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.

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.

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.

Berberine and its derivatives represent as the promising therapeutic agents for inflammatory disorders.

Berberine, with the skeleton of quaternary ammonium, has been considered as the well-defined natural product in treating multiple diseases, including inflammation, acute and chronic infection, autoimmune diseases, and diabetes. However, due to the low bioavailability and systemic exposure, broad clinical applications of berberine have been largely impeded. Numerous studies have been conducted to further explore the therapeutic capacities of berberine in preclinical and clinical trials.

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.

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.

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.

Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment.

Psoriasis is a kind of chronic inflammatory skin disorder, while the long-term use of conventional therapies for this disease are limited by severe adverse effects. Novel small molecules associated with new therapeutic mechanisms are greatly needed. It is known that phosphodiesterase 4 (PDE4) plays a central role in regulating inflammatory responses through hydrolyzing intracellular cyclic adenosine monophosphate (cAMP), making PDE4 to be an important target for the treatment of inflammatory diseases (e.

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.