Discovery of novel biaryl urea derivatives against IL-1β release with low toxicity based on NEK7 inhibitor.

Aberrant activation of NLRP3 inflammasome is involved in various inflammatory diseases, making it a promising target for therapeutic intervention. NEK7, a member of the NIMA-related kinase (NEK) family, functions as a key NLRP3-binding protein and plays a crucial role in the regulation of NLRP3 inflammasome assembly and activation. Thus, disrupting NLRP3-NEK7 interactions by targeting NEK7 could be a promising strategy to inhibit the activation of NLRP3 inflammasome.

Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.

Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis.

Design, Synthesis, and Pharmacological Evaluation of Spiro[carbazole-3,3'-pyrrolidine] Derivatives as cGAS Inhibitors for Treatment of Acute Lung Injury.

Overactivation of cyclic GMP-AMP synthase (cGAS) is implicated in the occurrence of many inflammatory and autoimmune diseases, and inhibition of cGAS with a specific inhibitor has been proposed as a potential therapeutic strategy. However, only a few low-potency cGAS inhibitors have been reported, and few are suitable for clinical investigation. As a continuation of our structural optimization on the reported cGAS inhibitor (G140), we developed a series of spiro[carbazole-3,3'-pyrrolidine] derivatives bearing a unique 2-azaspiro[4.

RIPK1 inhibitor ameliorates pulmonary injury by modulating the function of neutrophils and vascular endothelial cells.

Acute lung injury (ALI) is an acute and progressive hypoxic respiratory failure that could progress to acute respiratory distress syndrome (ARDS) with a high mortality rate, thus immediate medical attention and supportive care are necessary. The pathophysiology of ALI is characterized by the disruption of the alveolar-capillary barrier and activation of neutrophils, leading to lung tissue damage. The receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising target for the treatment of multiple inflammatory diseases, but the role of RIPK1 in the ALI remains poorly understood.

Atranorin inhibits Zika virus infection in human glioblastoma cell line SNB-19 via targeting Zika virus envelope protein.

Background: Zika virus (ZIKV) is a single-stranded RNA flavivirus transmitted by mosquitoes. Its infection is associated with neurological complications such as neonatal microcephaly and adult Guillain-Barré syndrome, posing a serious threat to the health of people worldwide. Therefore, there is an urgent need to develop effective anti-ZIKV drugs.

Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.

Background: Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation.

Methods: Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates.

MiR-526b-3p enhances sensitivity of head and neck squamous cell carcinoma cells to radiotherapy via suppressing exosomal LAMP3-mediated autophagy.

Lysosomal associated membrane protein 3 (LAMP3) has been reported to be a tumour promoter in multiple cancer types by modulating tumour cell autophagy. However, the potential mechanism of LAMP3 in radio-resistance of head and neck squamous cell carcinoma (HNSCC) remains unknown. Therefore, our current study aims to detect the impacts of LAMP3 on the resistance of HNSCC cells to radiotherapy and meanwhile explore its functional mechanism.

Omni-media health education combined with nanodrug therapy on the creation of gastrointestinal microenvironment and the improvement of treatment compliance in patients with gastrointestinal tumors.

According to the randomization method, 82 patients can be divided into two groups, the control group and the study group, each with 41 patients participating in the investigation. All patients in the control group were cared for, and the study group used a health education model. The treatment mode of each group needs to adopt adherence, and it is necessary to maintain a healthy diet, smoking cessation and alcohol cessation, and regular review during the treatment of regular exercise and emotional regulation.

Atranorin inhibits NLRP3 inflammasome activation by targeting ASC and protects NLRP3 inflammasome-driven diseases.

Aberrant NLRP3 activation has been implicated in the pathogenesis of numerous inflammation-associated diseases. However, no small molecular inhibitor that directly targets NLRP3 inflammasome has been approved so far. In this study, we show that Atranorin (CHO), the secondary metabolites of lichen family, effectively prevents NLRP3 inflammasome activation in macrophages and dendritic cells.

Hemin protects UVB-induced skin damage through inhibiting keratinocytes apoptosis and reducing neutrophil infiltration.

Ultraviolet-B (UVB) exposure on the skin triggers apoptosis, oxidative stress and acute inflammatory responses, which eventually increases the risk of various skin disorders. Hemin, an iron-binding porphyrin, has been clinically used for porphyria treatment. However, whether hemin contributes to the skin protection against UVB injury remains to be elucidated.

A Retrospective Study of Chemotherapy and 3D-Image-Guided Afterloading Intracavitary Radiotherapy in Locally Advanced Cervical Cancer.

Aim: To investigate the value of neoadjuvant chemotherapy combined with 3D-image-guided afterloading intracavitary radiotherapy in locally advanced cervical cancer (LACC).

Methods: Patients with cervical cancer admitted to our hospital from January 1, 2020 to January 1, 2021 were retrieved and analyzed. Cases treated with neoadjuvant chemotherapy and 3D-image-guided afterloading intracavitary radiotherapy were assigned into the observation group (OG), while cases with neoadjuvant chemotherapy alone were assigned into the control group (CG).

Effect of 1 + N Extended Nursing Service on Functional Recovery of Colostomy Patients.

To many hospitals' management as well as to patients, the nursing service is one of the most important aspects. Many diseases like sugar, blood pressure, urine passage, and gas are a little bit dangerous to handle by patients themselves. The earlier stage models are unable to give good services to patients; therefore, an advanced JHE: Effect of 1 + N extended nursing service is necessary to crossover the above limitations.

Hemin protects against Zika virus infection by disrupting virus-endosome fusion.

Zika virus (ZIKV) is a flavivirus that causes severe neuropathology in newborns and adults. There is no ZIKV-specific treatment or preventative. Therefore, it is urgent to develop safe and effective anti-ZIKV agents.

Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation.

Purpose: Allergic asthma is a chronic inflammatory disorder with airway hyperresponsiveness and tissue remodeling as the main pathological characteristics. The etiology of asthma is relatively complicated, involving genetic susceptibility, epigenetic regulation, environmental factors, and immune imbalance. Colony stimulating factor 1 receptor (CSF-1R), highly expressed in myeloid monocytes, plays an important role in regulating inflammation.

Targeting PDE4 as a promising therapeutic strategy in chronic ulcerative colitis through modulating mucosal homeostasis.

Phosphodiesterase-4 (PDE4) functions as a catalyzing enzyme targeting hydrolyzation of intracellular cyclic adenosine monophosphate (cAMP) and inhibition of PDE4 has been proven to be a competitive strategy for dermatological and pulmonary inflammation. However, the pathological role of PDE4 and the therapeutic feasibility of PDE4 inhibitors in chronic ulcerative colitis (UC) are less clearly understood. This study introduced apremilast, a breakthrough in discovery of PDE4 inhibitors, to explore the therapeutic capacity in dextran sulfate sodium (DSS)-induced experimental murine chronic UC.

STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion.

Acute lung injury (ALI) is a common and devastating clinical disorder featured by excessive inflammatory responses. Stimulator of interferon genes (STING) is an indispensable molecule for regulating inflammation and immune response in multiple diseases, but the role of STING in the ALI pathogenesis is not well elucidated. In this study, we explored the molecular mechanisms of STING in regulating lipopolysaccharide (LPS)-induced lung injury.

Identification of phosphodiesterase-4 as the therapeutic target of arctigenin in alleviating psoriatic skin inflammation.

Introduction: Arctigenin, derived from Arctium lappa L., has multiple pharmacological activities, including immunoregulatory, anti-diabetic, anti-tumor, and neuroprotective effects. Nevertheless, the potential therapeutic target of arctigenin in modulating inflammation remains undefined.

Discovery of chiral N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones with anti-inflammatory activity from the nucleophilic addition reactions of the thiophenols and oxazolinium.

Herein we disclosed the novel nucleophilic addition reactions of the thiophenols and oxazolinium (DCZ0358) to produce N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones. After evaluating the anti-inflammatory activity in vitro, 2d was found having significant anti-TNFα activity. Through the amplified synthesis of 2d, four monomers (3a-b and 4a-d) were obtained by chiral separation of the product.

Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase.

The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyperinflammatory and autoimmune diseases, and the cGAS-targeting small molecule has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound (G140), we conducted a structural optimization on both its side chain and the central tricyclic core, leading to several subseries of compounds, including those unexpectedly cyclized complex ones.

Triptolide analog LLDT-8 ameliorates psoriasis-like dermatitis in BALB/c mice via suppressing the IL-36α signaling pathway.

Triptolide has shown a good immunosuppressive effect on autoimmune diseases. However, the toxicity limited its widely clinical practice. In this study, we investigated the effects and underlying mechanisms of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, on a murine psoriasis-like dermatitis model and related cell lines.

Blockade of TLRs-triggered macrophage activation by caffeic acid exerted protective effects on experimental ulcerative colitis.

Ulcerative colitis (UC) represents a relapsing and inflammatory bowel disease which is commonly linked with the communications between dysfunction of epithelium and mucosal immune responses. Though caffeic acid (CA) has numerous pharmacological capacities, whether CA demonstrates immunoregulation on the mucosal immune responses remains ill-defined. Herein, the present research demonstrated that CA could dramatically attenuate the mucosal inflammation, as evidenced by improving the disease severity, serum biochemical indexes, mucosal ulcerations, loss of epithelium and crypts, and secretion of inflammatory cytokines in the colonic homogenates and explants culture.

Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report.

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery.

Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.

Systemic sclerosis (SSc) is a life-threatening chronic connective tissue disease with the characteristics of skin fibrosis, vascular injury, and inflammatory infiltrations. Though inhibition of phosphodiesterase 4 (PDE4) has been turned out to be an effective strategy in suppressing inflammation through promoting the accumulation of intracellular cyclic adenosine monophosphate (cAMP), little is known about the functional modes of inhibiting PDE4 by apremilast on the process of SSc. The present research aimed to investigate the therapeutic effects and underlying mechanism of apremilast on SSc.

Heme supplementation ameliorates lupus nephritis through rectifying the disorder of splenocytes and alleviating renal inflammation and oxidative damage.

Heme is an important iron-containing porphyrin molecule expressed ubiquitously in organisms. Recently, this endogenous molecule has been widely reported to be involved in the pathogenesis of numerous diseases such as sepsis, atherosclerosis and inflammatory bowel disease. However, the role of heme during systemic lupus erythematosus (SLE) pathogenesis has not been previously evaluated.

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis.

Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC.