Dark tea ameliorates liver fibrosis via FXR/TGR5-mediated intestinal permeability and liver sinusoidal capillarization.

Ethnopharmacological Relevance: Dark tea, a post-fermented tea, has traditionally been used to regulate liver disorders. As an ethnomedicinal plant, its efficacy in alleviating chronic liver disease has been demonstrated.

Aim Of The Study: This study explored the protective effect and potential mechanism of dark tea extract (DTE) against hepatic fibrosis.

TLR3-mediated NET formation and macrophage activation in acute liver failure: Targeting IL-36 signaling to attenuate inflammatory drivers.

Background: Acute liver failure (ALF), characterized by inflammation-mediated hepatocyte dysfunction, poses a significant global health burden. Although neutrophils and macrophages are central to driving inflammatory responses in ALF, the molecular mechanisms governing IL-36-driven inflammation in toll-like receptor 3 (TLR3)-mediated NETosis and macrophage activation remain poorly understood. This study systematically delineates wherein TLR3 activation induces IL-36 hyperactivation and NETosis, which cooperatively trigger macrophage activation to accelerate ALF progression.

Food additive β-caryophyllene mitigates alcoholic steatohepatitis by dual modulation of inflammation and lipid metabolism: a diet-based intervention strategy.

Alcoholic steatohepatitis (ASH) represents excessive lipid accumulation and inflammatory infiltration in the spectrum of alcohol-associated liver diseases (ALDs). Unfortunately, currently, there are no FDA-approved drugs for the treatment of ASH. Thus, this study was aimed at demonstrating the practicability of β-caryophyllene (BCP), an FDA-approved food flavoring agent, against ASH and exploring its underlying mechanisms related to lipid metabolism regulation and inflammation.

Ginseng and Platycodon grandiflorum ameliorated pulmonary fibrosis and inflammation targeting TLR4-P2X7r/NLRP3 signaling pathway.

Ethnopharmacological Relevance: Ginseng and Platycodon grandiflorum (Jacq.) A. DC.

Imidazole-Based ALK5 Inhibitor Attenuates TGF-β/Smad-Mediated Hepatic Stellate Cell Activation and Hepatic Fibrogenesis.

Liver fibrosis resulting from severe liver damage is a major clinical problem for which effective pharmacological drugs and treatment strategies are lacking. TGF-β, a hallmark of liver fibrosis, has been shown to promote ALK5 phosphorylation in an activated state. Hence, the suppression of ALK5 signal transduction has emerged as a promising therapeutic strategy for the treatment of liver fibrosis.

Thiazole isomers as potential ALK5 inhibitors alleviate P2X7R-mediated inflammation during liver fibrosis.

Liver fibrosis is a critical precursor to the progression of cirrhosis and liver cancer. However, the development of precision therapies for this condition has been impeded by incompletely elucidated molecular mechanisms. Activin receptor like kinase 5 (ALK5), termed TGF-β type I receptor (TGF-βRI), has been identified as a promising therapeutic target for antifibrotic drug development.

Vincamine ameliorates hepatic fibrosis via inhibiting S100A4-mediated farnesoid X receptor activation: based on liver microenvironment and enterohepatic circulation dependence.

Background And Purpose: Vincamine has extensive biological and pharmaceutical activity. We examined the hepatoprotective effects and mechanisms by which vincamine suppresses hepatic fibrosis.

Experimental Approach: Hepatic stellate cells (HSCs), TGF-β stimulated, were cultured with either vincamine, farnesoid X receptor (NR1H4; FXR) agonist or antagonist.

The effect of carrier concentration on the electronic structure and magnetothermal properties of a two-dimensional VTe monolayer with a high Curie temperature.

Two-dimensional (2D) magnetic transition metal dichalcogenides have unique electronic properties, ferromagnetism, and tunable properties in low-dimensional systems. In this paper, the structural, electronic, and magnetic properties of the VTe monolayer under different carrier concentrations were investigated using first-principles calculations and Monte Carlo (MC) simulations. It is found that by introducing a suitable number of electrons, the VTe monolayer can undergo a transition from a semiconductor to a half-metal state, with 100% spin polarization.

Xanthene-based NIR organic phototheranostics agents: design strategies and biomedical applications.

Fluorescence imaging and phototherapy in the near-infrared window (NIR, 650-1700 nm) have attracted great attention for biomedical applications due to their minimal invasiveness, ultra-low photon scattering and high spatial-temporal precision. Among NIR emitting/absorbing organic dyes, xanthene derivatives with controllable molecular structures and optical properties, excellent fluorescence quantum yields, high molar absorption coefficients and remarkable chemical stability have been extensively studied and explored in the field of biological theranostics. The present study was aimed at providing a comprehensive summary of the progress in the development and design strategies of xanthene derivative fluorophores for advanced biological phototheranostics.

Optimizing the cumulative cisplatin dose for concurrent chemoradiotherapy beneficiaries among elderly nasopharyngeal carcinoma patients: a real world study.

This study aimed to find a safe and effective cumulative cisplatin dose (CCD) for concurrent chemoradiotherapy (CCRT) beneficiaries among elderly nasopharyngeal carcinoma (NPC) patients. A total of 765 elderly (≥ 60 years old) NPC patients treated with cisplatin-based CCRT and IMRT-alone from 2007 to 2018 were included in this study. RPA-generated risk stratification was used to identify CCRT beneficiaries.

Long-term Outcomes Following Individualized Primary Tumor Clinical Target Volume Delineation Based on Stepwise Spread Patterns of Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy.

Purpose: Our institution has developed an individualized elective primary tumor clinical target volume (CTVp) delineation protocol for nasopharyngeal carcinoma (NPC) based on stepwise tumor spread patterns in intensity modulated radiation therapy for over 10 years. Herein, we report the long-term efficacy and toxicities in patients with NPC treated under this protocol.

Methods And Materials: A total of 7262 patients with histologically proven nonmetastatic NPC treated with intensity modulated radiation therapy following this individualized delineation protocol were retrospectively evaluated.

Palmatine, an isoquinoline alkaloid from Phellodendron amurense Rupr., ameliorated gouty inflammation by inhibiting pyroptosis via NLRP3 inflammasome.

Ethnopharmacological Relevance: Palmatine (Pal), derived from Daemonorops margaritae (Hance) Becc and Phellodendron amurense Rupr. is a natural isoquinoline alkaloid widely used in clearing heat and drying dampness, purging the pathogenic fire and removing symptoms, detoxifying toxins and healing sores.

Aim Of The Study: Gout is a common metabolic inflammatory disease caused by the deposition of MSU crystals (MSU) in joints and non-articulation structures.

Dietary supplementation of pterostilbene, a major component in small berries, prevents alcohol-induced liver injury associated with lipid accumulation and inflammation.

Pterostilbene (PTE), a natural stilbene found in small berries, exhibits multiple pharmacological activities, particularly antioxidant and anti-inflammatory activities. This study explores the dietary supplementation of PTE to ameliorate acute and chronic alcohol-associated liver disease (ALD). C57BL/6 mice were administrated with PTE and subjected to acute or chronic alcohol stimulation.

Astilbin alleviates hepatic fibrosis through PXR-PINK1/Parkin pathway: A new strategy by regulating hepatic stellate cells-macrophage crosstalk.

Background: Astilbin (ATB), a natural dihydroflavonol compound, exists in many plants, processed and functional foods. ATB has multiple pharmacological effects, such as antioxidant, lipid-lowering, and hepatoprotective. However, its anti-hepatic fibrosis and mechanisms remain unclearly elucidated.

Casting NETs on Psoriasis: The modulation of inflammatory feedback targeting IL-36/IL-36R axis.

