the ADF groups, showing an antioxidant shift (p

An Evaluation of the Cellular and Humoral Response of a Multi-Epitope Vaccine Candidate Against COVID-19 with Different Alum Adjuvants

SARS-CoV-2 (Betacoronavirus pandemicum) is responsible for the disease identified by the World Health Organization (WHO) as COVID-19. We designed “CHIVAX 2.1”, a multi-epitope vaccine, containing ten immunogenic peptides with conserved B-cell and T-cell epitopes in the receceptor binding domain (RBD) sequences of different SARS-CoV-2 variants of concern (VoCs). We evaluated the immune response of mice immunized with 20 or 60 µg of the chimeric protein with two different alum adjuvants (Alhydrogel® and Adju-Phos®), plus PHAD®, in a two-immunization regimen (0 and 21 days). Serum samples were collected on days 0, 21, 31, and 72 post first immunization, with antibody titers determined by indirect ELISA, while lymphoproliferation assays and cytokine production were evaluated by flow cytometry. The presence of neutralizing antibodies was assessed by surrogate neutralization assays. Higher titers of total IgG, IgG1, and IgG2a antibodies, as well as increased proliferation rates of specific CD4+ and CD8+ T cells, were observed in mice immunized with 60 μg of protein plus Adju-Phos®/PHAD®. This formulation also generated the highest levels of TNF-α and IFN-γ, in addition to the presence of neutralizing antibodies against Delta and Omicron VoC. These findings indicate the potential of this chimeric multi-epitope vaccine with combined adjuvants as a promising platform against viral infections, eliciting a TH1 or TH1:TH2 balanced cell response.

Exploratory study on reference intervals of calprotectin and pentraxin 3.

The aim of our study was to determine reference intervals for serum pentraxin 3 and calprotectin, as well as for urine calprotectin according to the CLSI EP28-A3C guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory. A total of 120 serum and urine samples from either healthy volunteers or outpatients were used for reference interval establishment. The participants had CRP levels, leucocyte counts, serum urea levels, creatinine levels, and estimated glomerular filtration rates (CKD-EPI eGFRs) within the reference range and no medical history of acute/chronic inflammatory diseases/conditions or cancer. Calprotectin was measured via a commercially available turbidimetric method - the Bühhlmann fCAL® Turbo Reagent Kit - while pentraxin 3 was measured using the Human Pentraxin 3 ELISA Kit from the BioVendor Group. The serum calprotectin reference range was ≤3.6mg/L, the 90% CI for the upper reference range was 3.1-4.1mg/L, while the serum pentraxin 3 reference concentration was ≤3.0µg/L, and the 90% CI for the upper reference range being 2.7-3.2µg/L. Additionally, the urinary calprotectin concentration was ≤1.4mg/L, with a 90% CI for the upper reference range of 1.0-1.7mg/L. This study reports sample and method-specific reference intervals for the detection of various inflammatory conditions.

Serum amikacin concentrations in dogs with naturally occurring open wounds treated with topical amikacin in carboxymethylcellulose hydrogel.

To quantify serum amikacin concentrations in dogs undergoing wound management with topical amikacin (45 mg/mL) 3% carboxymethylcellulose hydrogel. Prospective clinical study. Eleven client-owned dogs. Dogs with naturally occurring wounds, undergoing treatment with topical amikacin gel, were enrolled. A whole blood sample was collected prior to initial application of the gel. Up to a maximum dose of 30 mg/kg of gel, was applied directly on the wound and the wound was bandaged. Serial blood sampling was performed at approximately 2, 4, 8, 12, 18, 24, 32, 40, 48, 56, 64, and 72 h after application of amikacin gel. The sampling schedule was reset following each bandage change and new application of the gel. Up to 20 samples per dog were collected. The Siemens Syva EMIT Amikacin Assay was used to quantify the concentration of amikacin in each blood serum sample. The lower limit of quantification (LLOQ) of the test was 2.5 μg/mL. Amikacin gel was applied a total of 31 times (dose range, 0.1-24.9 mg/kg). A total of 153 samples were analyzed. Five samples in three different dogs were above the LLOQ at approximately 2 h after gel application (range 2.75-3.82 μg/mL). All other samples were below the LLOQ. Routine use of amikacin gel for open wound management did not result in serum amikacin levels above 5 μg/mL. Topical amikacin gel may be a safe treatment option for wounds in dogs with resistant infections or biofilms.

Integration of Immunosyringe Sensors with Bar-Chart Chips for Prick-and-Read Testing of Prostate Specific Antigen.

