Alpha-fetoprotein Concentration Research Articles

Intramolecular fluorescence resonance energy transfer strategy for accurate detection of AFP-L3% and improved diagnosis of hepatocellular carcinoma

Early and accurate diagnosis of hepatocellular carcinoma (HCC) is of significant importance for improving the survival rate and quality of life for HCC patients. The combined detection of alpha-fetoprotein (AFP) and alpha-fetoprotein-L3 (AFP-L3), namely AFP-L3%, can greatly improve the accuracy of HCC diagnosis compared with AFP detection. Herein, we developed a novel intramolecular fluorescence resonance energy transfer (FRET) strategy for sequential detection of AFP and AFP-specific core fucose to improve the diagnosis accuracy of HCC. Firstly, fluorescence-labeled AFP aptamer (AFP Apt-FAM) was used to specifically recognize all AFP isoforms, and total AFP was quantitatively determined using fluorescence intensity of FAM. Then, 4-((4-(dimethylamino)phenyl)azo)benzoic acid (Dabcyl) labeled lectins (PhoSL-Dabcyl) were used to specifically recognize the core fucose expressed on AFP-L3 that does not bind to other AFP isoforms. The combination of FAM and Dabcyl on the same AFP molecule could generate FRET effect, thereby quenching the fluorescence signal of FAM and quantitatively determining AFP-L3. After that, AFP-L3% was calculated according to the ratio of AFP-L3 to AFP. With this strategy, the concentration of total AFP, AFP-L3 isoform as well as the AFP-L3% were sensitively detected. Detection limits of 0.66 and 0.186 ng/mL were obtained for AFP and AFP-L3 in human serum, respectively. Clinical human serum test results showed that AFP- L3 % test was more accurate than AFP assay to distinguish healthy people, HCC patients and benign liver disease patients. Therefore, the proposed strategy is simple, sensitive and selective, which can improve the accuracy of early diagnosis of HCC, and has good clinical application potential.

A new portable toluidine blue/aptamer complex-on-polyethyleneimine-coated gold nanoparticles-based sensor for label-free electrochemical detection of alpha-fetoprotein.

The quantification of alpha-fetoprotein (AFP) as a potential liver cancer biomarker which is generally found in ultratrace level is of significance in biomedical diagnostics. Therefore, it is challenging to find a strategy to fabricate a highly sensitive electrochemical device towards AFP detection through electrode modification for signal generation and amplification. This work shows the construction of a simple, reliable, highly sensitive, and label-free aptasensor based on polyethyleneimine-coated gold nanoparticles (PEI-AuNPs). A disposable ItalSens screen-printed electrode (SPE) is employed for fabricating the sensor by successive modifying with PEI-AuNPs, aptamer, bovine serum albumin (BSA), and toluidine blue (TB), respectively. The AFP assay is easily performed when the electrode is inserted into a small Sensit/Smart potentiostat connected to a smartphone. The readout signal of the aptasensor derives from the electrochemical response of TB intercalating into the aptamer-modified electrode after binding with the target. The decrease in current response of the proposed sensor is proportional to the AFP concentration due to the restriction of the electron transfer pathway of TB by a number of insulating AFP/aptamer complexes on the electrode surface. PEI-AuNPs improve SPE's reactivity and provide a large surface area for aptamer immobilization whereas aptamer provides selectivity to the target AFP. Consequently, this electrochemical biosensor is highly sensitive and selective for AFP analysis. The developed assay reveals a linear range of detection from 10 to 50000pgmL-1 with R 2 = 0.9977 and provided a limit of detection (LOD) of 9.5pgmL-1 in human serum. With its simplicity and robustness, it is anticipated that this electrochemical-based aptasensor will be a benefit for the clinical diagnosis of liver cancer and further developed for other biomarkers analysis.

Application of a Novel One-Side Cell Quartz Crystal Microbalance Immunosensor in the Determination of Alpha-Fetoprotein from Human Serum.

The rapid and accurate detection of alpha-fetoprotein (AFP) levels is of great significance for the diagnosis and later treatment evaluation of liver cancer. In this study, a novel integrated quartz crystal microbalance (QCM) immunosensor based on the design to contact liquids on one side only was developed for the label-free detection of AFP. Anti-AFP mouse monoclonal antibodies were immobilized onto the upper electrode surface of the pre-treatment crystals using the staphylococcus aureus protein A. The AFP antigens in human serum were captured by specific surface-coated antibodies, and testing was carried out by monitoring the corresponding changes in frequency. The concentration range of the antigen detected was 13-760 ng/mL. The frequency characteristics of the process of antibody immobilization were investigated in detail, and high reproducibility of AFP antibody immobilization was achieved (standard deviation (SD) = 2.2 Hz). The developed QCM measurement system demonstrated a short test time (only 30 min), good reproducibility (the biological activity can still maintain more than 90% of the first test till it is reused five times), and accuracy as good as the one achieved with the radioimmunoassay (the maximum relative deviation = 4.8%). The designed QCM test system can easily and quickly detect AFP concentrations up to 760 ng/mL, indicating that the developed QCM assay is likely to lead to an alternative approach in large-scale screening for liver cancer in the near future.

Fascinating Immobilization-Free Electrochemical Immunosensing Strategy Based on the Cooperation of Buoyancy and Magnetism.

Rapid and accurate detection of biomolecules is of vital importance for the diagnosis of disease and for performing timely treatments. The point-of-care analysis of cancer biomarkers in the blood with low cost and easy processing is still challenging. Herein, an advanced and robust strategy, which integrates the buoyant recognition probe with the magnetic reporter probe in one solution, was first proposed for immobilization-free electrochemical immunosensing. The tumor marker of alpha fetoprotein (AFP) can be captured immune-buoyantly, and then a multifunctional magnetic reporter probe in pseudo-homogeneous solution was further captured to fulfill a sandwich-type immunoreaction. The residual magnetic reporter probe can be firmly and efficiently attracted on a magnetic glassy carbon electrode to fulfill the conversion of the target AFP amount into the residual magnetic electrochemical signal indicator. As a result, the electrochemical signal of methylene blue can accurately reflect the original level of target antigen AFP concentration. By integrating buoyancy-driven quasi-homogenous biorecognition with magnetism-mediated amplification and signal output, the proposed immobilization-free electrochemical immunosensing strategy displayed a wide range of linear response (100 fg mL-1 to 10 ng mL-1), low detection limit (14.52 fg mL-1), and good reproducibility, selectivity, and stability. The designed strategy manifests remarkable advantages including assay simplicity, rapidness, and high sensitivity owing to the in-solution instead of on-electrode biorecognition that could accelerate and improve the biorecognition efficiency. To the best of our knowledge, this is the first cooperation of buoyancy-driven biorecognition with magnetism-mediated signal output in bioanalysis, which would be attractive for rapid clinic biomedical application. Thus, this work provides a fresh perspective for convenient and favorable immobilization-free electrochemical biosensing of universal biomolecules.

A simple, sensitive, label-free electrochemical immunosensor based on the chitosan-coated silver/cerium oxide (CS@Ag/CeO2) nanocomposites for the detection of alpha-fetoprotein (AFP)

Metal oxide-based sensors have the benefit of inexpensive, quick response, and high sensitivity in detecting specific biological species. In this article, a simple electrochemical immunosensor was fabricated using antibody-chitosan coated silver/cerium oxide (Ab-CS@Ag/CeO2) nanocomposites on a gold electrode for sensitive alpha-fetoprotein (AFP) diagnosis in human serum samples. Successfully synthesis of AFP antibody-CS@Ag/CeO2 conjugates was confirmed through Fourier transform infrared spectra of the prototype. The amine coupling bond chemistry was then used to immobilize the resultant conjugate on a gold electrode surface. It was observed that the interaction of the synthesized Ab-CS@Ag/CeO2 nanocomposites with AFP prevented an electron transfer and reduced the voltammetric Fe(CN)6 3−/4− peak current, which was proportional to the amount of AFP. The linear ranges of AFP concentration were found from 10−12–10−6 g.ml−1. The limit of detection was calculated using the calibration curve and came out to be 0.57 pg.ml−1. The designed label-free immunosensor successfully detected AFP in human serum samples. As a result, the resulting immunosensor is a promising sensor plate form for AFP detection and could be used in clinical bioanalysis.

Surgical treatment of hepatocellular carcinoma after Fontan operation: three case reports and review of the literature.

We herein describe three patients with Fontan-associated liver disease who developed hepatocellular carcinoma (HCC). The first patient was a 28-year-old woman who had undergone the Fontan operation (FO) at the age of 4years. She was diagnosed with HCC (cT4aN0M0, Stage IVA, UICC 8th edition), for which she underwent extended posterior right sectionectomy and partial hepatectomy of S2. She developed recurrence of peritoneal dissemination after 12months, and she was alive 18months after surgery. The second patient was a 43-year-old man who had undergone the FO at the age of 3years. He was diagnosed with HCC (cT2N0M0, Stage II), for which he underwent laparoscopic-assisted partial hepatectomy of S3. He remained free from recurrent HCC for 17months. The third patient was a 21-year-old woman who had undergone the FO at the age of 3years. She was diagnosed with HCC (cT3N0M0, Stage III), for which she underwent laparoscopic-assisted partial hepatectomy of S2 and S4. She remained free from recurrent HCC for 30months. We reviewed 18 surgical cases of HCC arising from Fontan-associated liver disease, including our 3 cases, and found that a high preoperative alpha-fetoprotein concentration might be a predictor of HCC recurrence.

The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

Construction of a competitive electrochemical immunosensor based on sacrifice of Prussian blue and its ultrasensitive detection of alpha-fetoprotein

Effective signal amplification is a prerequisite for ultrasensitive detection by electrochemical immunosensors. For quantitative and ultrasensitive detection of alpha-fetoprotein (AFP), we designed a competitive electrochemical immunosensor and transferred the immunoreactivity from the electrode surface to the cuvette. AFP antigen was captured using AFP primary antibody (Ab1) immobilized on magnetic nanobeads (MBs), and ZIF-8 nanomaterials attached to secondary antibody (Ab2) were used as probes. MBs helped retain the sandwich structure in the test tube through incubation and washing steps. Then, an appropriately fixed excess of sodium ethylenediaminetetraacetic acid (EDTA) solution was added to the cuvettes, resulting in etching of Zn ions from ZIF-8 and formation of Zn-EDTA complexes. After magnetic separation, a certain amount of supernatant is added dropwise to the Prussian blue (PB)-modified electrode (GCE), and Fe ions (from PB) complex with the remaining EDTA in the supernatant, thus reducing the signal response value of PB. The higher the AFP concentration, the lower the amount of free EDTA in the supernatant, the less the destruction of PB, and therefore the higher the current. Under optimal conditions, the immunosensor achieved ultra-sensitive detection of AFP in the range of 10−4 ng/mL-100 ng/mL with a limit of detection (LOD) as low as 0.032 pg/mL (S/N = 3). The excellent performance provides an important tool for the early screening and detection of AFP.

A graphene-assisted electrochemical sensor for detection of alpha-fetoprotein in serum

Alpha fetoprotein (AFP) is a specific tumor marker for the diagnosis of primary liver cancer. In this work, a molecularly imprinted (MIP) electrochemical sensor for AFP was prepared by surface imprinting method. The MIP electrochemical biosensor uses polysulfide cordial and graphene-gold composite as electrode modified nanomaterials to effectively enhance the detection of electrical signals. Dopamine (DA) is the functional monomer and the PDA-AFP complex is obtained by electropolymerization. The eluent elutes the functional monomer and the specific cavity formed can adsorb the target molecule. Under optimal experimental conditions, differential pulse voltammetry (DPV) was used for detection. The current of the prepared biosensor decreases with increasing AFP concentration. The peak current value of DPV assay showed good linearity with the logarithm of AFP concentration in the range of 0.01 ng/mL-1000 ng/mL. The detection limit can reach 3.7 pg/mL.

A rare primary thyroid mixed germ cell tumour: a case report

Germ cell tumours mostly occur in the gonads. Extragonadal site is rare and mainly located in the mediastinum, retroperitoneum and pineal gland. Germ cell tumour that occurs in the thyroid gland is extremely rare. We present our first description of a patient with a mixed germ cell tumour located primarily in the thyroid gland. A 35 years old gentleman presented with two months history of thyroid swelling associated with compressive symptoms. His neck ultrasound showed multinodular goiter with suspicious nodule (TR4) and FNAC revealed highly suggestive of a malignant lesion. Subsequently, the thyroid mass progressively enlarged in size causing acute upper airway obstruction that made him collapsed at Emergency Department. Core biopsy of TR4 thyroid nodule suggestive of malignant lesion which could be mixed germ cell tumour or poorly differentiated carcinoma. Abnormal laboratory tests showed a high concentration of LDH, Alpha fetoprotein and beta-HCG. He underwent emergency total thyroidectomy, debulking and tracheostomy. Histopathology reported the mass composed of mixed non-seminomatous germ cell tumour with area of necrosis (30%), primarily immature elements (80%), yolk sac tumour (15%) and embryonal carcinoma (5%). He was scheduled for chemotherapy post operatively however he succumbed to the illness due to advanced tumour and sepsis.

Clinical value of serum AFP and PIVKA‐II for diagnosis, treatment and prognosis of hepatocellular carcinoma

The accuracy of alpha-fetoprotein (AFP) as a diagnostic marker for hepatocellular carcinoma (HCC) is insufficient, and the application of abnormal prothrombin (PIVKA-II) in HCC is still controversial. Serum AFP and PIVKA-II levels were analyzed in 145 cases of HCC, 57 of benign liver disease, 55 of cholangiocarcinoma and gallbladder carcinoma, 112 of other gastrointestinal tumors with liver metastasis, and 101 healthy controls. Receiver operating characteristic curve and area under the curve were used to evaluate the diagnostic value of AFP and PIVKA-II for HCC. The changes in serum AFP and PIVKA-II levels before and after treatment in 47 HCC patients who underwent surgery and 77 who received interventional treatment were used to evaluate treatment efficacy and prognosis in HCC. The concentrations of AFP and PIVKA-II in the HCC group were significantly higher than those in other groups (p < 0.01). The diagnostic value of PIVKA-II in HCC was better than that of AFP, and combined detection improved the diagnostic sensitivity and specificity. The levels of AFP and PIVKA-II after liver cancer surgery were significantly lower than those before surgery. Elevated levels of PIVKA-II before surgery predicted disease progression, and patients who remained positive for PIVKA-II after surgery had worse prognosis than those who became negative after surgery. Combined detection of AFP and PIVKA-II is superior to both tests alone. We found that higher serum level of PIVKA-II indicates more severe HCC, with worse prognosis, while the level of AFP had no correlation with the prognosis.

History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients.

This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.

Simvastatin Induces Apoptosis And Suppresses Hepatocellular Carcinoma Induced In Rats

Hepatocellular carcinoma (HCC) is a frequent primary aggressive cancer, a crucial cause of cancer-related mortality globally. Simvastatin is a well-known safe cholesterol-lowering medication that has been recently shown to suppress cancer progression. Apoptosis is a well-organized and controlled cellular process that happens both physiologically and pathologically leading to executing cell death. Apoptosis is frequently downregulated in cancer cells. In the present study, we aimed to test the effect of simvastatin on HCC progression. HCC was induced in experimental rats by means of diethylnitrose amine (DEN) and thioacetamide (TAA) injections. Gross examination and liver index along with biochemical analysis of hepatic function were evaluated. Serum alpha-feto protein (AFP) concentration was measured by ELISA. Histopathological examination was used for assessing necroinflammatory scores and fibrosis degree. Apoptosis was assessed using immunohistochemistry (IHC) and quantitative PCR (qPCR). Simvastatin was found to induce apoptosis successfully in HCC and improve liver fibrosis, overall hepatic function, and necroinflammatory score. Simvastatin, therefore, may be a potential adjunctive therapeutic option in clinical settings of treating HCC.

A sandwich-like configuration with a signal amplification strategy using a methylene blue/aptamer complex on a heterojunction 2D MoSe2/2D WSe2 electrode: Toward a portable and sensitive electrochemical alpha-fetoprotein immunoassay.

Liver cancer is one of the most common global health problems that features a high mortality rate. Alpha-fetoprotein (AFP) is a potential liver cancer biomarker for the diagnosis of liver cancer. The quantitative detection of AFP at an ultratrace level has important medical significance. Using the reaction of the antibody-antigen pair in an immunosensor enables the sensitive and selective AFP assay. Finding a strategy in signal generation and amplification is challenging to fabricate new sensitive electrochemical immunosensors for AFP detection. This study demonstrates the construction of a simple, reliable, and label-free immunosensor for the detection of AFP on a smart phone. Exfoliated two-dimensional (2D) molybdenum diselenide (MoSe2) and 2D tungsten diselenide (WSe2) were employed to modify the disposable screen-printed carbon electrode (SPCE) to use as the electrochemical platform, which is affixed to a small potentiostat connected to a smart phone. The modified electrode offers antibody immobilization and allows detection of AFP via an immunocomplex forming a sandwich-like configuration with the AFP-corresponding aptamer. A heterojunction 2D MoSe2/2D WSe2 composite improves the SPCE's reactivity and provides a large surface area and good adsorption capacity for the immobilizing antibodies. The signal generation for the immunosensor is from the electrochemical response of methylene blue (MB) intercalating into the aptamer bound on the electrode. The response for the proposed sandwich-like immunosensor is proportional to the AFP concentration (1.0-50,000 pg ml-1). The biosensor has potential for the development of a simple and robust point-of-care diagnostic platform for the clinical diagnosis of liver cancer, achieving a low limit of detection (0.85 pg ml-1), high sensitivity, high selectivity, good stability, and excellent reproducibility.

A Retrospective Multicentric Study of 34 Patients with Niemann–Pick Type C Disease and Early Liver Involvement in France

To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder. Patients with genetically confirmed NP-C (NPC1, n=31; NPC2, n=3) and liver involvement before age 6months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining. At initial evaluation (median age, 17days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6months of life, including 3 from liver involvement. In patients who survived beyond age 6months (median follow-up, 6.1years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients. Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.

The Value of MRI Combined with AFP, AFP-L3, GP73, and DCP in the Diagnosis of Early Primary Liver Cancer.

Objective To investigate the diagnostic value of magnetic resonance imaging (MRI) combined with serum alpha-fetoprotein (AFP), alpha-fetoprotein (AFP-L3), Golgi protein 73 (GP73), and des-γ-carboxyprothrombin (DCP) on early-stage primary liver cancer (PHC). Methods A total of 122 patients who were treated in our hospital from January 2019 to May 2022 were included in this study, including 62 patients with early PHC (referred to as the observation group) and 60 patients with benign liver disease (referred to as the control group). MRI scans were performed on all participants, and MRI image features were compared. Subsequently, the differences in serum AFP, AFP-L3, GP73, and DCP concentrations of the two groups of patients were detected and compared. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of MRI and each of the above tumor markers in diagnosing early PHC. Results The proportion of low or slightly low signal on T1WI in the observation group was significantly greater than that in the control group, while the proportions of equisignal and high signal were lower than those in the control group. The proportion of high signal on T2WI and high signal on DWI in the observation group was higher than that in the control group, while the proportion of low or slightly low signal and equisignal was lower than that in the control group. Compared with the control group, the serum concentrations of AFP, AFP-L3, GP73, and DCP in the observation group were significantly increased (all P < 0.05). For the diagnosis of early-stage PHC patients, MRI combined with these four markers showed favorable diagnostic value compared with parameter alone (area under the ROC curve, sensitivity, and specificity were 0.943, 0.919, and 0.833, respectively). Conclusion MRI combined with serum AFP, AFP-L3, GP73, and DCP detection has good value in the diagnosis of early PHC patients, and can serve as an effective strategy to improve the early diagnosis rate of PHC.

High-Risk Pregnancy Is Associated With Increased Alpha-Fetoprotein Concentrations in the Amniotic Fluid and Foal Plasma

This study aimed to determine alpha-fetoprotein (AFP) concentrations in amniotic fluid, plasma of mares and respective foals: carrying normal pregnancies and delivering healthy foals (n = 20; Group 1); carrying apparently normal pregnancies and delivering sick foals (n = 15; Group 2); carrying high-risk pregnancies and delivering sick foals (n = 14; Group 3). High-risk pregnancy was defined by a history of premature udder development/lactation or increased of the combined thickness of the uterus and placenta, or vulvar discharge and/or mares' systemic illness. Sick foals were affected by neonatal encephalopathy, sepsis, prematurity/dysmaturity, or hypoxic-ischemic encephalopathy. Based on histological examination of the chorioallantois, AFP trend was analyzed in pregnancies with pathologic (PFM) and normal fetal membranes (NFM). Concentrations of AFP were measured using a commercially available immunoassay previously validated for horses. Mares' plasma AFP did not change during the last 15–20 days of pregnancy in the three groups, and there was no difference among them. Amniotic fluid AFP was higher in Group 3 (P = .014). Foals’ plasma AFP concentration was higher from birth to 72hours in foals of Group 2 and 3 than in healthy ones, and foals of Group 3 had the highest value. The strong association (r = 0.84; P < .0001) between AFP in amniotic fluid and foals' plasma at birth is likely due to the presence of AFP in fetal urine. AFP was higher in pregnancy with PFM than with NFM in mare's plasma at admission (P = .031), amniotic fluid (P = .004), foal's plasma at birth (P = .002), at 24 (P = .005) and at 72 hours of life (P = .004). AFP is higher in pregnancy with histopathological lesions of the chorioallantois providing the evidence of the differences between pregnancy with a normal placental barrier and the more compromised ones. The increased AFP concentration in the amniotic fluid and plasma of high-risk foals suggests upregulation.

