Hepatocyte Aquaporin 8-mediated Water Transport Facilitates Bile Dilution and Prevents Gallstone Formation in Mice.

BACKGROUND AND AIMS: Although water channel aquaporin-8 (AQP8) has been implicated in hepatic bile formation and liver diseases associated with abnormal bile flow in human and animal studies, direct evidence of its involvement in bile secretion is still lacking. This study aimed to determine the role of AQP8 in bile secretion and gallstone formation. METHODS: We generated various transgenic knock-in and knockout mouse models and assessed liver AQP8 expression by immunostaining and immunoblotting, hepatic bile secretion by cannulation of the common bile duct, cholesterol gallstone formation by feeding a high-fat lithogenic diet, and identified regulatory small molecules by screening the organic fractions of cholagogic Chinese herbs and biochemical characterization. RESULTS: We identified a novel expression pattern of AQP8 protein in the canalicular membrane of approximately 50% of the liver lobules. AQP8-deficient mice exhibited impaired hepatic bile formation, characterized by the secretion of concentrated bile with a lower flow rate and higher levels of bile lipids than that of wild-type littermates. AQP8-/- mice showed accelerated gallstone formation, which was rescued by AAV-mediated hepatic expression of AQP8 or AQP1. Moreover, we identified a small molecule, scutellarin, that upregulates hepatocyte AQP8 expression in vitro and in vivo. In AQP8+/+ mice, scutellarin significantly increased bile flow, decreased bile lipid concentrations, and prevented gallstone formation compared to AQP8-/- mice. Molecular studies revealed that scutellarin promoted the ubiquitination and degradation of HIF-1α, a transcriptional negative regulator of AQP8, by disrupting its interactions with HSP90. CONCLUSIONS: AQP8 plays a crucial role in facilitating water transport and bile dilution during hepatic bile formation, thereby mitigating gallstone formation in mice. Small-molecule intervention validated hepatocyte AQP8 as a promising drug target for gallstone therapy. IMPACT AND IMPLICATIONS: The incidence of gallstone disease is high, and current drug treatments for gallstones are very limited, necessitating the identification of novel drug targets for developing new drugs with universal applicability. To our knowledge, this is the first study to provide direct evidence that hepatic water channel AQP8 plays a key role in bile dilution and gallstone formation. Modulation of hepatic water transport may provide a universal therapeutic strategy for all types of gallstone diseases.

Integration of network pharmacology and transcriptomics to explore the mechanism of isoliquiritigenin in treating heart failure induced by myocardial infarction.

BACKGROUND: The inflammatory response and myocardial remodeling play critical roles in the progression of heart failure (HF) following myocardial infarction (MI). Isoliquiritigenin (ISL) possesses anti-inflammatory properties and has been investigated in cardiovascular diseases such as atherosclerosis. However, the effects and mechanism of ISL on MI-induced HF remain unclear. This research aimed to explore the effects and mechanism of ISL in the treatment of HF on the basis of network pharmacology, transcriptomics, and experimental verification. METHODS AND RESULTS: We established an MI-induced HF mouse model in which ISL was administered via gavage for 28 days. Ultrasonic cardiogram data were collected from the mice, and pathological staining was conducted. Then, network pharmacology and molecular docking were performed. Transcriptomic analysis was also conducted on mouse myocardial tissue. Ultimately, we integrated transcriptomic data and network pharmacology to reveal the underlying mechanism, with the results verified through in vivo experiments. Our experiments indicated that ISL improved cardiac function, preserved myocardial structure, inhibited collagen fiber accumulation, reduced inflammatory factor secretion, and mitigated myocardial cell apoptosis in mice with MI-induced HF. A combination of transcriptomics and network pharmacology analysis revealed that core targets of ISL related to HF were significantly enriched in the Tumor Necrosis Factor (TNF) signaling pathway. Molecular docking validation demonstrated that ISL shows strong binding to these core targets. Additionally, in vivo experiments verified that ISL protects against HF post-MI by inhibiting the TNF signaling pathway. CONCLUSION: We clarified the anti-inflammatory and antimyocardial remodeling mechanisms of ISL in the treatment of HF post-MI, which involves the TNF signaling pathway.

The effect of heat treatment on the lactosylation of milk proteins.

Protein lactosylation is a significant modification that occurs during the heat treatment of dairy products, causing changes in proteins' physical-chemical and nutritional properties. Knowledge of the detailed lactosylation information on milk proteins under various heat treatments is important for selecting appropriate thermo-processing and identifying markers to monitor heat load in dairy products. In the present study, we used proteomics techniques to investigate lactosylated proteins under different heating temperatures. We observed a total of 123 lactosylated lysines in 65 proteins, with lactosylation even occurring in raw milk. The number of lactosylated lysines and proteins increased moderately at 75°C to 130°C, but dramatically at 140°C. We found that 6 out of 10, 9 out of 16, 6 out of 12, and 5 out of 15 lysine residues in κ-casein, ß-lactoglobulin, α-lactalbumin, and αS1-casein, respectively, were lactosylated under the applied heating treatment. Moreover, different lactosylation states of individual lysines and proteins can indicate the intensity of heating processes. Lactosylation of K14 in ß-lactoglobulin could distinguish pasteurized and UHT milk, while lactosylation of lactotransferrin can reflect moderate heat treatment of products.

[Bacterial Endotoxin for Intrathoracic Medical Devices Requirement Revisited].

Bacterial endotoxin is considered as one of the critical risk factors in medical devices, especially implanted devices that directly or indirectly contact with blood circulating system. In that case, endotoxin limits for implanted medical devices is important in determine the safety of medical devices. According to GB/T 14233.2-2005, the requirements of endotoxin index for intrathoracic medical devices is 2.15 EU per device. However, the definition of "intrathoracic medical devices" is vague. Specifically, "for cardiovascular system application" instead of "intrathoracic application" is more reasonable. With the deeper understanding of the risk of endotoxin in medical devices and considering the internationally accepted standards, the limits of endotoxin in medical devices for cardiovascular system application is acceptable at 20 EU per device.

Klotho ameliorates diabetic nephropathy by activating Nrf2 signaling pathway in podocytes.

Oxidative stress plays a key role in the pathogenesis of diabetic nephropathy (DN). The anti-aging protein Klotho has been demonstrated to have antioxidant capacity. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating antioxidant responses. The present study aimed to explore the effects of Klotho on DN and the underlying mechanisms related to Nrf2. Low glucose (LG) or high glucose (HG) medium-cultured podocytes and diabetic db/db mice were overexpressed with Klotho via adenoviral transfer to evaluate the effects of Klotho on Nrf2 signaling, oxidative stress, podocyte apoptosis, and renal function and histopathology. Klotho overexpression significantly induced the expression and activation of Nrf2 as well as its downstream targets SOD2 and NQO1 in podocytes. Moreover, Klotho overexpression inhibited HG-induced oxidative stress and apoptosis in podocytes. Co-treatment with Nrf2 inhibitor trigonelline prevented Klotho-induced expression of SOD2 and NQO1, and abolished Klotho-conferred antioxidant and anti-apoptotic effects. In db/db mice, Klotho overexpression also activated Nrf2 signaling, and suppressed diabetes-induced oxidative stress and podocyte apoptosis, which were accompanied by improved renal function and decreased glomerulosclerosis. Our data highlight a novel Nrf2-mediated antioxidant mechanism underlying the protective effects of Klotho in podocytes and indicate the therapeutic potential of targeting Klotho to activate Nrf2 in DN.

Double 3-Ethyl-2,4-dimethylpyrrole Configured Fluorescent Dye with Fluorine-Boron as the Bridge.

Dipyrrolydiketones BF2 complex was synthesized and characterized by NMR, HRMS, and single crystal diffraction. In non-polar environment, this BF2 containing dye emitted bright blue-green fluorescence. No significant spectra shift was observed both in absorption and emission spectra, which indicates the insensitivity of absorption/emission toward environment. The alkyl substituted pyrrole rings lead to its highly emission character in solid state by enhancing the distance between dye molecules. Absolute quantum yields were determined to be 0.51-0.78/0.36 in selected organic medium and solid state, respectively. The emission dynamics was investigated by fluorescence lifetime and both monoexponential and bi-exponential decay was observed.

[Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases].

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

ApoL1 induces kidney inflammation through RIG-I/NF-κB activation.

The genetic variations of the apolipoprotein L1 (APOL1) gene are associated with non-diabetic kidney diseases. However, very little is known about the role of ApoL1 in glomerular damage. Here, we aimed to identify the function and mechanism of ApoL1 in glomerular damage. The mice were randomly divided into two groups: one group was intraperitoneally injected with phosphate buffer saline (PBS), while the other group was intraperitoneally injected with recombinant ApoL1 every other day for 3 months. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were used to demonstrate the effects of ApoL1 on kidney inflammation and injury. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses revealed that ApoL1-treated mice exhibited enhanced expression of various inflammation markers in the kidney and serum compared to the PBS-treated mice. Immunofluorescence staining revealed that ApoL1 accumulated in kidney podocytes. Treatment with ApoL1 dose-dependently increased the expression of inflammation markers and apoptotic markers. The abnormal gene expression associated with ApoL1-mediated podocyte inflammation was evaluated using microarray analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the upregulated genes were enriched in the inflammation-related processes, such as the RIG-I/NF-κB signaling pathway. Consistently, the knockdown of RIG-I significantly mitigated the ApoL1-induced upregulation of inflammatory and apoptotic markers in the human podocytes. Additionally, the ApoL1-induced glomerular damage was attenuated in AAV-shRIG-I mice. Therefore, the effects of ApoL1 on glomerular damage may be, at least partially, through inducing abnormal expression of inflammatory molecules, which may have important implications for treatment of kidney diseases.

New model for explaining the over-response phenomenon in percentage of depth dose curve measured using inorganic scintillating materials for optical fiber radiation sensors.

Inorganic scintillating material used in optical fibre sensors (OFS) when used as dosimeters for measuring percentage depth dose (PDD) characteristics have exhibited significant differences when compared to those measured using an ionization chamber (IC), which is the clinical gold standard for quality assurance (QA) assessments. The percentage difference between the two measurements is as high as 16.5% for a 10 × 10 cm2 field at 10 cm depth below the surface. Two reasons have been suggested for this: the presence of an energy effect and Cerenkov radiation. These two factors are analysed in detail and evaluated quantitatively. It is established that the influence of the energy effect is only a maximum of 2.5% difference for a beam size 10 × 10 cm2 compared with the measured ionization chamber values. And the influence of the Cerenkov radiation is less than 0.14% in an inorganic scintillating material in the case of OFS when using Gd2O2S:Tb as the luminescent material. Therefore, there must be other mechanisms leading to over-response. The luminescence mechanism of inorganic scintillating material is theoretically analysed and a new model is proposed and validated that helps explain the over-response phenomenon.

CAR-T bridging to allo-HSCT as a treatment strategy for relapsed adult acute B-lymphoblastic leukemia: a case report.

BACKGROUND: Adults with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis, especially in patients who relapsed within 6 months of complete remission 1 (CR1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice. However, this can only be considered after complete remission 2 (CR2) is achieved. Therefore, bridging treatment is urgently needed. CASE PRESENTATION: In the present study, we report a relapsed adult B-cell ALL case that achieved CR2 after treatment with CD19-directed chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy. After subsequent allo-HSCT, the patient acquired 21 months of disease-free survival. CONCLUSION: The present results confirm that both CAR-T and allo-HSCT are effective for treating refractory or relapsed B-ALL. However, a novel sequential treatment strategy with these two therapeutic methods may achieve longer disease-free survival time.

Efficacy and safety of recombinant human adenovirus p53 combined with chemoradiotherapy in the treatment of recurrent nasopharyngeal carcinoma.

This study aims to explore the efficacy and safety of recombinant human adenovirus p53 (rAd-p53) combined with chemoradiotherapy (CRT) in the treatment of recurrent nasopharyngeal carcinoma (NPC). A total of 162 recurrent NPC patients were selected and divided randomly into the rAd-p53+CRT, CRT, and rAd-p53 groups. An electrochemical luminescence immune analyzer was used to detect serum levels of tumor markers (carcinoembryonic antigen, cancer antigen 199, and cancer antigen 153). Efficacy evaluation was in accordance with Response Evaluation Criteria in Solid Tumor. Toxicity evaluation was performed according to the WHO grading standard. A 3-year follow-up was performed. A Kaplan-Meier curve was drawn to calculate progression-free survival and the 3-year survival rate. The complete response rate and effective rate (complete response+partial response) of recurrent NPC patients in the rAd-p53+CRT group were higher than those in the CRT and rAd-p53groups. After treatment, compared with the CRT and rAd-p53 groups, the rAd-p53+CRT group had lower serum levels of carcinoembryonic antigen, cancer antigen 199, and cancer antigen 153. The incidences of leukopenia and oral mucositis in the rAd-p53+CRT group were lower than those in the CRT group, but no differences were found between the rAd-p53+CRT and rAd-p53 groups. The progression-free survival and 3-year survival rate of recurrent NPC patients in the rAd-p53+CRT group were higher than the than those in the CRT and rAd-p53 groups. Our study supports that rAd-p53 combined with CRT may provide better efficacy and lower toxicity than rAd-p53 or CRT alone for the treatment of recurrent NPC patients.

[Recent progress of potential effects and mechanisms of chlorogenic acid and its intestinal metabolites on central nervous system diseases].

Chlorogenic acid displays several important roles in the therapeutic properties of many herbs, such as antioxidant activity, antibacterial, antiviral, scavenging free radicals and exciting central nervous system. Only about one-third of chlorogenic acid was absorbed in its prototype, therefore, its gut metabolites play a more important role in the therapeutic properties of chlorogenic acid. It is necessary to consider not only the bioactivities of chlorogenic acid but also its gut metabolites. This review focuses on the potential activities and mechanisms of chlorogenic acid and its gut metabolites on central nervous system diseases.

SENP1 exacerbates acute myeloid leukemia by enhancing BECN1-dependent autophagy through PTBP1 deSUMOylation.

Genetic association between SUMO-specific protease 1 (SENP1) and acute myeloid leukemia (AML) has been validated. However, the mechanism by which SENP1 affects AML proliferation, apoptosis, and autophagy remains unknown. The levels of SENP1 and polypyrimidine tract-binding protein 1 (PTBP1) were measured in AML patients, AML cell lines, and xenograft tissues. The effects of SENP1 on AML proliferation, apoptosis, and BECN1-dependent autophagy were assessed through in vitro and in vivo loss- or gain-of-function experiments. SUMOylation analysis using immunoprecipitation (IP), RNA pull-down, RIP, and RNA stability assays were used to explore the molecular mechanism of SENP1 in AML development. The SENP1 level was elevated in AML samples. Silencing SENP1 impeded the development of AML, as evidenced by the inhibition of proliferation and promotion of G1 phase arrest and apoptosis resulting from SENP1 depletion in AML cells. Moreover, silencing of SENP1 restrained BECN1-depentent autophagy in AML cells. In addition, the overexpression of BECN1 or PTBP1 partially neutralized the effect of SENP1 knockdown on AML cell behavior. Mechanistically, SENP1 mediated PTBP1 deSUMOylation, which then directly interacted with BECN1 mRNA and enhanced its stability. In vivo experiments further confirmed the repressive effects of SENP1 suppression on AML development. Collectively, the SENP1/PTBP1/BECN1 signaling axis has been identified as a significant therapeutic target for enhancing AML treatment.

Newer combination treatments for breast cancer coexisting with acute myeloid leukemia in the novel regimens era: A case report and literature review.

The occurrence of acute myeloid leukemia (AML) with a simultaneous diagnosis of breast cancer (BC) is rarely reported in the literature. The present study reports the case of a 50-year-old female patient diagnosed with AML coexisting with metastatic BC. Following one cycle of treatment with azacytidine in combination with oral venetoclax for AML, the patient achieved complete remission with incomplete hematological recovery. In addition, the mass in the left breast was smaller following adjuvant chemotherapy. However, due to a refusal from the patient to accept an allogeneic hematopoietic stem cell transplantation (allo-HSCT), the patient succumbed 3 months after diagnosis due to septic shock from neutropenia following the third cycle of chemotherapy. Altogether, the present case report highlighted the application of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, both in hematologic malignancies and solid neoplasms, as an effective therapeutic regimen. Considering the fatality rate associated with AML, allo-HSCT is the only available strategy that can be used to achieve the long-term survival of patients with AML and BC.

PTBP1 is a potential indicator of disease progression in acute myeloid leukemia.

This study aimed to verify a novel potential indicator of disease progression in acute myeloid leukemia (AML) patients. Bone marrow samples were collected from 27 AML patients and 27 controls without hematological malignancies. Polypyrimidine tract-binding protein 1 (PTBP1) expression in bone marrow samples was measured, and the association of PTBP1 with the French-American-British (FAB) classification, cytogenetics, risk stratification, and complete remission (CR) rate was analyzed. The correlation between PTBP1 and Ki-67/p53 expression in AML patients was ultimately evaluated. The results showed that PTBP1 mRNA and protein levels were greater in AML patients than in controls. PTBP1 expression was able to distinguish between AML patients and controls (area under the curve, 0.8601; 95% confidence interval, 0.7632-0.9570). Furthermore, PTBP1 expression was associated with an increased frequency of internal tandem duplication mutations within FMS-like tyrosine kinase-3 (FLT3) and a complex karyotype, while PTBP1 expression was not correlated with FAB classification, monosomal karyotype, isolated biallelic CCAAT/enhancer-binding protein α (CEBPA) mutation, or nucleophosmin 1 (NPM1) mutation in patients with AML. Moreover, PTBP1 expression was associated with a poorer prognosis according to risk stratification and a lower CR rate in AML patients. In addition, PTBP1 expression was positively correlated with the expression of the proliferation marker Ki-67 and negatively correlated with the expression of the apoptosis marker p53 in AML patients. Overall, PTBP1 is a viable biomarker that contributes to the risk prediction and the determination of potential drug targets for AML.

Enhancing the stability of mung bean-based milk: Insights from protein characteristics and raw material selection.

Plant-based milk (PBM) alternatives are gaining popularity worldwide as the change of consumers' nutritional habits and health attitudes. Mung beans, recognized for their nutritional value, have gained attention as potential ingredients for PBM. Nevertheless, mung bean-based milk (MBM) faces instability issues common to other plant-based milks. This study investigated the factors influencing MBM stability focusing on raw materials. We selected 6 out of 20 varieties based on their MBM centrifugation sedimentation rates, representing both stable and unstable MBM. Stable MBM exhibited distinct advantages, including reduced separation rate, smaller particle size, lower viscosity, fewer protein aggregates, higher soluble protein content, and increased consumer acceptance. Major nutritional components such as protein, starch, and lipids were not significant different between stable and unstable MBM varieties. The pivotal distinction may lay in the protein properties and composition. Stable MBM varieties exhibited significantly improved protein solubility and emulsion stability, along with elevated concentrations of legume-like acidic subunits, basic 7S proteins, and 28 kDa and 26 kDa vicilin-like subunits. The increasement of these proteins likely contributed to the improvement in protein characteristics that affect MBM stability. These findings offer valuable insights for raw material selection and guidance for future mung bean breeding to enhance mung bean milk production.

Identification of Dalbergiae Odoriferae Lignum active ingredients and potential mechanisms in the treatment of adriamycin-induced cardiotoxicity based on network pharmacology and experimental verification.

The purpose of this study is to investigate the ingredients and mechanisms through which Dalbergiae Odoriferae Lignum (DOL) reduces adriamycin-induced cardiotoxicity. DOL's ingredients and drug targets were acquired from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and adriamycin-induced cardiotoxicity disease targets were gathered from GeneCards and National Center for Biotechnology Information (NCBI). The therapeutic targets of DOL against adriamycin-induced cardiotoxicity were identified by intersecting drug and disease targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using R. Subsequently, core targets were determined and used for molecular docking with DOL ingredients. In vitro and in vivo experiments validated DOL's primary ingredients against adriamycin-induced cardiotoxicity efficacy. Western blot and immunohistochemistry verified its impact on target protein. After intersecting 530 drug targets and 51 disease targets, 19 therapeutic targets for DOL alleviated adriamycin-induced cardiotoxicity were received. Molecular docking demonstrated that DOL primary ingredient formononetin had a robust binding affinity for nitric oxide synthase 3 (NOS3). Experimental results showed that formononetin effectively mitigated adriamycin-induced cardiotoxicity. Additionally, western blot and immunohistochemistry showed that formononetin improved NOS3 expression. The network pharmacology and experimentation suggest that the primary ingredient of DOL, formononetin, may target NOS3 to act as a therapeutic agent for adriamycin-induced cardiotoxicity.

Downregulation of autophagy is associated with poor clinical outcome after immunochemotherapy in patients with diffuse large B-cell lymphoma.

This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL and patients with reactive lymphoproliferative disease (RLD) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in RLD patients compared with those with DLBCL, but the difference was not statistically significant (p > 0.05). p62 levels in DLBCL patients were significantly higher than those in RLD patients (p < 0.05). Beclin-1 expression was associated only with the Ann Arbor stage (p < 0.05), whereas p62 expression was associated with the Ann Arbor stage, IPI score, extranodal involvement, and Ki-67 index (p < 0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in DLBCL patients. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (p > 0.05). However, high p62 expression in DLBCL patients was associated with reduced 2-year PFS compared with that of patients with low p62 expression (p < 0.05); the 2-year OS was not affected (p > 0.05). Our results demonstrate that autophagic activity affects the prognosis of DLBCL patients; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of DLBCL patients.

Elevated expression of hyaluronic acid binding protein 1 (HABP1)/P32/C1QBP is a novel indicator for lymph node and peritoneal metastasis of epithelial ovarian cancer patients.

The present study aims to clarify whether hyaluronan binding protein 1 (HABP1/p32/C1QBP) is an indicator of peritoneal and lymph node metastasis in epithelial ovarian cancer (EOC), which to the authors' knowledge is not previously reported by others. Western blot analysis demonstrated that HABP1 was highly overexpressed in most metastatic lesions. Of 89 patients whose primary tumors showed high HABP1 expression on immunohistochemical staining, 85 (95.5%) presented peritoneal metastases and 43 (48.3%) had lymph node metastases. Univariate and multivariate logistic regression analyses revealed that HABP1 overexpression correlated with peritoneal dissemination and lymph node metastasis in EOC. The specificity and positive predictive value of HABP1 staining were shown to be better for peritoneal metastasis, while the negative and sensitivity predictive value of HABP1 staining were better for lymph node metastasis. The odds ratio of high versus low staining for peritoneal spread was 9.236 (95% confidence interval (CI), 2.705, 19.316), and that for lymph node metastasis was 8.614 (95% CI, 2.507, 21.039). Furthermore, HABP1 protein may potentially be used alone or in combination with other markers as a predictive marker of EOC patients with lymph node metastasis and/or peritoneal dissemination.

Changes in glycosylated proteins in colostrum and mature milk and their implication.

Introduction: Glycosylation is one of the essential post-translational modifications that influences the function of milk proteins. Methods: In the present study, 998 proteins and 764 glycosylated sites from 402 glycoproteins were identified in human milk by TMT labeling proteomics. Compared to human milk proteins, the glycoproteins were mainly enriched in cell adhesion, proteolysis, and defense/immune process. Results: The abundance of 353 glycosylated sites and their 179 parent proteins was quantified. After normalization to their parent protein's abundance, 78 glycosylated sites in 56 glycoproteins and 10 glycosylated sites in 10 glycoproteins were significantly higher in colostrum and mature milk, respectively. These changed glycoproteins were mainly related to host defense. Intriguingly, one glycosylated site (Asp144) in IgA and two glycosylated sites (Asp38 and Asp1079) in tenascin are significantly upregulated even though their protein abundance was downregulated during lactation. Discussion: This study helps us figure out the critical glycosylated sites in proteins that might influence their biological function in an unbiased way.