Pressure-based signal transduction is of promise in developing microfluidic immunoassays such as volumetric bar-chart chips (V-chips), but new working principles are required to further simplify the methods in point-of-care testing (POCT). Herein, we developed immunosyringe sensors and integrated them with bar-chart chips for simple prick-and-read testing of prostate specific antigen (PSA) as a model target. Disposable syringes served as the host for the construction of the sandwich-type immuno-recognition system. Platinum nanoparticles (Pt NPs) as the peroxidase-mimicking detection probe catalyzed the decomposition of H2O2 to produce O2 in the syringe cylinders, enabling the pressure-driven automatic injection of liquids from the syringes. The immuno-recognition event in the syringes was thereby converted into the quantitative autoinjection behavior of the syringes, namely, immunosyringe sensors. By simply pricking the sensors to bar-chart chips, we visually and quantitatively read the immunoassay signals as the bar-chart injection distance of liquids from the syringes in channels of the chips. The immunoassay showed a limit of detection (LOD) of 0.41 ng/mL in PSA detection with satisfactory accuracy in testing clinical serum samples. Owing to the integration with the immunosyringe sensors, this method, in comparison with conventional V-chips, works in a simpler prick-and-read manner without complex chip configurations and specialized chip operations (e.g., on-chip loading of microvolume reagents and sealing treatments). Therefore, the immunoassay shows great potential in POCT applications.

IgE sensitization profiles to food, inhalant and insect venom in Norwegian blood donors and their impact on blood transfusions.

Allergen-specific immunoglobulin-E (As-IgE) in blood donors (BD) can be transferred to transfusion recipients via plasma-containing blood components (PCBC) and sensitize recipient's mast cells. These cells can activate upon allergen exposure and cause allergy. This study aimed to assess sensitization profiles against an array of allergens in BD to identify donors with As-IgE and explore if this IgE can lead to allergic symptoms in recipients. Furthermore IgE sensitization was characterized in donors of PCBC that were associated with allergic transfusion reactions (ATR) in recipients. Serum samples from 300 randomly selected BD (RSBD) and 40 BD selected following 26 ATRs in patients transfused with PCBC from these donors were collected. IgE sensitization was tested by a line-blot enzyme-immunoassay and an ELISA-based IgE multiplex assay. Thirty-eight per cent of the RSBD had IgE to one or several allergens. High IgE levels with a potential to transfer to recipients of PCBC were also detected in some BD. Investigation of 2/3 of the PCBC from sensitized RSBD revealed no reports of ATR in recipients. IgE testing of donors associated with an ATR showed sensitization in 65% of the cases. We conclude that IgE testing of BD can reveal sensitization to different allergens, even though persons with severe allergies are not accepted as BD. The sensitization frequency appears higher in BD of PCBC that led to an ATR compared to the RSBD. No reports on ATR were found for PCBC from sensitized RSBD. More studies are needed to address the role of IgE-sensitization of BD in ATR.

Point-of-Care Detection of Carcinoembryonic Antigen (CEA) Using a Smartphone-Based, Label-Free Electrochemical Immunosensor with Multilayer CuONPs/CNTs/GO on a Disposable Screen-Printed Electrode

In order to identify carcinoembryonic antigen (CEA) in serum samples, an innovative smartphone-based, label-free electrochemical immunosensor was created without the need for additional labels or markers. This technology presents a viable method for on-site cancer diagnostics. The novel smartphone-integrated, label-free immunosensing platform was constructed by nanostructured materials that utilize the layer-by-layer (LBL) assembly technique, allowing for meticulous control over the interface. Detection relies on direct interactions without extra tagging agents, where ordered graphene oxide (GO), carbon nanotubes (CNTs), and copper oxide nanoparticles (CuONPs) were sequentially deposited onto a screen-printed carbon electrode (SPCE), designated as CuONPs/CNTs/GO/SPCE. This significantly amplifies the electrochemical signal, allowing for the detection of low concentrations of target molecules of CEA. The LBL approach enables the precise construction of multi-layered structures on the sensor surface, enhancing their activity and optimizing the electrochemical performance for CEA detection. These nanostructured materials serve as efficient carriers to significantly increase the surface area, conductivity, and structural support for antibody loading, thus improving the sensitivity of detection. The detection of carcinoembryonic antigen (CEA) in this electrochemical immunosensing transducer is based on a decrease in the current response of the [Fe(CN)6]3−/4− redox probes, which occurs in proportion to the amount of the immunocomplex formed on the sensor surface. Under the optimized conditions, the immunosensor exhibited good detection of CEA with a linear range of 0.1–5.0 ng mL−1 and a low detection limit of 0.08 ng mL−1. This label-free detection approach, based on signal suppression due to immunocomplex formation, is highly sensitive and efficient for measuring CEA levels in serum samples, with higher recovery ranges of 101% to 112%, enabling early cancer diagnosis. The immunosensor was successfully applied to determine CEA in serum samples. This immunosensor has several advantages, including simple fabrication, portability, rapid analysis, high selectivity and sensitivity, and good reproducibility with long-term stability over 21 days. Therefore, it has the potential for point-of-care diagnosis of lung cancer.

