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Journal of Traditional Chinese Medicine... Oct 2023The aim of this study was to investigate the protective effects of Tuina (a traditional Chinese massage therapy) on intervertebral disc (IVD) degeneration and the...
Effect of Tuina along "bladder meridian" alleviating intervertebral disc degeneration by regulating the transforming growth factor-β1/Smad signaling pathway in a rabbit model.
OBJECTIVE
The aim of this study was to investigate the protective effects of Tuina (a traditional Chinese massage therapy) on intervertebral disc (IVD) degeneration and the regulatory mechanisms of the transforming growth factor-β1 (TGF-β1)/small mothers against decapentaplegic (Smad) signaling pathway.
METHODS
Thirty New Zealand white rabbits were randomized into five groups: the control group, model group, model + Tuina group (Tuina group), model + TGF-β1 group (TGF-β1 group), and model + TGF-β1 inhibitor SB431542 group (SB431542 group). The model was established by posterolateral annulus fibrosus puncturing (AFP). Recombinant TGF-β1 and inhibitor SB431542 was injected into the TGF-β1 group and SB431542 group with a microsyringe, respectively. The rabbits in the Tuina group received Tuina treatment along the bladder meridian for 4 weeks. Magnetic resonance imaging (MRI) was performed on rabbits before AFP and after 4 weeks of intervention. Lumbar IVDs (L2-L3 to L4-L5) were harvested after intervention. Histopathological changes in the IVDs were measured by hematoxylin and eosin (HE) staining. Type I collagen was analyzed by immunohistochemistry detection. The expression level of matrix metalloproteinase-3 (MMP3) was determined by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated nick end labeling and Western blotting. Real-time polymerase chain reaction and Western blotting were used to analyze the expression of TGF-β1 and Smad2/3/4 and a disintegrin and metalloproteinase with thrombospondin motifs 5.
RESULTS
Posterolateral AFP induced IVD degeneration in rabbits with histopathological damage and noticeable changes in MRI images. Tuina alleviated histo-pathological changes and reversed the expression of extracellular matrix degeneration-related molecules and apoptosis-related proteins. Furthermore, AFP induced the activation of TGF-β1 and Smad2/3/4, whereas Tuina therapy markedly reduced the protein expression of Smad2/3 and the gene expression of TGF-β1 and Smad2/3/4. Additionally, the TGF-β1/Smad signaling pathway was activated in the TGF-β1 group, while the TGF-β1/Smad signaling pathway was inhibited in the SB431542 group.
CONCLUSION
Posterolateral AFP induced disc degeneration as determined by MRI assessment and histological analysis. Tuina alleviated disc degeneration, possibly by inhibiting the fibrotic response mediated by the TGF-β1/Smad pathway, thus alleviating extracellular matrix degeneration and reducing cell apoptosis.
Topics: Rabbits; Animals; Female; Humans; Transforming Growth Factor beta1; Intervertebral Disc Degeneration; Meridians; Mothers; Urinary Bladder; alpha-Fetoproteins; Signal Transduction
PubMed: 37679987
DOI: 10.19852/j.cnki.jtcm.2023.05.005 -
International Journal of Molecular... Dec 2023Hepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however,...
