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Background: As cell-free nanotherapeutics, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown potential therapeutic action against liver diseases. However, their effects on autoimmune hepatitis (AIH) are not yet well understood., Methods and Results: In this study, we utilized a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model to investigate the effects of MSC-EVs on AIH. We found that MSC-EVs provide significant protection against Con A-induced hepatitis in C57BL/6 male mice, with their effectiveness being critically dependent on the gut microbiota. MSC-EVs modulate the composition of the gut microbiota, particularly by increasing the abundance of norank_f__Muribaculaceae, and impact liver metabolic profiles, leading to significant amelioration of liver injury. The identification of Acetyl-DL-Valine as a protective metabolite underscores the therapeutic potential of targeting gut‒liver axis interactions in liver diseases., Conclusion: Overall, our data demonstrate that MSC-EVs exhibit nanotherapeutic potential in Con A-induced hepatitis and provide new insights into the treatment of autoimmune hepatitis., Competing Interests: Declarations. Ethics approval and consent to participate: All experiments were performed in accordance with the institutional guidelines of the Third Affiliated Hospital of Sun Yat-sen University. The use of animals in this study was approved by the Institutional Animal Care and Use Committee of Sun Yat-sen University and was conducted in accordance with the ARRIVE guidelines 2.0. The approved study is titled “Mechanism of mesenchymal stem cells in relieving ConA-induced liver failure”, with approval granted on December 25, 2023 (Approval number: IACUC-F3-24-0102). The umbilical cords were obtained from healthy mothers at the Third Affiliated Hospital of Sun Yat-sen University with parental consent. The procedure for isolating UC-MSCs was approved by the Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. The approved study is titled “A Multicenter Randomized Controlled Clinical Study on the Treatment of Hepatitis B-Related Acute-on-Chronic Liver Failure with Allogeneic Human Umbilical Cord Mesenchymal Stem Cells”, with approval granted on December 30, 2020 (Approval number: 2020-14). Informed consent was obtained from all the subjects and/or their legal guardian(s) under the ethical committee of the Third Affiliated Hospital of Sun Yat-sen University. Consent for publication: All the authors confirm their consent for publication. Competing interests: The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper., (© 2024. The Author(s).)

This study reports a novel, eco-friendly; fast and cost-effective microwave method for synthesizing carboxymethylated graphene oxide (CMGO) from sugarcane residues. Fourier-transform infrared spectroscopy (FTIR) confirmed successful CMGO synthesis through the presence of characteristic peaks at 1567.93 and 1639.29 cm -1 (COONa vibrations) and increased CH 2 intensity compared to unmodified graphene oxide (GO). Furthermore, CMGO derived from sugarcane residues demonstrated potential in mitigating the side effects of toxic materials like carbon tetrachloride (CCl 4 ). Treatment with CMGO partially reduced elevated levels of liver enzymes (ALT and AST) and nitrogenous waste products (urea and uric acid) in CCl 4 -induced liver damage models, suggesting an improvement in liver function despite ongoing cellular damage.This work paves the way for a sustainable and economical approach to produce functionalized graphene oxide with promising biomedical applications in alleviating toxin-induced liver injury., (© 2024. The Author(s).)

Background: Reference intervals, which define an interval in which a specific proportion of measurements from a healthy population are expected to fall, are commonly used in medical practice. Synthesizing information from multiple studies through meta-analysis can provide a more precise and representative reference interval than one derived from a single study. However, the current approaches for estimating the reference interval from a meta-analysis mainly rely on aggregate data and require parametric distributional assumptions that cannot always be checked. Methods: With the availability of individual participant data (IPD), non-parametric methods can be used to estimate reference intervals without any distributional assumptions. Furthermore, patient-level covariates can be introduced to estimate personalized reference intervals that may be more applicable to specific patients. This paper introduces quantile regression as a method to estimate the reference interval from an IPD meta-analysis under the fixed effects model. Results: We compared several non-parametric bootstrap methods through simulation studies to account for within-study correlation. Under fixed effects model, we recommend keeping the studies fixed and only randomly sampling subjects with replacement within each study. Conclusion: We proposed to use the quantile regression in the IPD meta-analysis to estimate the reference interval. Based on the simulation results, we identify an optimal bootstrap strategy for estimating the uncertainty of the estimated reference interval. An example of liver stiffness measurements, a clinically important diagnostic test without explicitly established reference range in children, is provided to demonstrate the use of quantile regression in estimating both overall and subject-specific reference intervals. [ABSTRACT FROM AUTHOR]

The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians, and was introduced in response to the disproportionate number of Aboriginal and Torres Strait Islander Australians who are impacted by blood borne viruses (BBVs) and sexually transmitted infections (STIs). The goal of the program is to increase access to BBV and STI education, screening, treatment, and vaccination in recognition and response to the systemic barriers that Aboriginal and Torres Strait Islander peoples face in accessing health care. This commentary introduces a series of papers that report on various aspects of the evaluation of the Deadly Liver Mob (DLM) program. In this paper, we explain what DLM is and how we constructed an evaluation framework for this complex health promotion intervention. [ABSTRACT FROM AUTHOR]

Background: Congenital Disorders of Glycosylation (CDG) are a large group of inborn errors of metabolism with more than 140 different CDG types reported to date (1). The first characterized, PMM2-CDG, with an autosomal recessive transmission, is also the most frequent. The PMM2 gene encodes a phosphomannomutase. Here, a novel genetic variation causing PMM2-CDG is reported. Case presentation: We report the case of a French child, from healthy and unrelated parents, presenting congenital ataxia with hypotonia, hyperlaxity, inverted nipples, as well as altered coagulation parameters and liver function. Transferrin isoelectrofocusing revealed a typical type I CDG profile. Direct Sanger sequencing and quantitative PCR of PMM2 revealed a unique and novel genotype. On one allele, the patient was heterozygote with a known missense variant NM_000303.3(PMM2):c.323C > T, p.Ala108Val in exon 4. On the second allele, whole genome sequencing (WGS) indicated the presence of a novel heterozygous 70 kb deletion. Conclusion: We report in the present paper the largest known heterozygous deletion of a PMM2 gene. The observation reveals the impact of a precise diagnostic on genetic counselling: by using WGS, an erroneous conclusion of homozygosity in the case of a relatively rare variant could be avoided, and an index patient with healthy and unrelated parents correctly identified. [ABSTRACT FROM AUTHOR]

Background: Most existing algorithms have been focused on the segmentation from several public Liver CT datasets scanned regularly (no pneumoperitoneum and horizontal supine position). This study primarily segmented datasets with unconventional liver shapes and intensities deduced by contrast phases, irregular scanning conditions, different scanning objects of pigs and patients with large pathological tumors, which formed the multiple heterogeneity of datasets used in this study., Methods: The multiple heterogeneous datasets used in this paper includes: (1) One public contrast-enhanced CT dataset and one public non-contrast CT dataset; (2) A contrast-enhanced dataset that has abnormal liver shape with very long left liver lobes and large-sized liver tumors with abnormal presets deduced by microvascular invasion; (3) One artificial pneumoperitoneum dataset under the pneumoperitoneum and three scanning profiles (horizontal/left/right recumbent position); (4) Two porcine datasets of Bama type and domestic type that contains pneumoperitoneum cases but with large anatomy discrepancy with humans. The study aimed to investigate the segmentation performances of 3D U-Net in: (1) generalization ability between multiple heterogeneous datasets by cross-testing experiments; (2) the compatibility when hybrid training all datasets in different sampling and encoder layer sharing schema. We further investigated the compatibility of encoder level by setting separate level for each dataset (i.e., dataset-wise convolutions) while sharing the decoder., Results: Model trained on different datasets has different segmentation performance. The prediction accuracy between LiTS dataset and Zhujiang dataset was about 0.955 and 0.958 which shows their good generalization ability due to that they were all contrast-enhanced clinical patient datasets scanned regularly. For the datasets scanned under pneumoperitoneum, their corresponding datasets scanned without pneumoperitoneum showed good generalization ability. Dataset-wise convolution module in high-level can improve the dataset unbalance problem. The experimental results will facilitate researchers making solutions when segmenting those special datasets., Conclusions: (1) Regularly scanned datasets is well generalized to irregularly ones. (2) The hybrid training is beneficial but the dataset imbalance problem always exits due to the multi-domain homogeneity. The higher levels encoded more domain specific information than lower levels and thus were less compatible in terms of our datasets., (© 2021. The Author(s).)

