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Ethnopharmacological Relevance: Chrysanthemum indicum L., Chrysanthemum morifolium Ramat., Buddleja officinalis Maxim., and Sophora japonica L. have the effects of "Clearing the liver" and "Improving vision". Flavonoids are their main active ingredients, but there are few reports on their simultaneous liver and eye protective effects., Aim of the Study: Overview of the role of flavonoids of the four medicinal flowers (FFMF) in the prevention and treatment of liver and eye diseases., Materials and Methods: The Web of Science, PubMed, CNKI, Google Scholar, and WanFang databases were searched for FFMF. Using "hepatitis", "liver fibrosis", "liver cancer", "dry eye syndrome", "cataracts", "glaucoma", "age-related macular degeneration", and "diabetic retinopathy" as the keywords, we summarized the main pathological mechanisms of these diseases and the role of FFMF in their prevention and treatment., Results: We found that the four medicinal flowers contained a total of 125 flavonoids. They can maintain liver and eye homeostasis by regulating pathological mechanisms such as oxidative stress, inflammation, endoplasmic reticulum stress, mitochondrial dysfunction, glucose and lipid metabolism disorders, and programmed cell death, exerting the effect of "clearing the liver and improving vision"., Conclusion: FFMF have a series of beneficial properties such as antioxidant, anti-inflammatory, antiviral, and antifibrotic activity, and the regulation of angiogenesis, glycolipid metabolism and programmed cell death, which may explain the efficacy of the four traditional Chinese medicines for "Clearing the liver" and "Improving vision"., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Phyllanthus genus is very important plant traded as a raw herbal medicine in India. Commonly known as 'Bhumyamalaki' (Phyllanthus species) has been used for the prevention and treatment of jaundice. Phyllanthus is rich in diversity of bioactive compounds such as lignans, alkaloids, terpenoids, flavonoids, and tannins. Among some metabolites such as phyllanthin, hypophyllanthin, 8, 9-epoxy brevifolin, brevifolin, quercetin, gallic acid, elagic acid, and brevifolin carboxylate have been shown to have hepatoprotective and antioxidant activity found in this genus. The basic objective of this review was to overview the hepatoprotective activity based on the other available data from various plants of the Phyllanthus species including Phyllanthus amarus, Phyllanhtus urinaria, Phyllanthus fraternus, Phyllanthus maderaspatenis, Phyllanthus simplex, Phyllanthus emblica, Phyllanthus debillis, Phyllanthus tenellus, Phyllanthus polyphyllus, Phyllanthus reticulates, Phyllanthus indofischerii, Phyllanthus acidus, Phyllanthus niruri, Phyllanthus rheedii, Phyllanthus kozhikodianus, and Phyllanthus longiflorus. These species studied had considerable hepatoprotective potential. The secondary data, each in vitro and in vivo studies confirm the capacity of Phyllanthus species used as a remedy for jaundice or liver disease in addition to having antioxidants. Furthermore, it could be concluded that herbal drugs have the least side effects and are taken into considered safe for human health, they are able to substantially alternative synthetic drugs in the future., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Several ongoing trials are evaluating incretin-based therapies, including GLP-1 receptor agonists, for their effects on CKD and MASLD. These studies will offer insights into their potential for metabolic diseases in people with type 2 diabetes and obesity., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Thyroid hormone action is involved in virtually all physiological processes. It is well known that the liver and thyroid are intimately linked, with thyroid hormone playing important roles in de novo lipogenesis, beta-oxidation (fatty acid oxidation), cholesterol metabolism, and carbohydrate metabolism. Clinical and mechanistic research studies have shown that thyroid hormone can be involved in chronic liver diseases, including alcohol-associated or NAFLD and HCC. Thyroid hormone action and synthetic thyroid hormone analogs can exert beneficial actions in terms of lowering lipids, preventing chronic liver disease and as liver anticancer agents. More recently, preclinical and clinical studies have indicated that some analogs of thyroid hormone could also play a role in the treatment of liver disease. These synthetic molecules, thyromimetics, can modulate lipid metabolism, particularly in NAFLD/NASH. In this review, we first summarize the thyroid hormone signaling axis in the context of liver biology, then we describe the changes in thyroid hormone signaling in liver disease and how liver diseases affect the thyroid hormone homeostasis, and finally we discuss the use of thyroid hormone-analog for the treatment of liver disease., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Injectable hydrogels are a sub-type of hydrogels which can be delivered into the host in a minimally invasive manner. They can act as carriers to encapsulate and deliver cells, drugs or active biomolecules across several disease conditions. Polymers, either synthetic or natural, or even a combination of the two, can be used to create injectable hydrogels. Clinically approved injectable hydrogels are being used as dressings for burn wounds, bone and cartilage reconstruction. Injectable hydrogels have recently gained tremendous attention for their delivery into the liver in pre-clinical models. However, their efficacy in clinical studies remains yet to be established. In this article, we describe principles for the design of these injectable hydrogels, delivery strategies and their potential applications in facilitating liver regeneration and ameliorating injury. We also discuss the several constraints related to translation of these hydrogels into clinical settings for liver diseases and deliberate some potential solutions to combat these challenges., (© 2024 Wiley-VCH GmbH.)

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic hepatobiliary diseases, such as inflammation, hepatic stellate cell activation and proliferation, and extracellular matrix production, are being developed. Etiology-specific treatments, such as those for hepatitis B and C viruses, are already in clinical use, and efforts to develop new, targeted therapies for other chronic hepatobiliary diseases are ongoing. In this review, we highlight the major molecular changes occurring in patients affected by metabolic dysfunction-associated steatotic liver disease, viral hepatitis (Delta virus), and autoimmune chronic liver diseases (autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis). Further, we describe how this knowledge is linked to current molecular therapies as well as ongoing preclinical and clinical research on novel targeting strategies, including nucleic acid-, mesenchymal stromal/stem cell-, and extracellular vesicle-based options. Much clinical development is obviously still missing, but the plethora of promising potential treatment strategies in chronic hepatobiliary diseases holds promise for a future reversal of the current increase in morbidity and mortality in this group of patients.

A 9-year-old neutered male cairn terrier dog was initially presented because of inappetence, increased respiratory effort, and occasional coughing. A cavitary lung mass was diagnosed using CT and removed with lung lobectomy. Histopathology of the mass revealed necrosuppurative inflammation with acid-fast rod bacteria in macrophages, with Mycobacterium spp. a possible cause. Routine bacterial culture of a lung-lesion swab was negative for growth. The dog improved and did not show any clinical signs for 9 mo after the surgery, at which time a second recheck CT scan and bloodwork revealed diffuse hepatopathy and peritoneal effusion. The dog was hospitalized 3 d after this recheck because of signs of acute abdomen with vomiting, melena, polyuria, and polydipsia. Cytology of liver fine-needle aspirates revealed marked pyogranulomatous inflammation with acid-fast rod bacteria in histiocytes; phylogenetic analysis of hsp65 PCR amplicons from that tissue identified sequences identical to Mycobacterium heckeshornense. No other bacteria were isolated on a routine bacterial culture of a liver swab. Hepatic mycobacteriosis was treated with long-term enrofloxacin, clarithromycin, and doxycycline. The dog improved slowly, and the liver enzymes returned to normal after 4 mo of treatment. This is the first reported case of M. heckeshornense infection in a dog. Diseases caused by non-tuberculous mycobacteria such as M. heckeshornense are generally not reportable due to low risk of transmission between and to humans, but the zoonotic potential warrants further research in the future. Key clinical message: Dogs without overt immunodeficiency can be at risk of M. heckeshornense infection and can develop life-threatening pathology affecting multiple organs. However, clinical resolution can be achieved even in a severely affected dog. If Mycobacterium is suspected, it is important to consult with diagnostic laboratories to ensure correct samples are obtained and correct analytical procedures are used., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Hepatic impairment (HI) trials are traditionally part of the clinical pharmacology development to assess the need for dose adaptation in people with impaired metabolic capacity due to their diseased liver. This review aimed at looking into the data from dedicated HI studies, cluster these data into various categories and connect the effect by HI with reported pharmacokinetics (PK) properties in order to identify patterns that may allow waiver, extrapolations, or adapted HI study designs. Based on a ratio ≥ 2 or ≤ 0.5 in AUC or Cmax between hepatically impaired participants/healthy controls these were considered "positive" or "negative". In case of more than one HI severity stratum per compound included in the HI trial, the comparison of the AUC ratios for mild, moderate, or severe HI were used to investigate the increase across HI categories. For the in total 436 hits, relevant PK information could be retrieved for 273 compounds of which 199 were categorized negative, 69 positive ups and 5 positive downs. Fourteen out of 69 compounds demonstrated a steep increase in the AUC ratios from mild to severe HI. Compounds demonstrating a steep increase typically had a high plasma