Role of Milk Intake in Modulating Serum Lipid Profiles and Gut Metabolites

Background/Objectives: Milk is one of the main sources of nutrition in people’s daily diet, but the fat in milk raises health concerns in consumers. Here, we aimed to elucidate the impact of Buffalo milk and Holstein cow milk consumption on blood lipid health through metabolomics analysis. Methods: Golden hamsters were administered Murrah Buffalo milk (BM) or Holstein cow milk (HM), and the body weight and serum lipid indicators were tested and recorded. The hamsters receiving equal amounts of physiological saline were used as the negative control (NC). Serum and fecal samples were collected, and LC-MS was used to identify the metabolites in the samples. Results: The results showed that both the BM and HM groups exhibited a significant reduction in body weight compared to that of the NC group from day 9, and the serum TG, TC, and LDL-C levels were significantly lower than those of the NC group. Further analysis identified 564 and 567 metabolites in the serum and fecal samples shared in the BM and HM groups and significantly different from those in the NC group, which were mainly enriched in the pathways related to lipid metabolism, such as fatty acid biosynthesis, arachidonic acid metabolism, and primary bile acid biosynthesis. Correlation analysis further suggested that milk intake can increase the levels of Muramic Acid, Oleoyl Ethanolamide, Seratrodast, Chenodeoxycholic Acid, Docosahexaenoic Acid Ethyl Ester, and Deoxycholic Acid in the serum and gut microbiota, which may affect TG, TC, HDL-C, and LDL-C in the serum, and thereby benefit the body’s lipid health. Conclusions: The results further confirmed that milk intake has a beneficial effect on blood lipid health by altering multiple metabolites in the serum and the gut. This study provides novel evidence that milk consumption is beneficial to health and is a reference for guiding people to a healthy diet.

The first serological survey of C. Burnetii in domestic animals in Poland

Background• Q fever, known as coxiellosis in animals, represents a global zoonotic threat caused by the intracellular bacterium Coxiella burnetii (C. burnetii). The disease affects many animal species, including those considered significant reservoirs, such as cattle, sheep and goats. Transmission of the pathogen to other domestic animals, including companion animals, and then to humans has also been observed, highlighting the importance of understanding the epidemiology and prevalence of C. burnetii among companion animals. The present study aimed to determine the frequency of seroreagents for C. burnetii within pet dogs, cats and rabbits from urban Poland areas and identify possible risk factors for these animals.Results• In total, serum samples from 491 dogs, 427 cats and 93 rabbits were used in the study. The seroprevalence of anti-C. burnetii antibodies in dogs and cats reached 0.61% (3/491; 95% CI: 0.21–1.78) and 0.23% (1/427; 95% CI: 0.04–1.31), respectively. No significant differences in seroprevalence across species and different subpopulations (age group, gender, exhibited symptoms, or sampling location) were found. All 93 samples from rabbits were negative for anti-C.burnetii antibodies.Conclusions• The seroprevalence rates of C. burnetii in dogs and cats were low; however, our results confirm that pet dogs and cats in Poland can be exposed to C. burnetii and may exhibit serological reactions. It has been reported that people who come into contact with secretions and excretions from the reproductive systems of dogs and cats (such as breeders, veterinarians, and veterinary clinic staff) may be at risk of contracting C. burnetii. Based on the findings, it is advised to be particularly cautious, especially when assisting with dogs and cats giving birth. Coxiellosis should be considered a potential cause of reproductive disorders in these animals. The results indicate that rabbits are probably less important in the circulation of the C. burnetii in the present study. This is the first serological survey of C. burnetii in pet dogs, cats and rabbits in Poland.

Effect of Anion-Directed Structural Tuning of Triazole-Containing Ag(I) Coordination Polymers for "Turn-on" Sensing of the Disulfide (-S-S-) Amino Acid over the Monosulfide (-SH) Form: Experiments and DFT Corroboration.

