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Indian Journal of Pediatrics Mar 2024
Topics: Humans; Respiratory Insufficiency; Muscular Dystrophies; Muscular Diseases; Scoliosis; Mallory Bodies
PubMed: 37740884
DOI: 10.1007/s12098-023-04847-8 -
Clinical Gastroenterology and... Feb 2024Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH...
BACKGROUND & AIMS
Antimüllerian hormone (AMH) is a marker of ovarian reserve with emerging data linking lower levels to some metabolic and inflammatory diseases in women. Whether AMH levels influence nonalcoholic fatty liver disease (NAFLD) is unknown.
METHODS
Leveraging the NASH Clinical Research Network we determined the association of AMH levels within 6 months of liver biopsy with presence and severity of histologic measures of NAFLD in premenopausal women. Outcomes included presence of nonalcoholic steatohepatitis (NASH), presence and severity of fibrosis, and NAFLD Activity Score and its components. Logistic and ordinal logistic regression models were adjusted for age, race/ethnicity, homeostatic model assessment for insulin resistance, body mass index, dyslipidemia, polycystic ovary syndrome, estrogen-progestin use, and menstrual cyclicity.
RESULTS
Median cohort age was 35 years; 73% were white and 24% Hispanic. Thirty-three percent had diabetes, 81% had obesity, and 95% had dyslipidemia. On biopsy 71% had NASH, 68% had any fibrosis, and 15% had advanced fibrosis. On adjusted analysis (n = 205), higher AMH quartiles were inversely associated with NAFLD histology including prevalent NASH (adjusted odds ratio [AOR], 0.64; 95% confidence interval [CI], 0.41-1.00), NAFLD Activity Score ≥5 (AOR, 0.52; 95% CI, 0.35-0.77), Mallory hyaline (AOR, 0.54; 95% CI, 0.35-0.82), and higher fibrosis stage (AOR, 0.70; 95% CI, 0.51-0.98). The protective effects of AMH were more pronounced among women without polycystic ovary syndrome (n = 164), including lower odds of NASH (AOR, 0.53; 95% CI, 0.32-0.90) and any NASH fibrosis (AOR, 0.54; 95% CI, 0.32-0.93).
CONCLUSIONS
AMH may reflect a unique biomarker of NASH in premenopausal women and findings suggest a novel link between reproductive aging and histologic severity of NAFLD in women.
Topics: Humans; Female; Adult; Non-alcoholic Fatty Liver Disease; Anti-Mullerian Hormone; Polycystic Ovary Syndrome; Ovarian Reserve; Liver Cirrhosis; Dyslipidemias; Liver; Biopsy
PubMed: 37678489
DOI: 10.1016/j.cgh.2023.08.020 -
International Journal of Gynecological... May 2024Mallory-Denk bodies (MBD), described in alcoholic hepatitis, are composed of intermediate filaments admixed with other proteins. These cytoplasmic inclusions are...
Mallory-Denk bodies (MBD), described in alcoholic hepatitis, are composed of intermediate filaments admixed with other proteins. These cytoplasmic inclusions are irregularly shaped and eosinophilic as seen under the light microscope. MBD-like inclusions have rarely been described outside the hepatobiliary tree. Though rare, intracytoplasmic inclusions have been reported in ovarian fibromas. This study evaluates a series of torsed ovarian fibromas with intracytoplasmic inclusions resembling MDBs. Forty-three ovarian fibromas were retrieved from the pathology archives. The H&E slides were evaluated for the presence of MBD-like inclusions and histologic evidence of torsion. The cases with histologic features of torsion were included in the study group while the nontorsed fibromas formed the control group. Among the 15 cases of fibromas with torsion, MBD-like intracytoplasmic inclusions were seen in 5 cases, predominantly in the interface between necrotic areas and viable stroma. None of the cases from the control group showed any inclusions. There was no significant difference in the size of the fibroma or patient demographics between cases with and without inclusions. The inclusions were positive for cytokeratin and ubiquitin while being negative for per acidic Schiff and periodic acid-Schiff with diastase reaction, in the 3 cases selected for immunohistochemistry and special stains. Electron microscopy of the index case revealed a predominance of type 3 Mallory hyaline. This is the first report describing MDB-like inclusions in ovarian fibromas. These MDB-like inclusions appear to be limited to a fraction of ovarian fibromas that underwent torsion, suggesting that these inclusions likely result from subacute hypoxic damage to the cells.
Topics: Humans; Hepatocytes; Inclusion Bodies; Ubiquitin; Keratins; Fibroma
PubMed: 37562060
DOI: 10.1097/PGP.0000000000000974 -
PeerJ. Computer Science 2023Figures and captions in medical documentation contain important information. As a result, researchers are becoming more interested in obtaining published medical figures...
BACKGROUND
Figures and captions in medical documentation contain important information. As a result, researchers are becoming more interested in obtaining published medical figures from medical papers and utilizing the captions as a knowledge source.
METHODS
This work introduces a unique and successful six-fold methodology for extracting figure-caption pairs. The A-torus wavelet transform is used to retrieve the first edge from the scanned page. Then, using the maximally stable extremal regions connected component feature, text and graphical contents are isolated from the edge document, and multi-layer perceptron is used to successfully detect and retrieve figures and captions from medical records. The figure-caption pair is then extracted using the bounding box approach. The files that contain the figures and captions are saved separately and supplied to the end useras theoutput of any investigation. The proposed approach is evaluated using a self-created database based on the pages collected from five open access books: Sergey Makarov, Gregory Noetscher and Aapo Nummenmaa's book "Brain and Human Body Modelling 2021", "Healthcare and Disease Burden in Africa" by Ilha Niohuru, "All-Optical Methods to Study Neuronal Function" by Eirini Papagiakoumou, "RNA, the Epicenter of Genetic Information" by John Mattick and Paulo Amaral and "Illustrated Manual of Pediatric Dermatology" by Susan Bayliss Mallory, Alanna Bree and Peggy Chern.
RESULTS
Experiments and findings comparing the new method to earlier systems reveal a significant increase in efficiency, demonstrating the suggested technique's robustness and efficiency.
PubMed: 37547417
DOI: 10.7717/peerj-cs.1452 -
Cancer Science Oct 2023Patients with nonalcoholic fatty liver disease (NAFLD) continue to increase with the epidemics of obesity, and NAFLD is estimated to become the most prevalent etiology... (Review)
Review
Patients with nonalcoholic fatty liver disease (NAFLD) continue to increase with the epidemics of obesity, and NAFLD is estimated to become the most prevalent etiology of hepatocellular carcinoma (HCC). Recently, NAFLD-HCC has been recognized to have clinico-histologically and molecularly distinct features from those from other etiologies, including a lower incidence rate of HCC and less therapeutic efficacy to immune checkpoint inhibitors (ICIs). Consistent with the clinical observations that up to 50% of NAFLD-HCC occurs in the absence of cirrhosis, the imbalance of pro- and antitumorigenic hepatic stellate cells termed as myHSC and cyHSC can contribute to the creation of an HCC-prone hepatic environment, independent of the absolute fibrosis abundance. Immune deregulations by accumulated metabolites in NAFLD-affected livers, such as a fatty-acid-induced loss of cytotoxic CD4 T cells serving for immune surveillance and "auto-aggressive" CXCR6+ CD8 T cells, may promote hepatocarcinogenesis and diminish therapeutic response to ICIs. Steatohepatitic HCC (SH-HCC), characterized by the presence of fat accumulation in tumor cells, ballooned tumor cells, Mallory-Denk body, interstitial fibrosis, and intratumor immune cell infiltration, may represent a metabolic reprogramming for adapting to a lipid-rich tumor microenvironment by downregulating CPT2 and leveraging its intermediates as an "oncometabolite." Genome-wide analyses suggested that SH-HCC may be more responsive to ICIs given its mutual exclusiveness with β-catenin mutation/activation that promotes immune evasion. Thus, further understanding of NAFLD-specific hepatocarcinogenesis and HCC would enable us to improve the current daily practice and eventually the prognoses of patients with NAFLD.
PubMed: 37545384
DOI: 10.1111/cas.15925 -
Laboratory Investigation; a Journal of... Oct 2023Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity...
Nonalcoholic fatty liver disease is rapidly becoming one of the most common causes of chronic liver disease worldwide and is the leading cause of liver-related morbidity and mortality. A quantitative assessment of the degree of steatosis would be more advantageous for diagnostic evaluation and exploring the patterns of disease progression. Here, multiphoton microscopy, based on the second harmonic generation and 2-photon excited fluorescence, was used to label-free image the samples of nonalcoholic fatty liver. Imaging results confirm that multiphoton microscopy is capable of directly visualizing important pathologic features such as normal hepatocytes, hepatic steatosis, Mallory bodies, necrosis, inflammation, collagen deposition, microvessel, and so on and is a reliable auxiliary tool for the diagnosis of nonalcoholic fatty liver disease. Furthermore, we developed an image segmentation algorithm to simultaneously assess hepatic steatosis and fibrotic changes, and quantitative results reveal that there is a correlation between the degree of steatosis and collagen content. We also developed a feature extraction program to precisely display the spatial distribution of hepatocyte steatosis in tissues. These studies may be beneficial for a better clinical understanding of the process of steatosis as well as for exploring possible therapeutic targets.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver; Diagnostic Imaging; Image Processing, Computer-Assisted; Collagen; Microscopy, Fluorescence, Multiphoton
PubMed: 37517702
DOI: 10.1016/j.labinv.2023.100223 -
Phytomedicine : International Journal... Sep 2023To study the effect of ShenKang Injection (SKI) on the kidneys of DKD rats and its effect on oxidative stress mediated by the Keap1/Nrf2/Ho-1 signaling pathway through...