protein binding of > 95%, high volume of distribution, lower absolute bioavailability, minor elimination via the kidneys, were predominantly metabolized by CYP3A4 or CYP2D6 and the majority of these compounds were substrates of OATP1B1. While for compounds with steep increase studies in all severity strata may be warranted they may also offer the potential to estimate the appropriate doses in an HI trial. On the other hand, for compounds with slow or no increase across HI severity strata, reduced HI trials may be justified, e.g. only testing PK in moderate HI., (© 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Xiaohua Funing Tang (XHFND) is a decoction formula of traditional Chinese medicine (TCM) and possesses the potential to manage chronic atrophic gastritis (CAG) with liver depression and spleen deficiency (LDSD), but the mechanisms were still unclear., Purpose: Our aim is to reveal the overall synergistic mechanisms of XHFND against CAG with LDSD., Methods: Based on a CAG rat model with LDSD, this study combined metabolomics, gut microbiota, and network pharmacology techniques to demonstrate the XHFND mechanisms with multiple components and targets., Results: Through the integration analysis of gut microbiome and metabolome using metorigin, we found that XHFND regulates arginine metabolism levels in the urea cycle by regulating the gut ecological environment and the host. The XHFND mainly promotes aspartate 1 metabolism by regulating the abundance of odoribacter, bacteroides, phocaeicola, lachnospire, and intestinimonas, intervened in the imbalance of arginine metabolism in CAG rats with LDSD, suppresses the pathogenic Th17 cell differentiation, and inhibits the gastric mucosa damage in rats. Through Cytoscape analysis of network pharmacology and metabolomics integration, we found that XHFND might regulate host phospholipid metabolism through PTEN and PIK3CA to inhibit the PI3K-AKT-TSC axis and then inhibit mTORC1 to control arginine metabolism in the urea cycle and produce polyamines, thereby inhibiting the pathogenic Th17 cell differentiation and preventing rat gastric mucosa damage. Intervention in arginine metabolism in the urea cycle is the primary pathway in which XHFND exerts its therapeutic effects. XHFND may mainly control the pathogenic Th17 cell differentiation in the gastric mucosa of model rats through the pathway., Conclusion: This study indicated that XHFND might intervene in treating CAG with LDSD from multiple levels and perspectives to suppress the pathogenic Th17 cell differentiation, which aligns with the characteristics of TCM treatment. This study presents experimental evidence for the clinical use of XHFND and promotes the development of drugs for the therapy of CAG with LDSD., Competing Interests: Declaration of competing interest We declare that we have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Enzymatic deficiency in Gaucher disease (GD) may induce oxidative stress. Vitamin E is the nature's most effective lipid-soluble antioxidant. This prospective clinical trial assessed the oxidant-antioxidant status in Egyptian patients with GD and the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy. Forty children and adolescents with GD on stable doses of enzyme replacement therapy (ERT) were enrolled. Abdominal ultrasonography and transient elastography were performed. Malondialdehyde (MDA), vitamin E, and antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx], and peroxiredoxin 2 [PRDX2]) were assessed. Patients were compared with 40 age- and sex-matched healthy controls. Patients with GD were randomized either to receive oral vitamin E for 6 months or not. All patients with GD had significantly higher MDA levels with lower levels of vitamin E and antioxidant enzymes compared with healthy controls (p < 0.001). Vitamin E and PRDX2 were negatively correlated to severity score index (SSI), lyso GL1, and MDA. After 6 months of vitamin E supplementation, SSI and liver and spleen volumes and liver stiffness were significantly lower. Lyso GL1 and MDA were significantly decreased post-vitamin E therapy while antioxidant enzymes were significantly higher compared with baseline levels and with patients without vitamin E therapy. Oxidative stress is related to disease severity in pediatric patients with GD. A 6-month vitamin E supplementation for those patients represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress, and improving outcomes., (© 2024 SSIEM.)

Sepsis is a potentially fatal disease that arises from an infection and is characterized by an uncontrolled immune system reaction. Global healthcare systems bear a heavy financial burden from treating sepsis. This study aimed to provide information on the effective properties of silver nanoparticles derived from pomegranate peel extract (P-AgNP) against sepsis-induced hepatic injury. P-AgNPs were spherical with a diameter of ~19 nm. The animals were placed into four groups, each with seven rats. Group 1 functioned as the control group, receiving only saline for 7 days. Group 2 received only P-AgNPs at a dose of 20 mg/kg. To induce sepsis, groups 3 and 4 were given an intraperitoneal injection of 200 mg/mL cecal slurry. Sixty min later, group 4 was given 20 mg/kg of P-AgNPs daily for 7 days. The concentrations of reduced glutathione, nitric oxide, lipid peroxidation, and superoxide dismutase in liver homogenate were measured to determine the oxidative status. In addition, enzyme activities (alanine aminotransferase, aspartate amino transferase, and alkaline phosphatase) were measured. Furthermore, we investigated the histological changes, immunohistochemical expression of nuclear factor-κB, and mRNA levels of IL1β, IL-6, TNF-α, Bax, BCl2, and Casp-3. P-AgNPs functioned as regulators in a sepsis model, successfully controlling altered gene expression. Following treatment, P-AgNPs improved tion and oxidative state, indicating a role in sepsis management. Based on our findings, we conclude that P-AgNPs have antioxidant activity and may be useful in preventing sepsis-induced liver inflammation, oxidative damage, and apoptosis. RESEARCH HIGHLIGHTS: Pomegranate peel-derived silver nanoparticles (P-AgNPs) enhanced liver function and oxidative state in rats with sepsis-induced hepatic damage. P-AgNPs reduced oxidative stress and liver inflammation via regulating inflammatory and apoptotic gene expression. P-AgNPs enhanced liver enzyme activities, histological structure, and immunohistochemistry expression of nuclear factor-κB., (© 2024 Wiley Periodicals LLC.)

Liver diseases represent a formidable global health threat. Hesperidin, a flavonoid found in citrus fruits, is the source of diosmin (DS). The in vivo and in vitro investigations of the pharmacological effects of DS reveal that it exhibits tremendous beneficial effects, such as fighting against inflammation, oxidative stress, and fibrosis. These effects have been noticed in various disease models, emphasizing the potential therapeutic value of DS in tackling diverse pathological conditions. Interestingly, DS has promising liver-defense capabilities against a range of hepatic illnesses, such as radiation-induced hepatic injury, liver ischemia/reperfusion injury, alcoholic hepatic disease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Furthermore, DS demonstrates potential hepatoprotective effects against environmental toxins, such as heavy metals. DS activates PPAR-γ and Nrf2, leading to antioxidant effects that reduce oxidative stress. Moreover, DS suppresses NF-κB, NLRP3, MAPK activities, and cytokine production (TNF-α and IL-1β), resulting in inflammation suppression. These anti-inflammatory effects are attributed to the activation of PPAR-γ and Nrf2, which are NF-κB inhibitors. This review aims to comprehensively discuss the hepatoprotective capacity of DS, elucidating the underlying mechanisms and identifying several research avenues that warrant further exploration to ascertain the prospective clinical advantages of DS intake as a viable strategy for the treatment of hepatic illnesses., Competing Interests: Declarations. Ethical approval: Not applicable., (© 2024. The Author(s).)

Patients with diabetic are at a higher risk of developing hepatic disorders compared to non-diabetic individuals. This increased risk can be attributed to the diabetic environment, which triggers and exacerbates harmful pathways involved in both diabetic complications and hepatic disorders. Therefore, it is important to consider the use of antidiabetic agents that offer benefits beyond glycemic control and have positive effects on liver tissues. Glucagon-like peptide-1 (GLP-1) mimetics are a novel class of antidiabetic medications known for their potent blood sugar-lowering effects. Emerging evidence suggests that these drugs also have favorable effects on the liver. However, the precise effects and underlying mechanisms are not yet fully understood. In this review, we aim to provide a mechanistic perspective on the liver benefits of GLP-1 mimetics and outline the mediating mechanisms involved., Competing Interests: Declaration of competing interest The authors declare that have no conflict of interest in this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)