Hepatocellular carcinoma (HCC) is the deadliest malignant tumour worldwide. The metalloproteinase ADAM17 is associated with tumour formation and development; however, its significance in HCC is unclear. This study aimed to investigate the role of ADAM17 in HCC and the correlation between its expression and immune cell infiltration. ADAM17 expression was analysed in pan-cancer and HCC tissues using The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Kaplan-Meier survival analysis displayed a negative association between ADAM17 expression and the overall survival of patients with HCC. High ADAM17 expression was linked to poor tumour/node (T/N) stage and alpha fetoprotein (AFP) levels. Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes analyses revealed the enrichment of several pathways, including epithelial-mesenchymal transition, inflammatory response, Hedgehog, and KRAS signalling, in patients with upregulated ADAM17. ADAM17 was shown to be positively correlated with immune cell infiltration and immune checkpoint expression via the Tumour Immune Estimation Resource (TIMER) database and immunohistochemistry analyses. Protein-protein interaction (PPI) network analysis revealed that ADAM17 plays a core role in cancer development and immune evasion. In vitro and in vivo experiments demonstrated that ADAM17 influences HCC growth and metastasis. In conclusion, ADAM17 is upregulated in most cancers, particularly HCC, and is critical in the development and immune evasion of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Epithelial-Mesenchymal Transition; Signal Transduction; Databases, Factual; ADAM17 Protein
PubMed: 38069391
DOI: 10.3390/ijms242317069 -
RSC Advances Sep 2023It has been reported that organic extracts derived from soft corals belonging to the genus have exhibited a wide range of therapeutic characteristics. Based on...
It has been reported that organic extracts derived from soft corals belonging to the genus have exhibited a wide range of therapeutic characteristics. Based on biochemical and histological techniques, we aimed to assess the hepatoprotective role of the organic extract and its principal steroidal contents derived from the Red Sea soft coral on acetaminophen-induced liver fibrosis in rats. Serum liver function parameters (ALT, AST, ALP and total bilirubin) were quantified using a spectrophotometer, and both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels were determined by using enzyme-linked immunosorbent assay (ELISA) kits while transformed growth factor beta (TGF-β) and tumor necrosis factor α (TNF-α) in liver tissue homogenate were determined using ELISA, and TGF-β and TNF-α gene expression in liver tissue was determined using real-time PCR following extraction and purification. Histopathological alterations in hepatic tissue were also examined under a microscope. In order to prioritize the isolation and characterization of the most promising marine steroids from the organic extract of the Red Sea soft coral as hepatoprotective agents, a computational approach was employed. This approach involved molecular docking (MDock) and analysis of the structure-activity relationship (SAR) against glutathione--transferase (GST) and Cu-Zn human superoxide dismutase (Cu-ZnSOD) enzymes. Although the major role in the detoxification of foreign chemicals and toxic metabolites of GST and SOD enzymes is known, there is a lack of knowledge about the mode of action of the hepatoprotective process and those of the targets involved. The present study investigated the multiple interactions of a series of marine steroids with the GST and SOD enzymes, in order to reveal insights into the process of hepatoprotection.
PubMed: 37711373
DOI: 10.1039/d3ra04843h -
PLoS Neglected Tropical Diseases Jan 2024Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and...
BACKGROUND
Extensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.
METHODS
A comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.
RESULTS
Compared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.
CONCLUSION
HCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.
AUTHOR SUMMARY
Clonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.
Topics: Animals; Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Epithelial Cell Adhesion Molecule; Clonorchiasis; alpha-Fetoproteins; CA-19-9 Antigen; Neoplasm Staging; China; Prognosis; Clonorchis sinensis; Cholangiocarcinoma; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Liver Cirrhosis; Retrospective Studies
PubMed: 38285640
DOI: 10.1371/journal.pntd.0011906 -
European Radiology Nov 2023To develop and validate a risk score based on preoperative clinical-radiological parameters for predicting overall survival (OS) in patients undergoing surgical...
OBJECTIVE
To develop and validate a risk score based on preoperative clinical-radiological parameters for predicting overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma (HCC).
METHODS
From July 2010 to December 2021, consecutive patients with surgically-proven HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled. A preoperative OS risk score was constructed in the training cohort using a Cox regression model and validated in a propensity score-matched internal validation cohort and an external validation cohort.
RESULTS
A total of 520 patients were enrolled, among whom 210, 210, and 100 patients were from the training, internal validation, and external validation cohorts, respectively. Independent predictors for OS included incomplete tumor "capsule," mosaic architecture, tumor multiplicity, and serum alpha-fetoprotein, which were incorporated into the "OSASH score." The C-index the OSASH score was 0.85, 0.81, and 0.62 in the training, internal, and external validation cohorts, respectively. Using 32 as the cutoff point, the OSASH score stratified patients into prognostically distinct low- and high-risk groups among all study cohorts and six subgroups (all p < 0.05). Furthermore, patients with BCLC stage B-C HCC and OSASH-low risk achieved comparable OS to that of patients with BCLC stage 0-A HCC and OSASH-high risk in the internal validation cohort (5-year OS rates, 74.7 vs. 77.8%; p = 0.964).
CONCLUSION
The OSASH score may help predict OS in HCC patients undergoing hepatectomy and identify potential surgical candidates among those with BCLC stage B-C HCC.
CLINICAL RELEVANCE STATEMENT
By incorporating three preoperative MRI features and serum AFP, the OSASH score may help predict postsurgical overall survival in patients with hepatocellular carcinoma and identify potential surgical candidates among those with BCLC stage B and C HCC.
KEY POINTS
• The OSASH score incorporating three MRI features and serum AFP can be used to predict OS in HCC patients who received curative-intent hepatectomy. • The score stratified patients into prognostically distinct low- and high-risk strata in all study cohorts and six subgroups. • Among patients with BCLC stage B and C HCC, the score identified a subgroup of low-risk patients who achieved favorable outcomes after surgery.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; alpha-Fetoproteins; Hepatectomy; Prognosis
PubMed: 37191923
DOI: 10.1007/s00330-023-09725-7 -
IScience Sep 2023To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to...
To gain deeper insights into transcriptomes and epigenomes of organoids, liver organoids from two states (expandable and more differentiated) were subjected to single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) analyses. Mitochondrial gene expression was higher in differentiated than in non-differentiated hepatocytes, with ATAC-seq peaks increasing near the mitochondrial control region. Differentiation of liver organoids resulted in the expression of transcription factors that act as enhancers and repressors. In addition, epigenetic mechanisms regulating the expression of alpha-fetoprotein (AFP) and albumin (ALB) differed in liver organoids and adult liver. Knockdown of PDX1, an essential transcription factor for pancreas development, led to the hepatic maturation of liver organoids through regulation of AFP and ALB expression. This integrative analysis of the transcriptomes and epigenomes of liver organoids at the single-cell level may contribute to a better understanding of the regulatory networks during liver development and the further development of mature human liver models.
PubMed: 37680467
DOI: 10.1016/j.isci.2023.107675 -
Cancer Reports (Hoboken, N.J.) Apr 2024The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving...
AIMS
The aim of the present study was to elucidate detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving atezolizumab plus bevacizumab (Atez/Bev) treatment.
METHODS
A total of 719 patients (males 577, median age 74 years) treated with Atez/Bev between September 2020 and January 2023 were enrolled. Factors related to overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were retrospectively examined, and the prognostic ability of the newly developed system was compared to CRAFITY score using concordance index (c-index) and Akaike information criterion (AIC) results.
RESULTS
Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used to develop the IMmunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring system. For IMABALI-De scores of 0, 1, 2, 3, 4, and 5, OS was not applicable (NA), NA, 26.11, 18.79, 14.07, and 8.32 months, respectively (p < .001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0, 1, and 2, OS was 26.11, 20.29, and 11.32 months, respectively (p < .001; AIC 2864.54, c-index 0.606). PFS periods for those IMABALI-De scores were 21.75, 12.89, 9.18, 8.0, 5.0, and 3.75 months, respectively (p < .001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores were 10.32, 7.68, and 3.57 months, respectively (p < .001; AIC 5246.61, c-index 0.574). As compared with CRAFITY score, IMABALI-De score had better AIC and c-index results for both OS and PFS.
CONCLUSION
The present results indicated that the proposed IMABALI-De score may be favorable for predicting prognosis of uHCC patients receiving Atez/Bev therapy.
Topics: Male; Humans; Aged; Carcinoma, Hepatocellular; Bevacizumab; Prognosis; Retrospective Studies; alpha-Fetoproteins; Liver Neoplasms; Antibodies, Monoclonal, Humanized
PubMed: 38577725
DOI: 10.1002/cnr2.2042 -
Taiwanese Journal of Obstetrics &... Nov 2023To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome.
OBJECTIVE
To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome.
MATERIALS AND METHODS
We retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks' gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes.
RESULTS
Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case).
CONCLUSION
A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Amniotic Fluid; alpha-Fetoproteins; Trisomy 18 Syndrome; Retrospective Studies; Chromosome Aberrations; Pregnancy Trimester, Second
PubMed: 38008506
DOI: 10.1016/j.tjog.2022.12.013 -
Journal of Medical Ultrasound 2024Prenatal diagnosis of myelomeningocele remains challenging for obstetricians, ultrasonographers, and radiologists, although the increased maternal serum... (Review)
Review
Prenatal diagnosis of myelomeningocele remains challenging for obstetricians, ultrasonographers, and radiologists, although the increased maternal serum alpha-fetoprotein level aids in the confirmative diagnosis. Fetal cervical myelomeningocele and meningocele are very rare and unique types of myelomeningocele. Prenatal diagnosis of cervical myelomeningocele and meningocele should include the differential diagnosis and association of many intracranial and spino-skeletal pathogenetic variants and genetic diseases, including subependymal nodular heterotopia and Klippel-Feil syndrome. In this report, a comprehensive review of fetal cervical myelomeningocele with its prenatal diagnosis and long-term outcomes is presented.
PubMed: 38665341
DOI: 10.4103/jmu.jmu_51_23 -
Abdominal Radiology (New York) Oct 2023To investigate the dynamic contrast-enhanced computed tomography (CECT) features and clinical characteristics of sarcomatoid hepatocellular carcinoma (S-HCC).
PURPOSE
To investigate the dynamic contrast-enhanced computed tomography (CECT) features and clinical characteristics of sarcomatoid hepatocellular carcinoma (S-HCC).
METHODS
We retrospectively reviewed the CECT data and clinical findings of 13 patients (11 male and 2 female, with an average age of 58.6 ± 11.2 years) with pathologically proven S-HCC, including 9 patients with surgical resection and 4 patients with biopsy examination. All patients underwent CECT scans. Two radiologists reviewed and evaluated general features, CECT features and extratumoral features of each lesions based on a consensus.
RESULTS
Among the thirteen tumors, a mean size of 66.7 mm was observed, ranging in diameter from 30 to 146 mm. Seven of thirteen patients had hepatitis B virus (HBV) infection and an elevation of alpha-fetoprotein (AFP) level. Most of cases located in the right lobe of liver (84.6%, 11/13). Nine of thirteen tumors showed lobulated or wavy contours and infiltrative morphology, while eight tumors presented with unclear margin. The tumor textures were mainly heterogeneous for ischemia or necrosis, with solid components dominantly in all cases. Eight of thirteen tumors exhibited "slow-in and and slow-out" dynamic enhancement pattern in CECT, with a enhancement peak in the portal venous phase. Portal vein or hepatic thrombus, adjacent organs invasion and lymph node metastasis were observed in two patients, respectively. Four of thirteen lesions occurred intrahepatic metastasis and hepatic surface retraction respectively.
CONCLUSION
S-HCC gengerally seen in elderly male with HBV infection and elevated AFP level. The CT manifestations including: large diameter, frequently hepatic right lobe involvement, lobular or wavy contours, ill-defined margins, infiltrative morphology, obvious heterogeneity and dynamic enhancement pattern of "slow-in and and slow-out" , contributed to the diagnosis of S-HCC. These tumors usually occurred hepatic surface retraction and intrahepatic metastasis.
Topics: Humans; Male; Female; Aged; Middle Aged; Carcinoma, Hepatocellular; Liver Neoplasms; alpha-Fetoproteins; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 37428205
DOI: 10.1007/s00261-023-03983-1