Analysis of Immunometabolic Profiles in Patients With Chronic Drug-Induced Liver Injury and Validation in Mice to Reveal Potential Mechanisms.

Background: The mechanism underlying chronic drug-induced liver injury (DILI) remains unclear. Immune activation is a common feature of DILI progression and is closely associated with metabolism. We explored the immunometabolic profile of chronic DILI and the potential mechanism of chronic DILI progression.

[ Formula improves liver function of mice with acute-on-chronic liver failure by inhibiting excessive activation of the cGAS-STING signaling pathway].

Objectives: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice.

Methods: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (6). In all but the control group, the mice were treated with CCl to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF.

[Integrated evidence chain: a new strategy and methodology for effectiveness e valuation of traditional Chinese medicines].

The evaluation of the effectiveness of traditional Chinese medicine(TCM) has long been a "bottleneck" issue that restricts the healthy development and internationalization of TCM. This article systematically analyzes the differences in diagnostic and treatment principles, material composition, new drug development pathways, efficacy cognition, and evaluation methodology between Chinese and Western medicine from the underlying logic of medical perspective. On this basis, it integrates the evidence elements of clinical experience, experimental research, and clinical trials, and for the first time proposes and establishes a new strategy and methodology for the evaluation of the effectiveness of TCM: the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(iEC-Eff), forming an integrated evaluation and confirmation model of "clinical experience-experimental research-clinical trial" for the effectiveness of TCM.

Inhibition of hepatitis B virus through PPAR-JAK/STAT pathway modulation by electroacupuncture and tenofovir disoproxil fumarate combination therapy.

Background: Acupuncture combined with nucleos(t)ide analogues (NAs) has shown promise in treating chronic hepatitis B (CHB), though mechanisms remain unclear. This study evaluates the antiviral effects of combining acupuncture with NAs against hepatitis B virus (HBV) and explores underlying mechanisms.

Methods: The HBV-infected mouse model, established using the high-pressure hydrodynamic method, was divided into three groups: normal saline (NS), tenofovir disoproxil fumarate (TF), and electroacupuncture combined with TF (E_T), n = 6.

Pentagalloylglucose alleviates acetaminophen-induced acute liver injury by modulating inflammation via cGAS-STING pathway.

Background: The cGAS-STING pathway is an important component of the innate immune system and plays significant role in acetaminophen-induced liver injury (AILI). Pentagalloylglucose (PGG) is a natural polyphenolic compound with various beneficial effects, including anti-cancer, antioxidant, anti-inflammatory, and liver-protective properties; however, whether it can be used for the treatment of AILI and the specific mechanism remain unclear.

Materials And Methods: A cell culture model was created to study the effect of PGG on cGAS-STING pathway activation using various techniques including western blotting (WB), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and immunoprecipitation (IP).

An Experimental Animal Study: Electroacupuncture Facilitates Antiviral Immunity Against Hepatitis B Virus Through the IFN-γ/JAK/STAT Axis.

Background: Chronic hepatitis B (CHB) remains a global health challenge, necessitating innovative therapeutic strategies. Enhancing the body's immune response against the hepatitis B virus (HBV) emerges as a fundamental strategy for achieving a functional cure. While acupuncture has shown potential in immune modulation, its specific anti-HBV effects are not well understood.

Protective effects of Nogo-B deficiency in NAFLD mice and its multiomics analysis of gut microbiology and metabolism.

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver ailment that can lead to serious conditions such as cirrhosis and hepatocellular carcinoma. Hepatic Nogo-B regulates glucose and lipid metabolism, and its inhibition has been shown to be protective against metabolic syndrome. Increasing evidence suggests that imbalances in the gut microbiota (GM) and lipid metabolism disorders are significant contributors to NAFLD progression.

Schisandrin C enhances type I IFN response activation to reduce tumor growth and sensitize chemotherapy through antitumor immunity.

With the advancing comprehension of immunology, an increasing number of immunotherapies are being explored and implemented in the field of cancer treatment. The cGAS-STING pathway, a crucial element of the innate immune response, has been identified as pivotal in cancer immunotherapy. We evaluated the antitumor effects of lignan component Schisandrin C (SC) in 4T1 and MC38 tumor-bearing mice, and studied the enhancing effects of SC on the cGAS-STING pathway and antitumor immunity through RNA sequencing, qRT-PCR, and flow cytometry.

Dipeptide PA3264 derived from rare and endangered Squama Manis is a novel bioactive peptide for the treatment of triple-negative breast cancer.

Background: Squama Manis is a valuable traditional Chinese medicine with a long history of medicinal use in the treatment of breast-related diseases. However, owing to the excessive exploitation and utilization of the resources, Squama Manis has been included in the list of rare and endangered wild animals. The conservation of the resources of Squama Manis and continuing its clinical application has become an urgent problem, and the search for small-molecule substitutes for Squama Manis is an effective way to achieve this goal.

Shuangdan Jiedu Decoction improved LPS-induced acute lung injury by regulating both cGAS-STING pathway and inflammasome.

Ethnopharmacological Relevance: Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear.

Aim Of The Study: The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting.

Materials And Methods: We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them.

Total tanshinones ameliorates cGAS-STING-mediated inflammatory and autoimmune diseases by affecting STING-IRF3 binding.

Background: An important signaling pathway connecting illness and natural immunity is the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, but aberrant activation of this pathway is associated with the development of autoimmune and inflammatory diseases. Hence, targeted inhibition of the activation of the cGAS-STING pathway is potentially valuable in the treatment of disease. The primary active component of Salvia miltiorrhiza is total tanshinone (TTN).

New compatible pair of TCM: Paeoniae Radix Alba effectively alleviate Psoraleae Fructus-induced liver injury by suppressing NLRP3 inflammasome activation.

Objective: Drug-induced liver injury (DILI), a type of acute inflammation, has sparked significant concern owing to its unpredictability and severity. Psoraleae Fructus (PF), an edible Chinese herb widely used in traditional Chinese medicine (TCM), causes liver injury. Therefore, the elucidation of the mechanism underlying PF-induced liver injury and the search for more effective means of detoxification using herbal compatibility has become an urgent issue.

PROTAC technology: From drug development to probe technology for target deconvolution.

Drug development remains a critical focus within the global pharmaceutical industry. To date, more than 80 % of disease targets are considered difficult to target. The emergence of PROTAC technology has, to some extent, alleviated this challenge.

Amplifying protection against acute lung injury: Targeting both inflammasome and cGAS-STING pathway by drug pair.

Objective: Acute lung injury (ALI) is characterized by inflammation and currently lacks an efficacious pharmacological intervention. The medicine combination of (LJF) and (FF) demonstrates combined properties in its anti-infective, anti-inflammatory, and therapeutic effects, particularly in alleviating respiratory symptoms. In previous studies, Chinese medicine has shown promising efficacy in lipopolysaccharides (LPS)-induced ALI.

Anoectochilus roxburghii polysaccharide reduces D-GalN/LPS-induced acute liver injury by regulating the activation of multiple inflammasomes.

Background: Acute liver injury (ALI) is a serious syndrome with a high mortality rate due to viral infection, toxic exposure, and autoimmunity, and its severity can range from mildly elevated liver enzymes to severe liver failure. Activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome is closely associated with the development of ALI, and the search for an inhibitor targeting this pathway may be a novel therapeutic option. Anoectochilus roxburghii polysaccharide (ARP) is a biologically active ingredient extracted from Anoectochilus roxburghii with immunomodulatory, antioxidant, and anti-inflammatory bioactivities and pharmacological effects.

polysaccharides ameliorates cecal ligation and puncture-induced sepsis by inhibiting the cGAS-STING signaling pathway.

() is an ancient and widely used traditional Chinese medicine with good efficacy in clearing heat and detoxifying action. Studies suggest that Polysaccharides (GUP), one of the major components of has anti-inflammatory, anti-cancer and hepatoprotective effects., but its exact molecular mechanism has not been explored in depth.

Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.

Objective: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma.

Methods: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells.

Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-β1/Smad signaling pathway.

Objective: Breast cancer is a malignant tumor with high invasion and metastasis. TGF-β1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity.

Tryptanthrin suppresses multiple inflammasome activation to regulate NASH progression by targeting ASC protein.

Background: The adaptor protein apoptosis-associated speck-like protein (ASC) containing a caspase recruitment domain (CARD) can be activated through pyrin domain (PYD) interactions between sensors and ASC, and through CARD interactions between caspase-1 and ASC. Although the majority of ternary inflammasome complexes depend on ASC, drugs targeting ASC protein remain scarce. After screening natural compounds from Isatidis Radixin, we found that tryptanthrin (TPR) could inhibit NLRP3-induced IL-1β and caspase-1 production, but the underlying anti-inflammatory mechanisms remain to be elucidated.

[Mechanism of total glucosides of White Paeony Capsules in ameliorating acute lung injury based on NLRP3 inflammasome].

This study deciphered the ameliorating effect and molecular mechanism of the total glucosides of White Paeony Capsules(TGP) in the treatment of mice model with acute lung injury(ALI) via NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway of the inflammasome. The study established an inflammasome activation model of primed bone marrow-derived macrophages(BMDMs), and its molecular mechanism was investigated by Western blot(WB), immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA), and flow cytometry. C57BL/6J mice were randomly divided into a blank control group, a TGP group, a model group(LPS group), LPS+low-and high-dose TGP groups, LPS+MCC950 group, and LPS+MCC950+TGP group, with eight mice per group.

Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction.

In the realm of autoimmune and inflammatory diseases, the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway has been thoroughly investigated and established. Despite this, the clinical approval of drugs targeting the cGAS-STING pathway has been limited. The Total glucosides of paeony (TGP) is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis (RA), emerged as a subject of our study.

Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain.

Objective: A typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory.

Methods: A patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the (HILI Guidelines).

Results: Clinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis.