sCD155 as a potential marker for diagnosing the vascular invasion in hepatic alveolar echinococcosis.

BACKGROUND: Alveolar Echinococcosis (AE) is a malignant zoonotic disease caused by Echinococcus multilocularis infection. Considering whether the lesion is accompanied by vascular invasion (VI) is crucial for treatment strategies. A cost-effective and convenient clinical diagnostic method is urgently needed to supplement current techniques. Consequently, we detected soluble CD155 (sCD155) as a potential biomarker for diagnosing VI in hepatic alveolar echinococcosis (HAE). METHODS: Blood samples were from 42 AE patients and 49 healthy controls (HCs). Based on the computed tomography (CT) and contrast-enhanced CT, AE patients were further categorized into HAE with VI (VIAE; 27 cases) and HAE without VI (NVAE; 15 cases). The sCD155 concentration was measured by an enzyme-linked immunosorbent assay (ELISA). Correlations between sCD155 expression levels and clinicopathological features of AE patients were analyzed using SPSS and GraphPad Prism software. RESULTS: The sCD155 concentrations in AE patients were significantly higher than in HCs. The serum sCD155 level significantly differed between the VIAE and NVAE groups. The univariate analysis showed that VI of AE was significantly correlated with the sCD155 level when the sCD155 was greater than 11 ng/mL. After adjusting for potential confounding factors, the multivariable analysis showed that sCD155 had an independent effect on VI of HAE. The receiver operating characteristic (ROC) curve showed that sCD155 could differentially diagnose VI of HAE at the cut-off value of 11.08 ng/mL with an area under the curve (AUC) value of 0.75. The sensitivity and specificity were 74.07 % and 66.67 %, respectively; the positive and negative predictive values were 74.07 % and 60.00 %, respectively. CONCLUSION: The sCD155 could be a VI biomarker for HAE. Elevated sCD155 levels are indicative of an increased likelihood of concomitant VI in HAE patients, necessitating a thorough evaluation of vascular impairment and the formulation of individualized management strategies.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

Pharmacological approaches for targeting lysosomes to induce ferroptotic cell death in cancer.

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.

Inhibition of AMPK activation in Echinococcus granulosus sensu stricto limits the parasite's glucose metabolism and survival.

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, ß, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism in E. granulosus s.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of E. granulosus sensu stricto (s.s.) and disrupted the ultrastructure. The results of in vivo experiments showed that the AMPK inhibitor had a significant therapeutic effect on E. granulosus s.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions in E. granulosus s.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.

Machine learning-assisted serum SERS strategy for rapid and non-invasive screening of early cystic echinococcosis.

Early and accurate diagnosis of cystic echinococcosis (CE) with existing technologies is still challenging. Herein, we proposed a novel strategy based on the combination of label-free serum surface-enhanced Raman scattering (SERS) spectroscopy and machine learning for rapid and non-invasive diagnosis of early-stage CE. Specifically, by establishing early- and middle-stage mouse models, the corresponding CE-infected and normal control serum samples were collected, and silver nanoparticles (AgNPs) were utilized as the substrate to obtain SERS spectra. The early- and middle-stage discriminant models were developed using a support vector machine, with diagnostic accuracies of 91.7% and 95.7%, respectively. Furthermore, by analyzing the serum SERS spectra, some biomarkers that may be related to early CE were found, including purine metabolites and protein-related amide bands, which was consistent with other biochemical studies. Thus, our findings indicate that label-free serum SERS analysis is a potential early-stage CE detection method that is promising for clinical translation.

Rapid and non-invasive detection of cystic echinococcosis in sheep based on serum fluorescence spectrum combined with machine learning algorithms.

Cystic echinococcosis (CE) is a grievous zoonotic parasitic disease. Currently, the traditional technology of screening CE is laborious and expensive, developing an innovative technology is urgent. In this study, we combined serum fluorescence spectroscopy with machine learning algorithms to develop an innovative screening technique to diagnose CE in sheep. Serum fluorescence spectra of Echinococcus granulosus sensu stricto-infected group (n = 63) and uninfected E. granulosus s.s. group (n = 60) under excitation at 405 nm were recorded. The linear support vector machine (Linear SVM), Quadratic SVM, medium radial basis function (RBF) SVM, K-nearest neighbor (KNN), and principal component analysis-linear discriminant analysis (PCA-LDA) were used to analyze the spectra data. The results showed that Quadratic SVM had the great classification capacity, its sensitivity, specificity, and accuracy were 85.0%, 93.8%, and 88.9%, respectively. In short, serum fluorescence spectroscopy combined with Quadratic SVM algorithm has great potential in the innovative diagnosis of CE in sheep.

Effects of Subcostal Anterior Quadratus Lumborum Block with and without Dexmedetomidine on Postoperative Rehabilitation in Patients Undergoing Laparoscopic Renal Surgery: A Prospective Double-Blinded Randomized Controlled Study.

Background: The combination of different anesthesia techniques or adjuvant drugs can relieve the stress response to surgery, reduce adverse reactions and improve the clinical outcome. We investigated the effects of subcostal anterior quadratus lumborum block (SQLB) with and without dexmedetomidine (DEX) on postoperative rehabilitation for laparoscopic renal surgery (LRS). Methods: We included 90 patients in this single-center study. All were scheduled for elective laparoscopic radical or partial nephrectomy under general anesthesia (GA). We randomly and evenly assigned them to three groups: Group GA (GA alone), Group QG (SQLB with 30 mL of 0.25% ropivacaine and GA), and Group DQG (SQLB with 30 mL of 0.25% ropivacaine plus 1 µg/kg DEX and GA). The primary outcomes were serum creatinine (Cr) and blood urea nitrogen (BUN) levels; the secondary outcomes included the average numeric rating scale (NRS) scores at rest and during activity within 48 h postoperatively; perioperative opioid consumption; the time to first ambulation, exhaust, and fluid intake, and postoperative adverse reactions. Results: The serum Cr and BUN levels in Group DQG decreased significantly compared with Group GA (P < 0.05). The average NRS scores in Group DQG were significantly lower than other two groups (P < 0.05). Furthermore, the indexes reduced significantly in Group QG compared with Group GA (P < 0.05). Groups DQG and QG had lower consumption of opioid compared with Group GA (P < 0.05). The recovery indicators in Groups DQG and QG were higher quality than Group GA (P < 0.05). The incidences of adverse reactions in Group DQG was significantly lower than the other groups (P < 0.05). Conclusion: SQLB with and without DEX could attenuate postoperative pain, reduce opioids requirement and side effects, as well as facilitate postoperative early rehabilitation. More interesting, SQLB with DEX could confer kidney protection. Clinical Trial Registration Number: The Chinese Clinical Trial Registry (ChiCTR2200061554).

Andrographolide causes p53-independent HCC cell death through p62 accumulation and impaired DNA damage repair.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly lethal cancer characterized by dominant driver mutations, including p53. Consequently, there is an urgent need to search for novel therapeutic agents to treat HCC. Andrographolide (Andro), a clinically available anti-inflammatory phytochemical agent, has shown inhibitory effects against various types of cancer, including HCC. However, the underlying molecular mechanisms of its action remain poorly understood. PURPOSE: This study aims to investigate the molecular mechanisms by which p53 and p62 collectively affect Andro-induced HCC cell death, using both in vitro and in vivo models. METHODS: In vitro cellular experiments were conducted to examine the effects of Andro on cell viability and elucidate its mechanisms of action. In vivo xenograft experiments further validated the anti-cancer effects of Andro. RESULTS: Andro induced dose- and time-dependent HCC cell death while sparing normal HL-7702 hepatocytes. Furthermore, Andro caused DNA damage through the generation of reactive oxygen species (ROS), a critical event leading to cell death. Notably, HCC cells expressing p53 exhibited greater resistance to Andro-induced cell death compared to p53-deficient cells, likely due to the ability of p53 to induce G2/M cell cycle arrest. Additionally, Andro-induced p62 aggregation led to the proteasomal degradation of RAD51 and 53BP1, two key proteins involved in DNA damage repair. Consequently, silencing or knocking out p62 facilitated DNA damage repair and protected HCC cells. Importantly, disruption of either p53 or p62 did not affect the expression of the other protein. These findings were further supported by the observation that xenograft tumors formed by p62-knockout HCC cells displayed increased resistance to Andro treatment. CONCLUSION: This study elucidates the mechanistic basis of Andro-induced HCC cell death. It provides valuable insights for repurposing Andro for the treatment of HCC, regardless of the presence of functional p53.

Glycopolymer-grafted nanoparticles as glycosaminoglycan mimics with cell proliferation and anti-tumor metastasis activities.

Glycosaminoglycans (GAGs) are naturally existing extracellular components with a variety important biological functions. However, their heterogeneous chemical compositions and the challenges in purification have become the main disadvantages for clinical applications. Thus, various synthetic glycopolymers have been designed to mimic the structures and functions of natural GAGs. In the current study, glycopolymers from structurally simple glucose or N-acetylglucosamine monomers were synthesized, which were further subjected to sulfation of different degrees and grafting onto silica nanoparticles, leading to spherical-shaped nano-structures of uniform diameters. With the successively strengthened multivalent effect, the obtained glycopolymer nanoparticles not only showed excellent effects on promotion of cell proliferation by stabilizing growth factors, but also significantly inhibited tumor metastasis by weakening the adhesion between tumor cells and activated platelets. Among the prepared nanoparticles, S3-PGNAc@Si with N-acetylglucosamine segment and the highest sulfation degree exhibited the strongest bioactivities, which were even close to those of heparin. This work presents a novel approach for structural and functional mimicking of natural GAGs from simple and low-cost monosaccharides, holding great potential for a range of biomedical applications.

In vitro and in vivo Efficacies of Novel Harmine Derivatives in the Treatment of Cystic Echinococcosis.

Introduction: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the larvae of the Echinococcus granulosus sensu lato (s.l.) cluster. The current existing drugs have limited therapeutic efficacy against cystic echinococcosis, and thus, there is an urgent need to develop new drugs. Methods: In this study, 7 harmine (HM) derivatives were screened and the effects of HM derivatives on E. granulosus sensu stricto (s.s.) were evaluated by in vitro and mouse experiments. The safety of the HM derivatives was assessed by cytotoxicity assays, acute toxicity study in animals and subacute toxicity study. Results: These results show that the HM derivatives H-2-168 and DH-004 exhibited more significant antiparasitic effects at an initial concentration of 40 µM. The results of further studies showed that H-2-168 and DH-004 had dose-dependent effects against protoscoleces and had satisfactory therapeutic outcomes in vivo. Electron microscopy observations demonstrated that H-2-168 and DH-004 caused severe disruption of the parasite ultrastructure. Notably, the results of the acute toxicity and subchronic toxicity studies showed that H-2-168 and DH-004 had significantly improved safety. In addition, we found that H-2-168 and DH-004 induced DNA damage in E. granulosus s.s., which may be the mechanism by which these drugs produce their therapeutic effects. Discussion: Overall, the data from this work demonstrate that H-2-168 and DH-004 are highly effective candidate compounds with low toxicity for the treatment of CE and will provide a new therapeutic strategy for CE pharmacological treatment.

A nonclassically secreted effector of Magnaporthe oryzae targets host nuclei and plays important roles in fungal growth and plant infection.

Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases and poses a growing threat to food security worldwide. Like many other filamentous pathogens, rice blast fungus releases multiple types of effector proteins to facilitate fungal infection and modulate host defence responses. However, most of the characterized effectors contain an N-terminal signal peptide. Here, we report the results of the functional characterization of a nonclassically secreted nuclear targeting effector in M. oryzae (MoNte1). MoNte1 has no signal peptide, but can be secreted and translocated into plant nuclei driven by a nuclear targeting peptide. It could also induce hypersensitive cell death when transiently expressed in Nicotiana benthamiana. Deletion of the MoNTE1 gene caused a significant reduction of fungal growth and conidiogenesis, partially impaired appressorium formation and host colonization, and also dramatically attenuated the pathogenicity. Taken together, these findings reveal a novel effector secretion pathway and deepen our understanding of rice-M. oryzae interactions.

Preoperative Ultrasound-Guided Internal Branch Block of Superior Laryngeal Nerve Reduces Postoperative Sore Throat Caused by Double Lumen Endotracheal Intubation: A Randomized Trial.

BACKGROUND: Postoperative sore throat (POST) is one of the more common side effects of tracheal intubation patients under general anesthesia (GA) after extubation using double-lumen endobronchial tubes (DLTs). The internal branches of the superior laryngeal nerve (SLN) block (iSLNB) have been reported to anesthetize the larynx for airway manipulation (such as awake tracheal intubation) and pain treatment efficiently. We hypothesized that ultrasound-guided iSLNB (US-guided iSLNB) combined with GA would ameliorate the incidence and severity of POST and hoarseness. METHODS: Patients (n = 82) undergoing thoracoscopic resection of pulmonary nodules/lobes/segments with one-lung ventilation (OLV) under GA were randomized into 2 groups depending on whether performed with iSLNB (S group, n = 41) or not (C group, n = 41) under GA. Patients in the S group received US-guided iSLNB bilaterally before surgery. POST and hoarseness were assessed at 2, 6, and 24 hours after surgery. The primary outcome of this study was the incidence of POST at 6 hours after surgery between groups. RESULTS: The overall accumulated incidence of POST was lower in the S goup than in the C group (9/41 vs 20/41; 95% CI, 0.30 [0.11-0.77]; P = .011). The incidence and severity of POST was lower in the S group than in the C group at 2 hours (9/41 vs 20/41; 95% CI, 0.30 [0.11-0.77]; P = .008 and P = .004) and 6 hours after (7/41 vs 17/41; 95% CI, 0.29 [0.10-0.81]; P = .012 and P = .015) surgery. The incidence and severity of POST at 24 hours after surgery was nonsignificant. However, the incidence and severity of hoarseness was comparable between the 2 groups at 2, 6, and 24 hours after surgery. CONCLUSIONS: Preoperative US-guided iSLNB could significantly ameliorate the incidence and severity of POST induced by double-lumen bronchial catheter intubation.

Label-free surface-enhanced Raman spectroscopy of serum with machine-learning algorithms for gallbladder cancer diagnosis.

Gallbladder cancer (GBC) is a rare but frequently fatal biliary tract malignancy that is typically discovered when it is already advanced. In this study, we investigated a novel technique for the quick and non-invasive diagnosis of GBC based on serum surface-enhanced Raman spectroscopy (SERS). SERS spectra of serum from 41 patients with GBC and 72 normal subjects were recorded. Principal component analysis-linear discriminant analysis (PCA-LDA), and PCA-support vector machine (PCA-SVM), Linear SVM and Gaussian radial basis function-SVM (RBF-SVM) algorithms were used to establish the classification models, respectively. When the Linear SVM was used, the overall diagnostic accuracy for classifying the two groups could achieve 97.1%, and when RBF-SVM was used, the diagnostic sensitivity of GBC was 100%. The results demonstrated that SERS combination with a machine learning algorithm is a promising candidate to be one of the diagnostic tools for GBC in the future.

Rapid detection of serological biomarkers in gallbladder carcinoma using fourier transform infrared spectroscopy combined with machine learning.

Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. GBC is difficult to diagnose and treat at an early stage because of the lack of effective serum markers and typical symptoms, resulting in low survival rates. This study aimed to investigate the applicability of dried serum Fourier-transform infrared (FTIR) spectroscopy combined with machine learning algorithms to correctly differentiate patients with GBC from patients with gallbladder disease (GBD), cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC) and healthy individuals. The differentiation between healthy individuals and GBC serum was better using principal component analysis (PCA) and linear discriminant analysis (LDA) for six spectral regions, especially in the protein (1710-1475 cm-1) and combined (1710-1475 + 1354-980 cm-1) region. However, the PCA-LDA model poorly differentiated GBC from GBD, CCA, and HCC in serum spectra. We evaluated the PCA- LDA, PCA-support vector machine (SVM), and radial basis kernel function support vector machine (RBF-SVM) models for GBC diagnosis and found that the RBF-SVM model performed the best, with 88.24-95% accuracy, 95.83% sensitivity, and 78.38-94.44% specificity in the 1710-1475 + 1354-980 cm-1 region. This study demonstrated that serum FTIR spectroscopy combined with the RBF-SVM algorithm has great clinical potential for GBC screening.

Rapid Identification of Benign Gallbladder Diseases Using Serum Surface-Enhanced Raman Spectroscopy Combined with Multivariate Statistical Analysis.

In this study, we looked at the viability of utilizing serum to differentiate between gallbladder (GB) stones and GB polyps using Surface-enhanced Raman spectroscopy (SERS), which has the potential to be a quick and accurate means of diagnosing benign GB diseases. Rapid and label-free SERS was used to conduct the tests on 148 serum samples, which included those from 51 patients with GB stones, 25 patients with GB polyps and 72 healthy persons. We used an Ag colloid as a Raman spectrum enhancement substrate. In addition, we employed orthogonal partial least squares discriminant analysis (OPLS-DA) and principal component linear discriminant analysis (PCA-LDA) to compare and diagnose the serum SERS spectra of GB stones and GB polyps. The diagnostic results showed that the sensitivity, specificity, and area under curve (AUC) values of the GB stones and GB polyps based on OPLS-DA algorithm reached 90.2%, 97.2%, 0.995 and 92.0%, 100%, 0.995, respectively. This study demonstrated an accurate and rapid means of combining serum SERS spectra with OPLS-DA to identify GB stones and GB polyps.

Downregulation of LncRNA GCLC-1 Promotes Microcystin-LR-Induced Malignant Transformation of Human Liver Cells by Regulating GCLC Expression.

Microcystin-LR (MCLR) is an aquatic toxin, which could lead to the development of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are considered important regulatory elements in the occurrence and development of cancer. However, the roles and mechanisms of lncRNAs during the process of HCC, induced by MCLR, remain elusive. Here, we identified a novel lncRNA, namely lnc-GCLC-1 (lncGCLC), which is in close proximity to the chromosome location of glutamate-cysteine ligase catalytic subunit (GCLC). We then investigated the role of lncGCLC in MCLR-induced malignant transformation of WRL68, a human hepatic cell line. During MCLR-induced cell transformation, the expression of lncGCLC and GCLC decreased continuously, accompanied with a consistently high expression of miR-122-5p. Knockdown of lncGCLC promoted cell proliferation, migration and invasion, but reduced cell apoptosis. A xenograft nude mouse model demonstrated that knockdown of lncGCLC promoted tumor growth. Furthermore, knockdown of lncGCLC significantly upregulated miR-122-5p expression, suppressed GCLC expression and GSH levels, and enhanced oxidative DNA damages. More importantly, the expression of lncGCLC in human HCC tissues was significantly downregulated in the high-microcystin exposure group, and positively associated with GCLC level in HCC tissues. Together, these findings suggest that lncGCLC plays an anti-oncogenic role in MCLR-induced malignant transformation by regulating GCLC expression.

Rapid and accurate screening of cystic echinococcosis in sheep based on serum Fourier-transform infrared spectroscopy combined with machine learning algorithms.

Cystic echinococcosis (CE) in sheep is a serious zoonotic parasitic disease caused by Echinococcus granulosus sensu stricto (s.s.). Presently, the screening technology for CE in sheep is time-consuming and inaccurate, and novel screening technology is urgently needed. In this work, we combined machine-learning algorithms with Fourier transform infrared (FT-IR) spectroscopy of serum to establish a quick and accurate screening approach for CE in sheep. Serum samples from 77 E. granulosus s.s.-infected sheep to 121 healthy control sheep were measured by FT-IR spectrometer. To optimize the classification accuracy of the serum FI-TR method for the E. granulosus s.s.-infected sheep and healthy control sheep, principal component analysis (PCA), linear discriminant analysis, and support vector machine (SVM) algorithms were used to analyze the data. Among all the bands, 1500-1700 cm-1 band has the best classification effect; its diagnostic sensitivity, specificity, and accuracy of PCA-SVM were 100%, 95.74%, and 96.66%, respectively. The study showed that serum FT-IR spectroscopy combined with machine learning algorithms has great potential for rapid and accurate screening methods for the CE in sheep.

Targeting mitophagy as a novel therapeutic approach in liver cancer.

Ischemia may be the most common pathological occurrence to restrict nutrient availability and induce macroautophagy/autophagy. As a self-digestive process, autophagy helps sustain nutrient/energy and restrict damages in short-term scenarios, but it switches to a self-destructive process leading to cell death in long-term scenarios. Notably, ischemia has been used as one clinical application to treat cancer, particularly transarterial embolization (TAE) and chemoembolization (TACE) as the first-line treatments of intermediate-stage hepatocellular carcinoma (HCC, the predominant type of liver cancer). Partly due to the induced autophagy together with hypoxia-induced angiogenesis, TAE/TACE is not successful to treat HCC in many cases. Our recent work demonstrated that simultaneous treatments with sorafenib (a first-line therapeutic agent for advanced HCC) can sensitize HCC cells to cell death induced by glucose starvation via impairing mitophagy, a mitochondria-specific form of autophagy. Moreover, we identified SIAH1 as an important E3 ubiquitin ligase for mitophagic induction in HCC cells.

Subcutaneous infection mouse model could be applied into real time monitoring the efficacy of anti-cystic echinococcosis drug in vivo.

Cystic echinococcosis (CE) is a zoonotic parasitic disease with a cosmopolitan distribution, and it is urgent to develop novel anti-helminthic agents. The intraperitoneal (ip) infection mice model was widely used to evaluate the efficacy of potential anti-CE compounds. Still, it's time-consuming, and the inability to achieve real-time monitoring hinders the development of potential anti-CE compounds. In this study, a CE mouse model was established by subcutaneous (sc) injection of protoscoleces of Echinococcus granulosus sensu stricto (E.granulosus s.s.) and used to assess the efficiency and efficacy of prospective anti-CE drugs. Compared to the ip infection CE mice model, the lesion volume of sc infection protoscoleces of E.granulosus s.s. (EgPSCs) could be measured by vernier caliper at week 6 post-infection. In contrast, the lesion volume of ip infection CE mice model was detected by ultrasound-assisted diagnosis at week 16 post-infection. Oral administration of albendazole (ABZ) could reduce cystic weight by 32.17% and 17.61%, the cystic number by 12.24% and 25.19%, and damage the ultrastructure of the cysts of E. granulosus s.s. in the sc and ip infection group, respectively. Furthermore, we found that the sc infection mice model could real-time monitor the lesion volume of E. granulosus s.s. during the ABZ and everolimus treatment. Therefore, we consider that the sc infection CE mice model is an assistant tool for screening and developing potential anti-CE compounds.

Upregulated TUBG1 expression is correlated with poor prognosis in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) development is a complex pathological process. Tubulin gamma 1 (TUBG1) plays an oncogenic role in several human cancers; however, its functional role in HCC tumorigenesis remains unknown. Methods: Herein we first evaluated the gene expression levels of TUBG1 in HCC using data from The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases. We then elucidated the association between TUBG1 gene expression levels and survival rates of patients with HCC. Cell cycle, proliferation, transwell migration, and matrigel invasion assays were used to study the effects of TUBG1 on the malignant phenotypes of HCC cells. Results: Based on the data obtained from the aforementioned databases and our in vitro experiments, TUBG1 was found to be overexpressed in HCC and patients with high TUBG1 expression levels showed a remarkably poor overall survival rate. In addition, the expression of TUBG1 significantly promoted the malignant phenotypes of HCC cells in vitro. Gene ontology term enrichment analysis revealed that co-regulated genes were enriched in biological processes mainly involved in chromosome segregation, chromosomal region, and chromatin binding; moreover, Kyoto Encyclopedia of Genes and Genome pathway analysis showed that they were mainly involved in cell cycle, oocyte meiosis, platinum drug resistance, and the p53 signaling pathway. Conclusions: We report that TUBG1 is an important oncogene in HCC. It promotes HCC progression and may serve as a potential prognostic biomarker for HCC. Future studies are warranted to unveil molecular biological mechanisms underlying TUBG1 carcinogenesis.