Identification of disulfide-peptide-bond-containing glutathione (GSSG) over the monosulfide form (GSH) remains a very challenging task because of their identical chemical properties. Although GSH detection has been well documented, selective detection of GSSG has rarely been reported. Here, four cationic Ag-based coordination polymers (Ag CPs) were synthesized using newly synthesized monotriazole linker 3-amino-5-(4H-1,2,4-triazol-4-yl)pyridine to selectively screen GSSG over GSH. The judicious choice of the counteranion in the metal salt changes the architecture, which affects the detection limit at the parts per million level. The restriction of the photoinduced electron transfer process is the driving reason for the enhancement of the fluorescence, owing to the favorable energy band gap match of the Ag CPs with GSSG over GSH. The de novo strategy for incorporating polar heteroatoms (N) into the CP network plays a pivotal role in the host-guest noncovalent interactions with donor-acceptor transfer of electrons, which was supported by X-ray photoelectron spectroscopy and density functional theory studies. The Ag CPs are thermochemically robust, recyclable, and work efficiently in a very short time (within ∼14-18 s) in different pH ranges. Additionally, detection of GSSG in serum samples was carried out with appreciable detection limits and recovery percentages (94.40-117.89%).

Association between NT-proBNP levels and risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies

Background and aimsN-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in clinical practice, particularly for heart failure, but its role in predicting atrial fibrillation (AF) risk is not fully...

A facile optical fiber-embedded microfluidic biochip for rapid and sensitive detection of microRNA-let-7a in serum.

Anovel hybridization chain reaction (HCR) powered optical fiber-embedded microfluidic biochip (HCR-FMB) has been constructed for ultrafast and sensitive detection of lethal-7a (let-7a) in serum. By integrating HCR, fluorescence energy resonant transfer, and evanescent wave fluorescence principle, the HCR-FMB enables detecting let-7a with satisfactory limit of detection of 100.0 pM within 6min at room temperature, and demonstrates excellent specificity. TheHCR-FMB can directly detect let-7a in serum with high sensitivity and without any pre-treatment, and good recoverieswere observed for let-7a in serum samples, demonstrating their potential application tothe analysis of serum samples. The HCR-FMB exhibits several advantages, including rapidity, enzyme-free, miniaturization, ease-of-operation, field-deployment applicability, minimal-equipment, and cost-effectiveness. The HCR-FMB can be considered arevolutionary detection device that rapidly adapts and deploys in various settings, especially in low medical resource regions.

Use of thymidine kinase 1 autoantibody, thymidine kinase antigen, extracellular protein kinase A autoantibody, and C-reactive protein for early detection of malignant tumors in dogs.

Although the importance of early diagnosis of malignant tumors is a major concern, an easily accessible in-house method has not been established. To investigate the most optimal model by combining thymidine kinase 1 (TK1) autoantibody, extracellular protein kinase A (ECPKA) autoantibody, TK1 antigen, C-reactive protein (CRP), age, breed, and sex. Serum samples from 1702 dogs were collected from local animal hospitals and referral animal medical centers in Korea. TK1 autoantibody, ECPKA autoantibody, and CRP were measured using LFIA methods in serum samples of dog to design a new neoplastic index (NI) for early detection of malignant tumors in dogs. AUC of TK1 autoantibody model with TK1 antigen, CRP, age, and breed in multiple logistic regression analysis was 0.966 (TK1 autoantibody, P = .0005; TK1 antigen, P = .0003), and when the cutoff value was 0.417, the specificity was 87.1%, and sensitivity was 96.4%. Regression coefficients were 24.4, 20.5, 24.8, 10.6, respectively in TK1 autoantibody, TK1 antigen, CRP, and age, and the effect by breed (regression coefficient 2.1, 3.0) was the lowest. The same multiple logistic regression analysis on dogs with lymphoma, and AUC of TK1 autoantibody model was 0.981 (all P < .0001, TK1 antigen P = .09), when the cutoff value was 0.352, the specificity was 92.9%, and sensitivity was 93.7%. The NI including TK1 autoantibody could be useful in the screening test for both lymphoma and other tumors.

Herd and animal level seroprevalence and associated risk factors of Leptospira interrogans sensu lato serovar Hardjo in cattle in southwest Ethiopia

Leptospirosis is a significant zoonotic disease that causes high economic losses in cattle production due to its association with abortions, stillbirths, infertility, and reduced milk yields. However, the epidemiology of bovine leptospirosis in Ethiopia is poorly understood. From October 2020 to October 2021, a cross-sectional study was conducted to investigate the seroprevalence of serovar Hardjo in cattle in southwest Ethiopia, as well as the associated risk factors. To test for the existence of L. Hardjo antibodies, blood samples were taken from 461 cattle. Indirect ELISA was used to identify the presence of antibodies against L. Hardjo in sera samples. We conducted a multivariable random-effect logistic regression analysis to identify potential risk factors associated with L. Hardjo seropositivity. An overall L. Hardjo seroprevalence of 24.7% (95% CI: 20.2–48.8) and 53.5% (95% CI: 45.7–90.5) was recorded at the animal level and the herd level, respectively, in the study areas. This study revealed six factors influencing L. Hardjo seropositivity in cattle herds. Large herds had twice the odds of seropositivity (OR = 2.0, 95% CI: 1.1–3.8) compared to small herds. Co-grazing cattle exhibited higher odds (OR = 2.2, 95% CI: 1.2–4.1) of seropositivity. Extensive management systems significantly increased the odds (OR = 10.3, 95% CI: 1.7–61.8) compared to semi-intensive systems. Highland cattle had higher odds (OR = 3.7, 95% CI: 1.4–10.3) than lowland cattle. Older cattle (OR = 4.6, 95% CI: 2.4–8.9) were more likely to be seropositive. At the herd level, extensive management (OR = 2.8, 95% CI: 1.3–5.8) and large herds (OR = 2.5, 95% CI: 1.3–4.7) increased the risk of seropositivity. Herds with sheep/goats (OR = 2.3, 95% CI: 1.3–4.1) were also at higher risk, highlighting significant L. Hardjo seropositivity risk factors in cattle herds. The study findings showed that leptospirosis was highly prevalent across the study areas. As a result, use proper management, raise zoonotic awareness for leptospirosis, and conduct molecular bovine leptospirosis research in study areas were recommended.

Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.

With the emergence of the precision medicine era, targeting specific proteins has emerged as a pivotal breakthrough in tumor diagnosis and treatment. Apurinic/apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays a crucial role in DNA repair and cellular redox regulation. This article comprehensively explores the fundamental mechanisms of APE1 as a multifunctional enzyme in biology, with particular emphasis on its potential significance in disease diagnosis and strategies for tumor treatment. Firstly, this article meticulously analyzes the intricate biological functions of APE1 at a molecular level, establishing a solid theoretical foundation for subsequent research endeavors. In terms of diagnostic applications, the presence of APE1 can be detected in patient serum samples, biopsy tissues, and through cellular in situ testing. The precise detection methods enable changes in APE1 levels to serve as reliable biomarkers for predicting tumor occurrence, progression, and patient prognosis. Moreover, this article focuses on elucidating the potential role of APE1 in tumor treatment by exploring various inhibitors, including nucleic acid-based inhibitors and small molecule drug inhibitors categories, and revealing their unique advantages in disrupting DNA repair function and modulating oxidative-reduction activity. Finally, the article provides an outlook on future research directions for APE1 while acknowledging major technical difficulties and clinical challenges that need to be overcome despite its immense potential as a target for tumor therapy.

Early Diagnosis of Bloodstream Infections Using Serum Metabolomic Analysis

Background: Bloodstream infections (BSIs) pose a great challenge to treating patients, especially those with underlying diseases, such as immunodeficiency diseases. Early diagnosis helps to direct precise empirical antibiotic administration and proper clinical management. This study carried out a serum metabolomic analysis using blood specimens sampled from patients with a suspected infection whose routine culture results were later demonstrated to be positive. Methods: A liquid chromatograph-mass spectrometry-based metabolomic analysis was carried out to profile the BSI serum samples. The serum metabolomics data could be used to successfully differentiate BSIs from non-BSIs. Results: The major classes of the isolated pathogens (e.g., Gram-positive and Gram-negative bacteria) could be differentiated using our optimized statistical algorithms. In addition, by using different machine-learning algorithms, the isolated pathogens could also be classified at the species levels (e.g., Escherichia coli and Klebsiella pneumoniae) or according to their specific antibiotic-resistant phenotypes (e.g., extended-spectrum β-lactamase-producing and non-producing phenotypes) if needed. Conclusions: This study provides an early diagnosis method that could be an alternative to the traditional time-consuming culture process to identify BSIs. Moreover, this metabolomics strategy was less affected by several risk factors (e.g., antibiotics administration) that could produce false culture results.