Serum Samples Research Articles

Molecular detection and genotyping of HBV from HBsAg positive patients in a tertiary hospital in Nigeria.

Nigeria remains one of the countries with a high hepatitis B virus (HBV) burden in Africa. Reports have indicated the presence of mixed HBV genotypes in Nigeria; however, there is still paucity of data regarding mixed genotype infections particularly in the Southern part of the country. Our aim is to determine the HBV genotype distribution among HBsAg-positive gastroenterology patients at the University College Hospital Ibadan, Nigeria. Serum samples were screened for HBsAg by ELISA, and positive samples were genotyped by semi-nested multiplex PCR for HBV genotypes A, B, C, D, E and F. Data generated were analyzed in R-studio. A total of 81/90 (90%) of HBsAg-positive samples were successfully genotyped, and genotype A was most prevalent with 15.7%, while genotypes B and E were the least with 1.2% each. Genotypes A/C infection was the highest among mixed infections with 40% prevalence, while genotypes A/D were the least prevalent mixed infection with 4.8%. We advocate for a comprehensive genotype analysis in larger cohorts across Nigeria, to give a more comprehensive understanding of the distribution and prevalence of different HBV genotypes population wide.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

Adjuvant therapy with zinc supplementation; anti-inflammatory and anti-oxidative role in multiple myeloma patients receiving autologous hematopoietic stem cell transplantation: a randomized controlled clinical trial.

Multiple myeloma (MM) patients are often accompanied by heightened levels of oxidative stress, even following bone marrow transplantation. Trace mineral supplements have been found to regulate and inhibit the activity of oxidative radicals and inflammatory factors, which are involved in the pathogenesis of MM. The study sought to evaluate the effectiveness of the supplementation by analyzing changes in oxidative, anti-oxidative, and inflammation markers. Patients were randomly assigned to a zinc or placebo group, with the former receiving 30mg of zinc or placebo tablets daily for 1month. Blood samples were collected from the patients on the day of transplantation, 15days, and 30days post-transplantation. Real-time PCR was employed to measure the expression of oxidative/antioxidative genes. Furthermore, the protein level of oxidative markers in serum samples was assessed. Finally, serum TNF-α concentrations were measured using the ELISA technique. The expression levels of SOD1, SOD2, and NRF2 genes were significantly higher on days 15 and 30 compared to the control group (P < 0.05), with a greater increase on day 30 (P < 0.05). Conversely, the expression levels of Keap1 and NOX2 genes were lower on day 30 than those of the control group (P < 0.05), with a further decrease from day 15 to day 30 (P < 0.05). The experimental group exhibited a notable reduction in TNF-α cytokine levels on day 30 compared to the control and placebo groups (P < 0.05). All findings were coordinated according to the nutritional questionnaire. Our findings suggest a potential benefit of zinc supplementation in managing the adverse effects of chemotherapy in MM patients, warranting further investigation.

Candidate Biomarkers For Response To Treatment In Psoriatic Disease.

To determine whether biologic therapy alters serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in psoriatic arthritis (PsA) and psoriasis (PsC) patients, and whether baseline levels of these proteins predict response to treatment for PsA. We included PsA patients on TNF inhibitors (TNFi), Interleukin-17 inhibitors (IL-17i), methotrexate (MTX), and untreated with bDMARDs or csDMARDs (untreated) and PsC patients on bDMARDs and matched untreated. Serum samples at baseline and 3-6 months follow-up were retrieved from the biobank. Protein levels were quantified using a Luminex multiplex assay. We compared follow-up vs baseline protein levels within groups and change in levels between groups. For the predictive potential of the biomarkers, we developed logistic regression classification models. Response to treatment was defined as: 1. Achieving low disease activity or remission (according to DAPSA), 2. 75% reduction in PASI, and 3. 50% reduction in actively inflamed joint count. In PsA, TNFi reduced serum levels of all five proteins, IL-17i increased ACP5 and CCL2, and MTX reduced MMP3. Changes in MMP3 and S100A8 levels were significantly different between untreated PsA and matched biologic-treated PsA (p<0.05). There were no significant differences between treated or untreated PsC patients. Baseline levels of CXCL10, MMP3, S100A8, and ACP5 had good predictive value (AUC>0.8) for response to biologics in PsA patients. Biologics treatment and MTX affect serum CXCL10, MMP3, S100A8, ACP5, and CCL2 levels in PsA patients. MMP3, S100A8, ACP5, and CXCL10 have potential use as serum biomarkers to predict response to treatment for PsA.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Metabolic Choreography of Energy Substrates During DCD Heart Perfusion.

The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking. Metabolites were analyzed using 1-dimensional 1H and 2-dimensional 13C-1H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways. Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate. Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.

Fabrication of rGO-decorated hBNNS hybrid nanocomposite via organic-inorganic interfacial chemistry for enhanced electrocatalytic detection of carcinoembryonic antigen.

Organic-inorganic hybrid nanocomposites (OIHN), with tailored surface chemistry, offer ultra-sensitive architecture capable of detecting ultra-low concentrations of target analytes with precision. In the present work, a novel nano-biosensor was fabricated, acquainting dynamic synergy of reduced graphene oxide (rGO) decorated hexagonal boron nitride nanosheets (hBNNS) for detection of carcinoembryonic antigen (CEA). Extensive spectroscopic and microscopic analyses confirmed the successful hydrothermal synthesis of cross-linked rGO-hBNNS nanocomposite. Uniform micro-electrodes of rGO-hBNNS onto pre-hydrolyzed ITO were obtained via electrophoretic deposition (EPD) technique at low DC potential (15V). Optimization of antibody incubation time, pH of supporting electrolyte, and immunoelectrode preparation was thoroughly investigated to enhance nano-biosensing efficacy. rGO-modified hBNNS demonstrated 29% boost in electrochemical performance over bare hBNNS, signifying remarkable electro-catalytic activity of nano-biosensor. The presence of multifunctional groups on the interface facilitated stable crosslinking chemistry, increased immobilization density, and enabled site-specific anchoring of Anti-CEA, resulting in improved binding affinity. The nano-biosensor demonstrated a remarkably low limit of detection of 5.47pg/mL (R2 = 0.99963), indicating exceptional sensitivity and accuracy in detecting CEA concentrations from 0 to 50ng/mL. The clinical evaluation confirmed its exceptional shelf life, minimal cross-reactivity, and robust recovery rates in human serum samples, thereby unraveling the potential for early, highly sensitive, and reliable CEA detection.

Comparison of Serum Vitamins C, D, and E in Iraqi Colorectal Cancer Patients with and without Non-Alcoholic Fatty Liver Disease to Healthy Individuals

Abstract Depending on their protective properties against different cases of Colorectal Cancer (CRC), vitamins C, D, and E are the main focus of this research. CRC is one of the global public health concerns. 30 healthy individuals provided serum samples, whereas the group of CRC patients was divided into three, totaling 90 individuals. Group I consisted of 30 newly diagnosed cases of CRC. Group II 30 consisted of consisted of 30 CRC patients who were administered three cycles of chemotherapy. Group III consisted of 30 diagnosed CRC patients who also have non-alcoholic fatty liver disease (NAFLD). The concentrations and groups of vitamins C, D, and E were evaluated using ELISA. The levels of Vitamin C were significantly lower (p &lt;0.0001) in individuals newly diagnosed with CRC, as compared to the control group. Patients who were recently diagnosed and treated for CRC and NAFLD exhibited comparable amounts of vitamin C. The level of vitamin E in control, newly diagnosed CRC and treated CRC patients displayed no significant differences, however comparing with newly diagnosed patients that suffered NAFLD, a significant decrease (p = 0.0014) in the level of vitamin E in CRC with NAFLD group was. The levels of Vitamin D in all groups of patients with colorectal cancer were significantly lower than those in the control group (p &lt;0.0001). Colon cancer patients exhibited significantly decreased levels of vitamin C and D compared to healthy individuals. Vitamins showed potential as diagnostic markers for distinguishing between groups. It is necessary to analyze these findings as the level of serum vitamins may have potential use in the prognosis of the CRC in patients.

The trajectory of vesicular proteomic signatures from HBV-HCC by chitosan-magnetic bead-based separation and DIA-proteomic analysis.

Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer often associated with chronic hepatitis B virus infection (CHB) and liver cirrhosis (LC), underscoring the critical need for biomarker discovery to improve patient outcomes. Emerging as a promising avenue for biomarker development, proteomic technology leveraging liquid biopsy from small extracellular vesicles (sEV) offers new insights. Here, we evaluated various methods for sEV isolation and identified polysaccharide chitosan (CS) as an optimal approach. Subsequently, we employed optimized CS-based magnetic beads (Mag-CS) for sEV separation from serum samples of healthy controls, CHB, LC, and HBV-HCC patients. Leveraging data-independent acquisition mass spectrometry coupled with machine learning, we uncovered potential vesicular protein biomarker signatures (KNG1, F11, KLKB1, CAPNS1, CDH1, CPN2, NME2) capable of distinguishing HBV-HCC from CHB, LC, and non-HCC conditions. Collectively, our findings highlight the utility of Mag-CS-based sEV isolation for identifying early detection biomarkers in HBV-HCC.

SERS and electrochemical dual-mode detection of miRNA-141 by using single Au@Ag nanowire as a new platform.

As biomarkers of cancer, the accurate and sensitive detection of microRNAs is of great significance. Therefore, we proposed a surface-enhanced Raman scattering (SERS)/electrochemical (EC) dual-mode nanosensor for sensitively detecting miRNA-141. The nanosensor uses Au@Ag nanowires as a novel SERS/EC sensing platform, which has the advantages of good biocompatibility, fast response, and high sensitivity. The dual-mode nanosensor can not only effectively overcome the problem of insufficient reliability of single signal, but also realize the amplification and stable output of the detection signal, to ensure the reliability and repeatability of miRNA detection. With this sensing strategy, the target miRNA-141 can be detected over a wide linear range (100 fM to 50 nM) (LOD of 18.4 fM for SERS and 16.0 fM for electrochemical methods). In addition, the process shows good selectivity and can distinguish miRNA-141 from other interfering miRNAs. The actual analysis of human serum samples also proves that our strategy has good reliability, repeatability, and has broad application prospects in the field of analysis and detection.

Prevalence of bluetongue virus disease in a small ruminant population in Kalat, Balochistan, Pakistan

Background and Aim: Bluetongue is a vector-borne, emerging disease that poses a severe threat to most domesticated animals. A cross-sectional study was conducted to estimate the prevalence of bluetongue virus (BTV) disease in apparently healthy sheep and goats in Kalat, Balochistan. Materials and Methods: A total of 270 serum samples (sheep: 150 and goat: 120) were collected and screened for the detection of anti-BTV antibodies using a competitive enzyme-linked immunosorbent assay. The data regarding different contributory risk factors were also collected using a predesigned questionnaire. Results: It revealed that overall, 27.4% (74/270, 95% confidence interval, χ2 = 1.71, p = 0.12) prevalence in both sheep and goat populations. The highest prevalence of 47% (32/68) was recorded in Surab city with the lowest prevalence of 15.49% (11/71) in the Manguchar area. In contrast, in Kalat 28.1% (9/32), Daan area 24% (12/50), and Marap area 22.44% (11/49), seropositivity was recorded. Upon sex bases, antibodies were almost equally found in both male 28.57% (8/28) and female 27.27% (66/242) animal populations. Moreover, all four breeds (Balochi, Khurasani, Lehri, and Rakhshani) were equally and potentially seropositive. The Khurasani breed was the most susceptible to 34.69% (17/49), followed by the Balochi breed, 45/145 (31%) seropositivity. The prevalence of BTV was 16.66% (1/6) in Rakhshani breed and 15.71% (11/70) in Lehri breed., Ticks were found in almost 21% of animals, while 93% of animals were reared on open grazing in rangelands. Conclusion: This study clearly indicates widespread BTV infection in small ruminants in the study area that may pose serious threats to livestock farming. Further extensive studies are recommended to study the prevalence of disease in different agroecological zones of the province. This also warns the high-ups to manage concrete efforts to eradicate and control the disease in the area. Keywords: antibodies, Balochistan, bluetongue virus, competitive enzyme-linked immunosorbent assay, Kalat.

Cryptic transmission and novel introduction of Dengue 1 and 2 genotypes in Colombia

Abstract Dengue fever remains as a public health challenge in Colombia, standing as the most prevalent infectious disease in the country. The cyclic nature of dengue epidemics, occurring approximately every three years, is intricately linked to meteorological events like El Niño Southern Oscillation (ENSO). Therefore, the Colombian system faces challenges in genomic surveillance. This study aimed to evaluate local dengue virus (DENV) transmission and genetic diversity in four Colombian departments with heterogeneous incidence patterns (Department is first level territorial units in Colombia). For this study, we processed 26t6 serum samples to identify DENV. Subsequently, we obtained 118 genome sequences by sequencing DENV genomes from serum samples of 134 patients infected with DENV-1 and DENV-2 serotypes. The predominant serotype was DENV-2 (108/143), with the Asian-American (AA) genotype (91/118) being the most prevalent one. Phylogenetic analysis revealed concurrent circulation of two lineages of both DENV-2 AA and DENV-1 V, suggesting ongoing genetic exchange with sequences from Venezuela and Cuba. The continuous migration of Venezuelan citizens into Colombia can contribute to this exchange, emphasizing the need for strengthened prevention measures in border areas. Notably, the Time to Most Recent Common Ancestor analysis identified cryptic transmission of DENV-2 AA since approximately 2015, leading to the recent epidemic. This challenges the notion that major outbreaks are solely triggered by recent virus introductions, emphasizing the importance of active genomic surveillance. The study also highlighted the contrasting selection pressures on DENV-1 V and DENV-2 AA, with the latter experiencing positive selection, possibly influencing its transmissibility. The presence of a cosmopolitan genotype in Colombia, previously reported in Brazil and Peru, raises concerns about transmission routes, emphasizing the necessity for thorough DENV evolution studies. Despite limitations, the study underscores genomic epidemiology’s crucial role in early detection and comprehension of DENV genotypes, recommending the use of advanced sequencing techniques as an early warning system to help prevent and control dengue outbreaks in Colombia and worldwide.

A self-driven microfluidic immunosensor for rapid separation, enrichment, and detection of biomarkers in serum.

Biomarkers and their concentration levels are critical indicators of metabolomics for clinical applications. Rapid and sensitive analysis methods are essential for realizing timely and efficient quantitation of those significant biomarkers. In this work, a self-driven microfluidic immunosensor was developed for rapid all-in-one separation, enrichment, and detection of biomarkers. This immunosensor was constructed from a cyclic olefin copolymer (COC) channel layer and a polydimethylsiloxane (PDMS) sensing layer. The COC channel layer was modified through protein adsorption, immobilization, and remaining active site blocking. The obtained hydrophilic microchannels not only reduce the nonspecific adsorption, but also provide stable capillary-driven flow generation with linear velocities up to 20mm/s for aqueous solution auto-injection. The PDMS sensing layer was modified using capture antibodies to accomplish affinity recognition of target biomarkers. Procalcitonin (PCT) and serum amyloid A (SAA) were selected as model biomarkers in the feasibility study on applying the self-driven microfluidic immunosensor to bioassay. The limits of detection of PCT and SAA were 7.9ng/L and 7.6μg/L, respectively. Moreover, the whole process can be accomplished within 60min with excellent selectivity and reproducibility. In clinical serum sample analysis, satisfactory recoveries were achieved for PCT and SAA in the ranges of 85.0-103.0% and 95.5-106.0%, respectively, with relative standard deviations less than 5.3%. The method accuracy was further confirmed by the results of commercial immunoassay kits. This simple and easily operated immunosensor provides a rapid and sensitive biomarker analysis tool, and promotes the further development of automated and easy-to-use microfluidic immunoassays.

Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease.

The Alzheimer's disease (AD) affected brain purges K with concurrently increasing serum K, suggesting brain-blood K transferal. Here, natural stable K isotope ratios-δ41K-of human serum samples were characterized in an AD biomarker pilot study (plus two paired Li-heparin and K-EDTA plasma samples). AD serum was found to have a significantly lower mean δ41K relative to controls. To mechanistically explore this change, novel ab initio calculations (Density Functional Theory, DFT) of relative K isotope compositions between hydrated K+ and organically bound K were performed, identifying hydrated K+ as isotopically light (lower δ41K) compared to organically bound K. Taken together with literature, serum δ41K and DFT results are consistent with efflux of hydrated K+ from the brain to the bloodstream, manifesting a measurable decrease in serum δ41K. These data introduce serum δ41K for further investigation as a minimally invasive AD biomarker, with cost, scalability and stability advantages over current techniques.

Effects of compound probiotics on pharmacokinetics of CYP450s probe drugs in rats.

Compound probiotics have been widely used and commonly co-administered with other drugs for treating various chronic illnesses, yet their effects on drug pharmacokinetics remain underexplored. This study elucidated the impact of VSL#3 on the metabolism of probe drugs for cytochrome P450 enzymes (CYP450s), specifically omeprazole, tolbutamide, midazolam, metoprolol, phenacetin and chlorzoxazone. Male Wistar rats were administered with drinking water containing VSL#3 or not for 14 days and then intragastrically administered a CYP450s probe cocktail; This was done to investigate the host CYP450s metabolic phenotype. Stool, liver/jejunum and serum samples were collected for 16S rRNA sequencing, RNA sequencing, and bile acid profiling. The results indicated significant differences in both alpha and beta diversity of intestinal microbial composition between the probiotic and vehicle groups in rats. In the probiotic group, the bioavailability of omeprazole increased by 269.9%, whereas those of tolbutamide and chlorpropamide decreased by 28.1% and 27.4%, respectively. The liver and jejunum exhibited 1,417 and 4,004 differentially expressed genes, respectively, between the two groups. In the probiotic group, most of CYP450s genes were upregulated in the liver but downregulated in the jejunum. The expression of genes encoding metabolic enzymes and drug transporters also changed. The serum conjugated bile acids in the probiotic group were significantly reduced. Shorter duodenal villi and longer ileal villi were found in the probiotic group. In summary, VSL#3 administration altered the gut microbiota, host drug-processing gene expression, and the intestinal structure in rats, which could be reasons for pharmacokinetic changes. Significance Statement This study focused on the effects of the probiotic VSL#3 on the pharmacokinetic profile of CYP450s probe drugs and the expression of host drug metabolism genes. Compared with previous studies, the current study provides a comprehensive explanation for the host drug metabolism profile modified by probiotics, here combined with the bile acid profile and histopathological analysis.

Role of SAA1 in endometrial extracellular matrix remodeling in polycystic ovary syndrome: implication for pregnancy loss.

Abnormal endometrial extracellular matrix (ECM) remodeling compromises endometrial receptivity and diminishes the probability of a successful live birth. Serum amyloid A1 (SAA1), a modulator of inflammation, is elevated in the circulation of polycystic ovary syndrome (PCOS) patients and involved in ECM remodeling during tissue repair. However, the specific role of SAA1 in endometrial ECM remodeling and subsequent risk of pregnancy loss in PCOS patients remains unclear. To examine the role and underlying mechanism of SAA1 in ECM remodeling in the endometrium of PCOS patients. Serum samples from PCOS and control patients were utilized to investigate the relationship between the abundance of SAA1 and pregnancy loss. Human endometrial tissues and primary human endometrial stromal cells were used to examine the role and underlying mechanism of SAA1 in ECM remodeling. Serum SAA1 concentration was elevated and could serve as an independent risk of pregnancy loss in PCOS patients. Increased SAA1 abundance was also observed in endometrium obtained from these patients. Further mechanistic studies showed that SAA1 stimulated collagen I chains synthesis (COL1A1 and COL1A2) in endometrial stromal cells, suggesting excessive SAA1 may contribute to endometrial ECM remodeling, resulting in a non-supportive environment for ongoing pregnancy. This effect was abolished by either a toll-like receptors 2/4 antagonist or a nuclear factor κB inhibitor. The locally elevated levels of SAA1 in endometrium contribute to ECM over-deposition by inducing collagen I synthesis in PCOS patients, which may hamper embryo implantation and increase the risk of pregnancy loss. These observations highlight the crucial role of heightened SAA1 in orchestrating endometrial dysfunction and shed light on potential therapeutic avenues for improving reproductive outcomes in PCOS patients.

The value of human epididymal protein 4, carcinoembryonic antigen and alpha-fetoprotein in the early diagnosis of cervical cancer.

This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. A clinical study Participants: Sixty patients with cervical cancer stage IA-IIA (early-stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Jiaxing First Hospital Methods: Sixty patients with cervical cancer stage IA-IIA (early-stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA and AFP and the clinicopathological characteristics of patients with early-stage cervical cancer were analyzed, and the ROC curves were plotted to identify the value of the single and triple tests of serum HE4, CEA and AFP for the early-stage diagnosis of cervical cancer. The levels of serum HE4, CEA and AFP in the early-stage cervical cancer group were higher than those in the disease control and the healthy control groups (P &lt; 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early-stage cervical cancer (P &lt; 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early-stage cervical cancer were 0.725, 0.679, 0.663 and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (P &lt; 0.05). There is a lack of larger sample sizes to test whether the combined HE4, CEA and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV DNA detection and compare it with the levels of serum markers. The combination of HE4, CEA and AFP has good clinical reference value analysis in the auxiliary diagnosis of early-stage cervical cancer, and it is worthy of further validation and popularization.

Correlative expression of exosomal miRNAs in chemotherapy resistance of triple-negative breast cancer: An observational study.

Drug resistance in tumors is the primary contributor to clinical treatment failures, and aberrant expression of small RNA molecules, specifically microRNAs (miRNAs), in tumor tissues is intricately associated with drug resistance. The aim of this study is to investigate the targets and mechanisms through which exosomal miRNAs from triple-negative breast cancer (TNBC) regulate chemotherapy resistance in tumor cells. Utilizing high-throughput sequencing technology, we conducted exosomal miRNA sequencing on serum samples obtained from TNBC patients who were either sensitive or resistant to AC-sequential T chemotherapy. Subsequently, we identified and screened differentially expressed miRNAs. The observed differences in miRNA expression were further validated through quantitative reverse transcription-polymerase chain reaction. In comparison to TNBC patients who exhibited sensitivity to the AC-sequential T regimen chemotherapy, we identified significant differences in the expression of 85 miRNAs within serum exosomes of patients displaying chemotherapy resistance. Furthermore, we observed a substantial difference in the expression of hsa-miR-6831-5p between TNBC patients who were responsive to chemotherapy and those who were drug-resistant and underwent treatment with the AC-sequential T regimen. hsa-miR-6831-5p holds the potential to serve as a diagnostic marker for assessing the chemosensitivity of the AC-sequential T regimen in TNBC.

Dirofilaria immitis and Dirofilaria repens: Investigating the Prevalence of Zoonotic Parasites in Dogs and Humans in a Hyperenzootic Area

The mosquito-borne zoonotic nematode parasites Dirofilaria immitis and Dirofilaria repens primarily affect dogs. In recent years, their distribution has expanded due to various factors influencing vector-borne pathogens. This study aimed to investigate the comparative prevalence of infection in dogs and humans within a hyperenzootic region of Europe, and to estimate the proportional relationship between infection prevalence in dogs and humans, within the concept of “One Health”. To this end, 604 blood samples from dogs and 625 serum samples from humans living in the Thrace region of northeastern Greece were collected. The dog samples were examined for Dirofilaria spp. microfilariae using Kott’s test and for D. immitis antigen using a commercial serological test. The human sera were analyzed for both parasites by Western blot. The overall prevalence of infection in dogs was 177 (29.3%), with 173 (28.6%) testing positive for D. immitis and 7 (1.2%) for D. repens, including 6 (1%) cases of mixed infection. Specific IgG antibodies were detected in 42 (6.7%) human samples, with 24 (3.8%) positive for D. immitis and 18 (2.9%) for D. repens. The infection proportion in humans was 23.4% of the corresponding canine infections, indicating a high risk of human infection in this hyperenzootic region.

Highly sensitive CD40L protein discrimination via label-free fiber sensing technologies.

The recombinant Cluster of Differentiation 40 Ligand (CD40L) can be expressed in various cells and is closely related to various types of cancer. This association underscores the critical need for expedited and precise measurement of CD40L levels in clinical fluid specimens. A novel optical fiber biosensor has been devised, employing single-mode fibers that are sandwiched around a coreless fiber, with the diameter refined by etching with hydrogen fluoride. This innovative configuration allows for light transmission through the evanescent field, thereby enhancing the sensor's sensitivity to changes in the surrounding refractive index. Employing chemical binding techniques, CD40 was securely immobilized onto the fiber's surface, facilitating the detection of CD40L. The sensor exhibited a sensitivity of 1.126 nm (μg mL-1)-1 and a detection limit of 0.68 nM. Furthermore, the sensor's specificity for CD40L was validated using authentic clinical serum samples spiked with artificial analytes. In addition, the specificity of CD40L of the proposed sensor was proved using natural clinical serum samples with added artificial analyte, assisted by the ELISA method, and the results ideally conformed with the detection of standard samples. With the aid of the ELISA method, the outcomes were found to be in excellent agreement with those from standard sample detection. Consequently, the findings indicate that this sensor provides a specific, label-free, and highly sensitive method for CD40L detection, showcasing its significant potential for applications in molecular biology research.