Ionic liquid functionalized trapezoidal Zn-MOF nanosheets integrated with gold nanoparticles for photoelectrochemical immunosensing alpha-fetoprotein

An imidazolium based ionic liquid was successfully prepared and used as an organic ligand to coordinate with Zn2+ to prepare trapezoidal metal-organic frameworks (Zn-MOF) nanosheets. Then, gold nanoparticles (AuNPs) were integrated onto Zn-MOF nanosheets surface to produce AuNPs@Zn-MOF nanocomposites by in-situ reduction of chloroauric acid. AuNPs with size less than 5 nm were uniformly dispersed on the entire surface of Zn-MOF nanosheets. AuNPs can significantly promote the photocurrent response of Zn-MOF nanosheets and supply an efficient photoelectrochemical sensing platform for fabricating an immunosensor for alpha-fetoprotein (AFP). For AFP determination, the photocurrent response of the immunosensor was linearly related to the logarithm of AFP concentration in the range of 0.005–15.0 ng/mL. The detection limit was calculated to be 1.88 pg/mL. The PEC immunosensor can be facilely fabricated, and provided some superior analytical characteristics such as excellent selectivity, sensitivity, stability and reproducibility for AFP determination. Practicability of the photoelectrochemical immunosensor was demonstrated by using it in assaying AFP in clinical serum samples.

The predictive value of maternal serum AFP to PAPP-A or b-hCG ratios in spontaneous preterm birth

The use of the second trimester alpha-fetoprotein (AFP) along with the first trimester pregnancy-associated plasma protein-A (PAPP-A) has been found to be useful in the estimation of unfavourable pregnancy outcome. Our aim in this study was to determine the relationship between maternal PAPP-A and b-hCG and AFP concentrations in spontaneous preterm birth (sPTB). This prospective cohort study included 372 singleton pregnancies with PAPP-A, b-hCG and AFP levels in the first trimester, which were converted to multiples of the median (MoM). The predictive ability of AFP-to-PAPP-A and AFP-to-b-hCG ratios for sPTB was evaluated. The risk for sPTB ≤34 weeks increased in women with AFP-to-PAPP-A ratio >7 (OR 2.9, 95% CI 1.2–6.4). Women with AFP-to-b-hCG ratio >0.6 had a 3.5-fold higher risk for sPTB ≤32 weeks. Increased maternal AFP-to-PAPP-A or AFP-to-b-hCG ratios in the first trimester may help to predict pregnant women at high risk for sPTB, and this may be beneficial in developing management plans. Impact Statement What is already known on this subject? There is a synergistic association between the combination of low pregnancy-associated plasma protein-A (PAPP-A) in the first trimester with alpha-fetoprotein (AFP) in the second trimester with subsequent development of PTB. Maternal serum biochemical markers measured as a part of aneuploidy screening are reflective of pregnancy adverse outcomes related with placental insufficiency. PAPP-A and AFP have a low predictive ability to determine women at high risk for preterm birth. What do the results of this study add? Elevated AFP:PAPP-A or AFP:B-HCG ratio in the first trimester is associated with increased risk for sPTB. The ratios of these biochemical markers in the first trimester may be beneficial to identify women at high risk for sPTB. What are the implications of these findings for clinical practice and/or further research? The ratios may predict pregnant women at high risk for sPTB, and such risk may be helpful in the development of a management plan. Incorporation of AFP:PAPP-A or AFP:B-HCG ratios in the first trimester may help to improve the screening efficacies, and provide a simple alternative tool.

Terahertz metamaterial biosensor for diagnosis of hepatocellular carcinoma at early stage.

We propose a method for diagnosis of cirrhosis and hepatocellular carcinoma (HCC) by using a terahertz (THz) metamaterial (MM) biosensor. The biosensor has a resonance frequency at about 0.801 THz and can measure the concentration of alpha-fetoprotein (AFP) in serum. The sensitivity of the sensor is 124 GHz/refractive index unit (RIU), and the quality-factor (Q) is 6.913, respectively. When the surface of the biosensor is covered with healthy serum (AFP≤7ng/mL), the maximum resonance frequency shift is 50 GHz. However, when it is covered with serum from patients with cirrhosis and early HCC (AFP>7ng/mL), the resonance frequency shift is more than 59 GHz. Positive correlation exists between the frequency shift of the biosensor and serum levels of the AFP in the HCC patients. This study provides a method for quick diagnosis and prediction of cirrhosis and HCC.