NETosis happens when neutrophils are activated and neutrophil extracellular traps (NETs) are formed synchronously, which is a hallmark of psoriasis. However, the specific trigger that drives NET formation and the distinct contents and interaction with interleukin-36 receptor (IL-36R) of NETs remain to be further elucidated. This work identified NET formation driven by toll-like receptor (TLR) 3 ligand (especially polyinosinic-polycytidylic acid (Poly(I:C)) were enhanced by purinergic receptor P2X ligand-gated ion channel 7 receptor (P2X7R) ligands (especially adenosine 5'-triphosphate (ATP)).

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis.

Diallyl disulfide, the bioactive component of Allium species, ameliorates pulmonary fibrosis by mediating the crosstalk of farnesoid X receptor and yes-associated protein 1 signaling pathway.

Environmental pollution, virus infection, allergens, and other factors may cause respiratory disease, which could be improved by dietary therapy. Allium species are common daily food seasoning and have high nutritional and medical value. Diallyl disulfide (DADS) is the major volatile oil compound of Allium species.

NETs contribute to psoriasiform skin inflammation: A novel therapeutic approach targeting IL-36 cytokines by a small molecule tetrahydroxystilbene glucoside.

Background: Psoriasis, a chronic immune-mediated skin disease with pathological features such as aberrant differentiation of keratinocytes, dermal-epidermal inflammation, and angiogenesis. 2,3,5,4'-Tetrahydroxy stilbene 2-Ο-β-d-glucoside (2354Glu) is a natural small molecule polyhydrostilbenes isolated from Polygonum multiglorum Thunb. The regulation of IL-36 subfamily has led to new pharmacologic strategies to reverse psoriasiform dermatitis.

Machine-Learning-Assisted Rational Design of Si─Rhodamine as Cathepsin-pH-Activated Probe for Accurate Fluorescence Navigation.

High-performance fluorescent probes stand as indispensable tools in fluorescence-guided imaging, and are crucial for precise delineation of focal tissue while minimizing unnecessary removal of healthy tissue. Herein, machine-learning-assisted strategy to investigate the current available xanthene dyes is first proposed, and a quantitative prediction model to guide the rational synthesis of novel fluorescent molecules with the desired pH responsivity is constructed. Two novel Si─rhodamine derivatives are successfully achieved and the cathepsin/pH sequentially activated probe Si─rhodamine─cathepsin-pH (SiR─CTS-pH) is constructed.

P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway.

Head and neck squamous cell carcinoma (HNSCC) can be defined as a deadly illness with a dismal prognosis in advanced stages. Therefore, we seek to examine P4HA2 expression and effect in HNSCC, along with the underlying mechanisms. This study utilized integrated bioinformatics analyses to evaluate the P4HA2 expression pattern, prognostic implication, and probable function in HNSCC.

Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti-cardiac fibrosis activity.

Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC) for phosphorylation of ALK5 of 16f (9.

A therapeutic strategy of parthenolide in improving imiquimod-induced psoriasis-like skin inflammation targeting IL-36/NETs through skin transdermal therapeutic system.

Background: Psoriasis is an inflammatory skin disease that occurs repeatedly over time. The natural product of sesquiterpene lactones, Parthenolide (Par), is isolated from Tanacetum parthenium L. (feverfew) which has significant effects on anti-inflammatory.

Angelica dahurica extract and its effective component bergapten alleviated hepatic fibrosis by activating FXR signaling pathway.

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A.

The thermoelectric properties of CdBr, CdI, and Janus CdBrI monolayers with low lattice thermal conductivity.

The investigation and development of high thermoelectric value materials has become a research hotspot in recent years. In this work, based on the density functional theory on the Perdew-Burke-Ernzerhof (GGA-PBE) level, the thermoelectric properties of transition metal halides CdBr, Janus CdBrI, and CdI monolayers have been systematically investigated using Boltzmann transport theory. The calculation of the electronic band structure shows that these three materials have indirect band gap semiconductor properties.