Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

20(S)- Protopanaxadiol saponins isolated from Panax notoginseng target the binding of HMGB1 to TLR4 against inflammation in experimental ulcerative colitis.

Ulcerative colitis (UC) has emerged as a global healthcare issue due to high prevalence and unsatisfying therapeutic measures. 20(S)- Protopanaxadiol saponins (PDS) from Panax notoginseng with anti-inflammatory properties is a potential anti-colitis agent. Herein, we explored the effects and mechanisms of PDS administration on experimental murine UC. Dextran sulfate sodium-induced murine UC model was employed to investigate anti-colitis effects of PDS, and associated mechanisms were further verified in HMGB1-exposed THP-1 macrophages. Results indicated that PDS administration exerted ameliorative effects against experimental UC. Moreover, PDS administration remarkably downregulated mRNA expressions and productions of related pro-inflammatory mediators, and reversed elevated expressions of proteins related to NLRP3 inflammasome after colitis induction. Furthermore, administration with PDS also suppressed the expression and translocation of HMGB1, interrupting the downstream TLR4/NF-κB pathway. In vitro, ginsenoside CK and 20(S)-protopanaxadiol, the metabolites of PDS, exhibited greater potential in anti-inflammation, and intervened with the TLR4-binding domain of HMGB1 predictably. Expectedly, ginsenoside CK and 20(S)-protopanaxadiol administrations inhibited the activation of TLR4/NF-κB/NLRP3 inflammasome pathway in HMGB1-exposed THP-1 macrophages. Summarily, PDS administration attenuated inflammatory injury in experimental colitis by blocking the binding of HMGB1 to TLR4, majorly attributed to the antagonistic efficacies of ginsenoside CK and 20(S)-protopanaxadiol.

Preclinical studies of licorice in ulcerative colitis: A systematic review with meta-analysis and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice, as a traditional Chinese herbal medicine, possessing the efficacies of invigorating spleen and replenishing qi, heat-clearing and detoxicating, phlegm-resolving and cough suppressant, relieving spasm and pain, and hamonizing actions of various medicines. AIM OF THE STUDY: The goal of this systematic review, which includes meta-analysis and network pharmacology in preclinical studies, is to investigate the multiple efficacies of licorice on ulcerative colitis (UC). MATERIALS AND METHODS: We searched several databases, e.g., Web of Science, Elsevier ScienceDirect and PubMed until Januanry 2022 for literature collection, and the Review Manager 5.3 was used to analyze the data. To synthesize the retrieved data, the fixed and random-effects models were utilized, respectively, and network pharmacology was applied to confirm the mechanisms. RESULTS: Based on the result of meta-analysis, it suggested that the treatments of licorice extract and its active compounds showed strong therpeutic effects, which not only reflected the declining histological score, a index of the colitis severity [SMD = -2.86, 95% CI (-3.65, -2.08); P < 0.00001], but also reversed colonic shortness [WMD = 1.67, 95% CI (1.16, 2.19); P < 0.00001] between experimental UC model and licorice-treatment groups. In addition, it suggested the significant reduction of TNF-α level [SMD = -2.70, 95% CI (-3.23, -2.16); P < 0.00001], which acted as a crucial role in inflammatory response. Furthermore, from the results of network pharmacology, it indicated that anti-inflammation, anti-oxidative stress, immunomodulatory effect and microbiota homeostasis were the predominant therapeutic mechanisms of licorice extract and its active compounds treating UC. CONCLUSION: This systematic review with meta-analysis and network pharmacology demonstrates an efficient role of licorice extract and its active compounds in preclinical studies of UC, which provides supporting evidence for clinical trial implementation. However, there exist some limitations, such as technique quality decificency, missed reports due to negative outcome, failure to calculate sample size, and the risk of bias.

Annexin V-Modified Platelet-Biomimetic Nanomedicine for Targeted Therapy of Acute Ischemic Stroke.

Thromboembolic stroke is typically characterized by the activation of platelets, resulting in thrombus in the cerebral vascular system, leading to high morbidity and mortality globally. Intravenous thrombolysis by tissue plasminogen activator (tPA) administration within 4.5 h from the onset of symptoms is providing a standard therapeutic strategy for ischemic stroke, but this reagent simultaneously shows potential serious adverse effects, e.g., hemorrhagic transformation. Herein, a novel delivery platform based on Annexin V and platelet membrane is developed for tPA (APLT-PA) to enhance targeting efficiency, therapeutic effects, and reduce the risk of intracerebral hemorrhage in acute ischemic stroke. After preparation by extrusion of platelet membrane and subsequent insertion of Annexin V to liposomes, APLT-PA exhibits a high targeting efficiency to activated platelet in vitro and thrombosis site in vivo, due to the binding to phosphatidylserine (PS) and activated platelet membrane proteins. One dose of APLT-PA leads to obvious thrombolysis and significant improvement of neurological function within 7 days in mice with photochemically induced acute ischemic stroke. This study provides a novel, safe platelet-biomimetic nanomedicine for precise thrombolytic treatment of acute ischemic stroke, and offers new theories for the design and exploitation of cell-mimetic nanomedicine for diverse biomedical applications.

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines.

Nuclear factor-kappa B (NF-κB) is a kind of multi-functional nuclear transcription factor involved in regulating gene transcription to influence pathological evolution of inflammatory and immune diseases. Numerous literature evidence that NF-κB pathway plays an essential role in pathogenic development of ulcerative colitis (UC). UC is a chronic non-specific inflammatory bowel disease, and until now, therapeutic agents for UC including aminosalicylates, corticosteroids and immune inhibitors still cannot exert satisfied effects on patients. In recent years, Chinese medicines suggest the advantages of alleviating symptoms and signs, decreasing side-effects and recurrence, whose one of mechanisms is related to regulation of NF-κB pathway. In this review, we categorize Chinese medicines according to their traditional therapeutic functions, and summarize the characteristics of Chinese medicines targeting NF-κB pathway in UC treatment. It indicates that 85 kinds of Chinese medicines' compounds and formulae can directly act on NF-κBp65; while 58 Chinese medicines' ingredients and formulae indirectly suppress NF-κBp65 by regulation of its upstream or other related pathways. Moreover, by the analysis of Chinese medicines' category based on their traditional functions, we conclude the category of dampness-drying and detoxificating medicine targeting NF-κB pathway accounts for primary status for amelioration of UC. Simultaneously, this review also contributes to the choices of Chinese medicine category and provides curative potential of Chinese medicines for clinical UC treatment.