OBJECTIVE
To study the effect of ShenKang Injection (SKI) on the kidneys of DKD rats and its effect on oxidative stress mediated by the Keap1/Nrf2/Ho-1 signaling pathway through network pharmacology and in vivo and in vitro experiments.
METHODS
SKI drug targets were screened by TCMSP, DKD targets were screened by GenGards, OMIM, Drugbank, TTD, and Disgenet databases, and the two intersected for PPI network analysis and target prediction was performed by GO and KEGG. A total of 40 SD rats were randomly divided into 10 in the control group and 30 in the model group. After the model group was fed 8 W with high-sugar and high-fat diets, a DKD model was constructed by one-time intraperitoneal injection of streptozotocin (35 mg/kg). According to the weight, the model animals were randomly divided into three groups: 8 for model validation group, 8 for Irbesartan (25 mg/kg daily) group, and 8 for SKI group (5 ml/kg). Gavaged deionized water was given to the control group and the model validation group equally. The general conditions of the rats were observed, their body weights measured and their urine volumes recorded for 24 h. After the intervention of 16 W, serum was collected to detect Urea, Scr, blood lipids, and oxidative stress and lipid peroxidation indicators; Transmission electron microscopy, HE and Mallory staining were used to observe the pathological morphology of renal tissue. Immunohistochemistry and RT-PCR were used to detect the expression of Keap1, Nrf2, Ho-1, Gpx4 proteins and mRNA in rat kidney tissues. HK-2 cells were cultured in vitro and divided into: the control group, AGEs (200 μg/ml) group and AGEs + SKI group. The cell activity of the groups was detected using CCK-8 after 48 h of cell culture, and ROS were detected using fluorescent probes. Gpx4 expression was detected by immunofluorescence, while Keap1, Nrf2, Ho-1, and Gpx4 were detected by Western Blot.
RESULTS
Network pharmacological analysis predicted that SKI may delay DKD kidney injury by affecting redox-related signaling pathways and mitigating AGEs-induced oxidative stress. In the animal experiment, compared with the model validation group, the general state of rats in the SKI group was improved, and 24-hour urine protein levels were significantly reduced, and the Scr in the serum was reduced. A decreasing trend was seen in Urea, and TC, TG, and LDL levels significantly decreased and the levels of ROS, LPO and MDA were significantly lowered. Pathological staining showed that renal interstitial fibrosis was significantly improved, and electron microscopy showed that foot process effacement was alleviated. Immunohistochemistry and RT-PCR showed decreased expression of Keap1 protein and mRNA in kidney tissues of the SKI group. Additionally, Nrf2, Ho-1, and Gpx4 proteins and mRNA were expressed significantly. In the cell experiment, after 48 h treatment with AGEs, ROS in HK-2 cells increased significantly and cell activity decreased significantly, while cell activity in AGEs + SKI group increased significantly and ROS decreased. The expression of Keap1 protein in HK-2 cells in the AGEs + SKI group decreased, while the expression of Nrf2, Ho-1 and Gpx4 proteins increased significantly.
CONCLUSION
SKI can protect kidney function in DKD rats, delay DKD progression, inhibit AGEs-induced oxidative stress damage in HK-2 cells, and the mechanism of SKI to improve DKD may be achieved by activating the Keap1/Nrf2/Ho-1 signal transduction pathway.
Topics: Rats; Animals; Reactive Oxygen Species; Diabetic Nephropathies; Rats, Sprague-Dawley; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Network Pharmacology; Oxidative Stress; Signal Transduction; Urea; Glycation End Products, Advanced; Diabetes Mellitus
PubMed: 37392674
DOI: 10.1016/j.phymed.2023.154915 -
World Journal of Gastrointestinal... May 2023Mallory-Weiss syndrome (MWS), representing a linear mucosal laceration at the gastroesophageal junction, is a quite frequent cause of upper gastrointestinal bleeding,...
BACKGROUND
Mallory-Weiss syndrome (MWS), representing a linear mucosal laceration at the gastroesophageal junction, is a quite frequent cause of upper gastrointestinal bleeding, usually induced by habitual vomiting. The subsequent cardiac ulceration in this condition is likely due to the concomitance of increased intragastric pressure and inappropriate closure of the gastroesophageal sphincter, collectively inducing ischemic mucosal damage. Usually, MWS is associated with all vomiting conditions, but it has also been described as a complication of prolonged endoscopic procedures or ingested foreign bodies.
CASE SUMMARY
We described herein a case of upper gastrointestinal bleeding in a 16-year-old girl with MWS and chronic psychiatric distress, the latter of which deteriorated following her parents' divorce. The patient, who was residing on a small island during the coronavirus disease 2019 pandemic lockdown period, presented with a 2-mo history of habitual vomiting, hematemesis, and a slight depressive mood. Ultimately, a huge intragastric obstructive trichobezoar was detected and discovered to be due to a hidden habit of continuously eating her own hair; this habit had persisted for the past 5 years until a drastic reduction in food intake and corresponding weight loss occurred. The relative isolation in her living status without school attendance had worsened her compulsory habit. The hair agglomeration had reached such enormous dimensions and its firmness was so hard that its potential for endoscopic treatment was judged to be impossible. The patient underwent surgical intervention instead, which culminated in complete removal of the mass.
CONCLUSION
According to our knowledge, this is the first-ever described case of MWS due to an excessively large trichobezoar.
PubMed: 37342849
DOI: 10.4240/wjgs.v15.i5.972 -
Histopathology Oct 2023According to the last WHO classification, steatohepatitic hepatocellular carcinoma (SH-HCC) is recognized as a distinct HCC subtype, even though a consensual definition...
AIMS
According to the last WHO classification, steatohepatitic hepatocellular carcinoma (SH-HCC) is recognized as a distinct HCC subtype, even though a consensual definition is still lacking. The objectives of the study were to carefully describe the morphological features of SH-HCC and evaluate its impact on prognosis.
METHODS AND RESULTS
We conducted a single-centre retrospective study including 297 surgically resected HCC. Pathological features including SH criteria (steatosis, ballooning, Mallory-Denk bodies, fibrosis, and inflammation) were assessed. SH-HCC was defined by the presence of at least four of the five SH criteria and the SH component represented >50% of the tumour area. According to this definition, 39 (13%) HCC cases corresponded to SH-HCC and 30 cases (10%) corresponded to HCC with an SH component (<50%). SH criteria in SH-HCC and non-SH-HCC were distributed as follows: ballooning (100% versus 11%), fibrosis (100% versus 81%), inflammation (100% versus 67%), steatosis (92% versus 8%), and Mallory-Denk bodies (74% versus 3%). Inflammation markers (c-reactive protein [CRP] and serum amyloid A [SAA]) were significantly more expressed in SH-HCC compared to non-SH-HCC (82% versus 14%, P = <0.001). Five-year recurrence-free survival (RFS) and 5-year overall survival (OS) were similar for SH-HCC and non-SH-HCC (P = 0.413 and P = 0.866, respectively). The percentage of SH component does not impact OS and RFS.
CONCLUSION
We confirm in a large cohort the relatively high prevalence (13%) of SH-HCC. Ballooning is the most specific criteria for this subtype. The percentage of the SH component does not impact prognosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Retrospective Studies; Fatty Liver; Prognosis; Fibrosis; Inflammation
PubMed: 37222200
DOI: 10.1111/his.14941 -
Developmental Cell Jul 2023In addition to membranous organelles, autophagy selectively degrades biomolecular condensates, in particular p62/SQSTM1 bodies, to prevent diseases including cancer....
In addition to membranous organelles, autophagy selectively degrades biomolecular condensates, in particular p62/SQSTM1 bodies, to prevent diseases including cancer. Evidence is growing regarding the mechanisms by which autophagy degrades p62 bodies, but little is known about their constituents. Here, we established a fluorescence-activated-particle-sorting-based purification method for p62 bodies using human cell lines and determined their constituents by mass spectrometry. Combined with mass spectrometry of selective-autophagy-defective mouse tissues, we identified vault, a large supramolecular complex, as a cargo within p62 bodies. Mechanistically, major vault protein directly interacts with NBR1, a p62-interacting protein, to recruit vault into p62 bodies for efficient degradation. This process, named vault-phagy, regulates homeostatic vault levels in vivo, and its impairment may be associated with non-alcoholic-steatohepatitis-derived hepatocellular carcinoma. Our study provides an approach to identifying phase-separation-mediated selective autophagy cargoes, expanding our understanding of the role of phase separation in proteostasis.
Topics: Animals; Humans; Mice; Sequestosome-1 Protein; Proteomics; Autophagy; Liver Neoplasms; Organelles
PubMed: 37192622
DOI: 10.1016/j.devcel.2023.04.015