Background: Advances in systems science creates an opportunity to bring a complexity perspective to health care practices and research. While medical knowledge has greatly progressed using a reductionist and mechanistic philosophy, this approach may be limited in its capacity to manage chronic and complex illness. With its holistic foundation, naturopathy is a primary health profession with a purported alignment with a complexity perspective. As such this pilot study aimed to investigate the application of complexity science principles, strategies, and tools to primary health care using naturopathy as a case study. Methods: A network mapping and analysis of the naturopathic case management process was conducted. Mind maps were created by naturopathic practitioners to reflect their clinical conceptualisation of a common paper clinical case. These mind maps were inputed into Gephi, a network mapping, exploration, and analysis software. Various layouts of the data were produced, and these were analysed using exploratory data analysis and computational network analysis. Results: Seven naturopathic practitioners participated in the study. In the combined network mapping, 133 unique elements and 399 links were identified. Obesity, the presenting issue in the case, was centrally located. Along with obesity, other keystone elements included: systemic inflammation, dysbiosis, diet, the liver, and mood. Each element was connected on average to 3.05 other elements, with a degree variation between one and 36. Six communities within the dataset were identified, comprising: the nervous system and mood, gastroinstetinal and dietary factors, systemic inflammation and obesity, the endocrine system and metabolism. Conclusions: This pilot study demonstrates that it is feasible to apply a complexity science perspective to investigating primary health care case management. This supports a shift to viewing the human organism as a complex adaptive system within primary health care settings, with implications for health care practices that are more cognisant with the treatment of chronic and complex conditions and research opportunities to capture the complex clinical reasoning processes of practitioners. [ABSTRACT FROM AUTHOR]

Background: Benign Multicystic Peritoneal Mesothelioma (BMPM) is one of the rarest diseases in medicine with only more than 200 cases worldwide. This paper aims to report a case of Benign Multicystic Peritoneal Mesothelioma that strangely arose from the liver and was long treated as Hydatid cyst. The case also had many risk factors including asbestos exposure that had not yet been linked with Benign Multicystic Peritoneal Mesothelioma. Case presentation: We report a case of a 62 years old male with a history of a perforated peptic ulcer and a cystic mass in the liver that was misdiagnosed as hydatid cyst 7 years ago. He presented with generalized abdominal pain and bloating. Image studies showed many cystic formations filled with clear fluid. An en bloc surgery was performed and a pathologic study showed a multiloculated mass lined by flat or cuboidal epithelium leading to the diagnosis of BMPM. A follow up was scheduled after 3 months revealed total recurrence. Conclusion: BMPM resembles many other cystic lesions in the abdomen and should be taken into consideration when dealing with nontypical cystic formations. Its diagnostic and treatment methods are still hazy making this disease difficult to approach. [ABSTRACT FROM AUTHOR]

Background: Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases., Methods: A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy., Results: The Boolean search found 3741 articles on Pubmed, with 3130 publications remaining when filtered by language and the presence of a full text. In total, 21 of these publications examined the key themes of the animal model described. The mortality varied from 0 to 50% depending on the surgeon's experience and the resection method. The liver resection was mainly performed with classic sutures (14 out of 21 publications) and isoflurane was used for anaesthesia (10 out of 21 publications) in combination with analgesics (buprenorphine or ketamine/xylazine). The most used mouse strain was C57BL/6 (7 of 21 publications) which was on average 11 weeks old with a weight of 23 g., Conclusion: Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method.

Liver injuries represent one of the most frequent life-threatening injuries in trauma patients. In determining the optimal management strategy, the anatomic injury, the hemodynamic status, and the associated injuries should be taken into consideration. Liver trauma approach may require non-operative or operative management with the intent to restore the homeostasis and the normal physiology. The management of liver trauma should be multidisciplinary including trauma surgeons, interventional radiologists, and emergency and ICU physicians. The aim of this paper is to present the World Society of Emergency Surgery (WSES) liver trauma management guidelines.

Background: The liver is an important organ that undertakes the metabolic function of the human body. Liver cancer has become one of the cancers with the highest mortality. In clinic, it is an important work to extract the liver region accurately before the diagnosis and treatment of liver lesions. However, manual liver segmentation is a time-consuming and boring process. Not only that, but the segmentation results usually varies from person to person due to different work experience. In order to assist in clinical automatic liver segmentation, this paper proposes a U-shaped network with multi-scale attention mechanism for liver organ segmentation in CT images, which is called MSA-UNet. Our method makes a new design of U-Net encoder, decoder, skip connection, and context transition structure. These structures greatly enhance the feature extraction ability of encoder and the efficiency of decoder to recover spatial location information. We have designed many experiments on publicly available datasets to show the effectiveness of MSA-UNet. Compared with some other advanced segmentation methods, MSA-UNet finally achieved the best segmentation effect, reaching 98.00% dice similarity coefficient (DSC) and 96.08% intersection over union (IOU). [ABSTRACT FROM AUTHOR]

The severity of liver injuries has been universally classified according to the American Association for the Surgery of Trauma (AAST) grading scale. In determining the optimal treatment strategy, however, the haemodynamic status and associated injuries should be considered. Thus the management of liver trauma is ultimately based on the anatomy of the injury and the physiology of the patient. This paper presents the World Society of Emergency Surgery (WSES) classification of liver trauma and the management Guidelines. [ABSTRACT FROM AUTHOR]

Background: Liver trauma is an important source of morbidity and mortality worldwide. A timely detection and precise evaluation of traumatic liver injury and the bleeding site is necessary. There is a need to develop better imaging modalities of hepatic injuries to increase the sensitivity of ultrasonic imaging techniques for sites of hemorrhage caused by cracks. In this study, we conduct an in silico simulation of liver crack detection and delineation using an ultrasonic shear wave imaging (USWI) based method., Methods: We simulate the generation and propagation of the shear wave in a liver tissue medium having a crack using COMSOL. Ultrasound radio frequency (RF) signal synthesis and the two-dimensional speckle tracking algorithm are applied to simulate USWI in a medium with randomly distributed scatterers. Crack detection is performed using the directional filter and the edge detection algorithm rather than the conventional inversion algorithm. Cracks with varied sizes and locations are studied with our method and the crack localization results are compared with the given crack., Results: Our pilot simulation study shows that, by using USWI combined with a directional filter cum edge detection technique, the near-end edge of the crack can be detected in all the three cracks that we studied. The detection errors are within 5%. For a crack of 1.6 mm thickness, little shear wave can pass through it and the far-end edge of the crack cannot be detected. The detected crack lengths using USWI are all slightly shorter than the actual crack length. The robustness of our method in detecting a straight crack, a curved crack and a subtle crack of 0.5 mm thickness is demonstrated., Conclusions: In this paper, we simulate the use of a USWI based method for the detection and delineation of the crack in liver. The in silico simulation helps to improve understanding and interpretation of USWI measurements in a physical scattered liver medium with a crack. This pilot study provides a basis for improved insights in future crack detection studies in a tissue phantom or liver.

Background: Ultrasound imaging is safer than other imaging modalities, because it is noninvasive and nonradiative. Speckle noise degrades the quality of ultrasound images and has negative effects on visual perception and diagnostic operations., Methods: In this paper, a nonlocal total variation (NLTV) method for ultrasonic speckle reduction is proposed. A spatiogram similarity measurement is introduced for the similarity calculation between image patches. It is based on symmetric Kullback-Leibler (KL) divergence and signal-dependent speckle model for log-compressed ultrasound images. Each patch is regarded as a spatiogram, and the spatial distribution of each bin of the spatiogram is regarded as a weighted Gamma distribution. The similarity between the corresponding bins of the two spatiograms is computed by the symmetric KL divergence. The Split-Bregman fast algorithm is then used to solve the adapted NLTV object function. Kolmogorov-Smirnov (KS) test is performed on synthetic noisy images and real ultrasound images., Results: We validate our method on synthetic noisy images and clinical ultrasound images. Three measures are adopted for the quantitative evaluation of the despeckling performance: the signal-to-noise ratio (SNR), structural similarity index (SSIM), and natural image quality evaluator (NIQE). For synthetic noisy images, when the noise level increases, the proposed algorithm achieves slightly higher SNRS than that of the other two algorithms, and the SSIMS yielded by the proposed algorithm is obviously higher than that of the other two algorithms. For liver, IVUS and 3DUS images, the NIQE values are 8.25, 6.42 and 9.01, all of which are higher than that of the other two algorithms., Conclusions: The results of the experiments over synthetic and real ultrasound images demonstrate that the proposed method outperforms current state-of-the-art despeckling methods with respect to speckle reduction and tissue texture preservation.

Background: Type 2 diabetes mellitus is a prevalent systemic disease affecting an important proportion of the population worldwide. It has been suggested that excessive reactive oxygen species generation and therefore development of an oxidative stress status is a key factor leading to diabetic complications. Accordingly, it seems that medicinal plants can offer a wide range of new antidiabetic drugs. Diplotaxis simplex (Viv.) Spreng. (Brassicaceae) is an edible plant largely distributed in the Mediterranean region. D. simplex flowers display important in vitro antioxidant potential and inhibitory activity of the α-glucosidase, a key enzyme linked to type 2 diabetes mellitus. In this paper, the antihyperglycemic potential of D. simplex flowers on diabetic rats were investigated., Methods: Bioactive substances were determined by liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HRESIMS) analysis. Animals were divided into four groups of six rats each: a normal control group, a diabetic control group, a diabetic group receiving flowers extract (200 mg/kg body mass) and a diabetic group receiving acarbose (10 mg/kg body mass) as standard drug., Results: Many glycosides of rhamnetin, isorhamnetin, quercetin and kaempferol compounds were identified in the ethanolic flowers extract. Alloxan induced hyperglycemia, manifested by a significant (p < 0.05) increase in the blood glucose level as well as in serum α-amylase activity. Furthermore, diabetic rats exhibited oxidative stress, as evidenced by a decrease in antioxidant enzymes activities and an increase in lipid peroxidation level of the pancreas, liver and kidneys. Interestingly, the oral administration of D. simplex flowers extract during 30 days restored the glycemia, α-amylase activity, serum lipid profile and antioxidant enzymes. Moreover, the flowers extract exhibited a renal protective role by decreasing the urea and creatinine levels in diabetic rats serum., Conclusions: D. simplex flowers contained bioactive compounds that possess important antioxidant and hypoglycemic properties and protected pancreas, liver and kidneys against hyperglycemia damage.

Background: Hepatic epithelioid hemangioendothelioma (EHE) is an extremely rare tumour. The aim of this study was to investigate the long-term prognosis and its relationship with treatment modalities. Methods: From March 2014 to June 2024, a total of 234 patients with histologically confirmed hepatic EHE were treated or followed up regularly by our team. The patients' clinical data at the time of diagnosis and initial treatment modalities were retrospectively collected. Kaplan–Meier curves were constructed to determine overall survival (OS). To explore prognostic factors and treatment outcomes, univariable and multivariable Cox proportional hazard models were developed. Results: A total of 228 patients were ultimately included. The median age of the cohort was 41 years. For all patients, the OS of 1-, 3- and 5-year were 96.2%, 87.9% and 84.9%, respectively. For patients who underwent liver transplantation (LT), the OS of 1- and 3-year were 62.5% and 25%, respectively. No difference was found in the OS between patients who received surgical therapy and those who did not (1-year: 100% vs. 96.9%; 3-year: 90.1% vs. 91.5%; 5-year: 87.2% vs. 88.2%; P = 0.891). In the multivariable analysis, age ≥ 60 years [HR (95% CI): 4.207 (1.266–13.973), P = 0.019], the size of the largest lesion > 10 cm [HR (95% CI): 12.140 (1.419–103.872), P = 0.023] and LT [HR (95% CI): 5.502 (1.343–22.536), P = 0.018] were poor prognostic factors. Conclusions: Compared with nonsurgical therapy, surgical therapy has no advantage in terms of long-term survival. The role of LT in the management of hepatic EHE should be reevaluated. Age ≥ 60 years and the size of the largest lesion > 10 cm are poor prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Hypoxia stress resulted in mortality during the fish aquaculture program, affecting the sustainable development of the aquaculture industry. The Egyptian strain of O. niloticus showed a strong ability to hypoxia. In this study, a Nile tilapia strain that was kept and selected for 45 years by the author's team was used to elucidate the mechanism of the hypoxia response in the liver, including the identification of metabolic pathways and genes, involved in the hypoxia response of this strain. Results: The effects of hypoxia stress were detected at 0-hour, 6-hour, and 72-hour time points (0 h, 6 h, 72 h) on tilapia liver at 1 mg/L dissolved oxygen conditions. The blood triglyceride, blood glucose and cholesterol values exhibited significantly different change trends, but the hemoglobin content showed no significant differences between 0 h, 6 h and 72 h (P > 0.05). The activities of catalase (CAT), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), lactate dehydrogenase (LDH), and acid phosphatase (ACP) in the liver tissue gradually increased at 0 h, 6 h and 72 h (P < 0.05). Histological analyses revealed structural changes in intracellular lipid droplets, nuclear migration and dissolution, and cell vacuolization in liver tissues. Six pathways were identified as the main enriched metabolic pathways according to the transcriptome profiling analysis, which were protein processing in endoplasmic reticulum, steroid biosynthesis, peroxisome, PPAR signaling pathway, glycolysis/gluconeogenesis and Insulin signaling pathway. The expressions of the important differentially expressed genes were verified by qPCR analysis, including erola, LOC100692144, sqle, cratb, pipox, cpt1a2b, hik and acss2l, ehhadh, prkcz, fasn and plaa, which showed the same expressions trends as those of RNA-Seq. Conclusions: The Nile tilapia strain improves the abilities of hypoxia response through energy metabolism. Antioxidant enzyme measurements in the liver indicate that these five antioxidant enzymes play important roles in protecting the body from hypoxic damage. The histological changes in liver cells indicate that the damage caused by hypoxia stress. The immune-related metabolic pathways and energy metabolism-related pathways were obtained by transcriptome profiling, and these metabolic pathways and the differentially expressed genes selected from these metabolic pathways may be involved in the mechanism of hypoxia tolerance in this strain. These findings provide a better understanding of the hypoxia response mechanism of fish, and represent a useful resource for the genetic breeding of O. niloticus. [ABSTRACT FROM AUTHOR]

Background: Human T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term. Methods: This data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated. Results: Multivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039). Conclusion: Individuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus's involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue. [ABSTRACT FROM AUTHOR]

Background: Situs inversus totalis is a rare congenital anomaly characterized by a mirror-image orientation of abdominal, and in some cases, thoracic organs. Here, we report our situs inversus totalis transplantation experience and further review liver transplantations in adult recipients and donors with situs inversus totalis. Case presentation: We describe three cases with situs inversus totalis. The first case was liver transplantation in a recipient (a 61-year-old Iranian man) with situs inversus totalis, the second was a liver transplantation from a donor (a 52-year-old Iranian woman) with situs inversus totalis, and finally, for the first time, a simultaneous pancreas and kidney transplantation in a recipient (a 26-year-old Iranian man) with situs inversus totalis. In patient one, hepatectomy could be performed according to the standard method and on the basis of preoperative studies. Hepatic vein and arterial anastomosis were performed as in every other patient without situs inversus totalis. To prevent biliary complications, a Roux-en-Y hepaticojejunostomy was performed. In patient two, implantation time, suprahepatic vein, portal vein, arterial, and biliary reconstruction could be done as in any other case without situs inversus totalis. Plication of the right-sided diaphragm and fixation of the falciform ligament was done for our patient. In patient three, systemic drainage was preferred to portal flow for establishing the outflow drainage of the pancreas compared with otherwise normal patients. Conclusion: Although situs inversus totalis is a rare condition, our reported techniques are suitable, considering advantages such as easier accessibility, more acceptable placement of the implanted organs regarding vascular variations, and the appropriate location of the allograft in the proximity of other organs. [ABSTRACT FROM AUTHOR]

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant that disrupts hepatic function leading to steatotic liver disease (SLD)-like pathologies, such as steatosis, steatohepatitis, and fibrosis. These effects are mediated by the aryl hydrocarbon receptor following changes in gene expression. Although diverse cell types are involved, initial cell-specific changes in gene expression have not been reported. In this study, differential gene expression in hepatic cell types was examined in male C57BL/6 mice gavaged with 30 µg/kg of TCDD using single-nuclei RNA-sequencing. Ten liver cell types were identified with the proportions of most cell types remaining unchanged, except for neutrophils which increased at 72 h. Gene expression suggests TCDD induced genes related to oxidative stress in hepatocytes as early as 2 h. Lipid homeostasis was disrupted in hepatocytes, macrophages, B cells, and T cells, characterized by the induction of genes associated with lipid transport, steroid hormone biosynthesis, and the suppression of β-oxidation, while linoleic acid metabolism was altered in hepatic stellate cells (HSCs), B cells, portal fibroblasts, and plasmacytoid dendritic cells. Pro-fibrogenic processes were also enriched, including the induction retinol metabolism genes in HSCs and the early induction of anti-fibrolysis genes in hepatocytes, endothelial cells, HSCs, and macrophages. Hepatocytes also had gene expression changes consistent with hepatocellular carcinoma. Collectively, these findings underscore the effects of TCDD in initiating SLD-like phenotypes and identified cell-specific gene expression changes related to oxidative stress, steatosis, fibrosis, cell proliferation and the development of HCC. [ABSTRACT FROM AUTHOR]

Background: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer commonly used in a wide variety of products, including medical devices. It is rapidly metabolized in the liver into various metabolites upon absorption through oral ingestion, dermal absorption, and inhalation. DEHP is classified as a non-genotoxic hepatocarcinogen in rodents, as its chronic exposure has been associated with the development of liver cancer in these animals, but most genotoxicity studies have been negative. Epidemiologic studies in humans suggest that long-term high intakes of DEHP may be a risk factor for liver dysfunction. The repeated-dose liver micronucleus (RDLMN) assay is a well-established method for assessing chromosomal changes caused by hepatic genotoxins and/or carcinogens. It is particularly valuable for detecting substances that undergo metabolic activation, especially when the metabolite has a short half-life or does not reach the bone marrow effectively. Therefore, we investigated whether the RDLMN assay could detect DEHP-induced micronucleus formation in the liver following a 14 or 28-day treatment. Results: We report that the RDLMN assay demonstrated an increased frequency of hepatic micronuclei in rats exposed to DEHP for 14 or 28 days. The increases in micronuclei correlated with hepatomegaly, an established response to phthalates in the liver. Conversely, no such increases were observed in the micronucleus assay using bone marrow from these rats. Conclusion: The detection of DEHP-induced micronuclei by the RDLMN assay suggests that this assay could detect the potential genotoxicity and hepatocarcinogenicity of DEHP. It also demonstrated the utility of the RDLMN assay in identifying metabolically activated hepatic carcinogens. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study is to show how sodium nitrite alters the histology of submandibular salivary glands and livers of Albino rats, as well as how chlorogenic acid may have therapeutic benefits. Methods: A sample size of thirty male Sprague Dawley Albino rats weighing between 100 and 150 g (5-6 weeks old) was randomly allocated into 3 equal groups. Group I: rats were used as controls and were given phosphate buffer solution, whereas Group II: rats were given an 80 mg/kg sodium nitrites (SN) daily dissolved in distilled water. The rats in Group III were given a daily dose of 80 mg/kg SN dissolved in distilled water and after 6 hours each rat received 50 mg/mL freshly prepared chlorogenic acid (CGA) every other day. For 12 weeks, all treatment modalities will be administered orally, every day. After the experiment, all rats were euthanized. Samples from salivary glands and livers were processed and stained with H&E and interleukin 6 (IL 6). Malondialdehyde (MDA) and superoxide dismutase (SOD) enzymes were detected using an ELISA assay. Results: Groups III had nearly comparable findings to Group I regarding histological pattern with normal submandibular glands and livers features. Group III salivary gland treated with CGA exhibited higher SOD levels (20.60±4.81 U/g) in comparison to the SN group, and lower MDA levels (111.58±28.28 nmol/mg) in comparison to the SN treated samples. In comparison to the SN group, CGA treatment significantly reduced MDA levels in liver samples (167.56±21.17 nmol/mg) and raised SOD (30.85±6.77 U/g). Conclusions: Chlorogenic acid has a protective effect against salivary gland and liver toxicity induced by SN in rats. This was mediated via the anti-inflammatory and antioxidative properties of CGA and the restoration of oxidant/antioxidant balance in rat salivary gland and liver. [ABSTRACT FROM AUTHOR]

Background: Bupleuri Radix (in Chinese Chaihu), the dried roots of Bupleurum Chinense DC, is a traditional Chinese medicine widely used to treat fever, hepatitis, jaundice, nephritis, dizziness. When baked with vinegar, its effect is more focused on liver related disease. This paper was undertaken to determine the best vinegar amount in the processing and explore its key efficacy components., Methods: Hepatoprotective effects of Radix Bupleuri after processing with different amount of vinegar (1:5, 2:5, 3:5) were investigated on liver hurt rats, and the change of constituents were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)., Results: With the increasing amount of vinegar, the hepatoprotective effects of vinegar-baked Radix Bupleuri (VBRB) and the content of saikosaponin b2 increased., Conclusion: These results suggested that vinegar amount in the process affected the pharmacological effect of VBRB significantly and saikosaponin b2 may be the key efficacy component of it.

Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1β and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential., Competing Interests: The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.

Mesenchymal stem cells (MSCs) represent an attractive cell type for research and therapy due to their ability to proliferate, differentiate, modulate immune reactions, and secrete trophic factors. MSCs exist in a multitude of tissues, including bone marrow, umbilical cord, and adipose tissues. Moreover, MSCs have recently been isolated from the liver. Compared with other MSC types, liver-derived human MSCs (LHMSCs) possess general morphologies, immune functions, and differentiation capacities. Interestingly, LHMCSs produce higher levels of pro-angiogenic, anti-inflammatory, and anti-apoptotic cytokines than those of bone marrow-derived MSCs. Thus, these cells may be a promising therapeutic source for liver diseases. This paper summarizes the biological characteristics of LHMSCs and their potential benefits and risks for the treatment of liver diseases.

Background: One of the major issues in current pharmaceutical development is potential hepatotoxicity and drug-induced liver damage. This is due to the unique metabolic processes performed in the liver to prevent accumulation of a wide range of chemicals in the blood. Recently, we developed a physiologically-based lattice model to address the transport and metabolism of drugs in the liver lobule (liver functional unit)., Method: In this paper, we extend our idealized model to consider structural and spatial variability in two and three dimensions. We introduce a hexagonal-based model with one input (portal vein) and six outputs (hepatic veins) to represent a typical liver lobule. To capture even more realistic structures, we implement a novel sequential diffusion-limited aggregation (DLA) method to construct a morphological sinusoid network in the lobule. A 3D model constructed with stacks of multiple 2D sinusoid realizations is explored to study the effects of 3D structural variations. The role of liver zonation on drug metabolism in the lobule is also addressed, based on flow-based predicted steady-state O2 profiles used as a zonation indicator., Results: With this model, we analyze predicted drug concentration levels observed exiting the lobule with their detailed distribution inside the lobule, and compare with our earlier idealized models. In 2D, due to randomness of the sinusoidal structure, individual hepatic veins respond differently (i.e. at different times) to injected drug. In 3D, however, the variation of response to the injected drug is observed to be less extreme. Also, the production curves show more diffusive behavior in 3D than in 2D., Conclusion: Although, the individual producing ports respond differently, the average lobule production summed over all hepatic veins is more diffuse. Thus the net effect of all these variations makes the overall response smoother. We also show that, in 3D, the effect of zonation on drug production characteristics appears quite small. Our new biophysical structural analysis of a physiologically-based 3D lobule can therefore form the basis for a quantitative assessment of liver function and performance both in health and disease.