The autophagy-targeting compound V46 enhances antimicrobial responses to Mycobacteroides abscessus by activating transcription factor EB.

Mycobacteroides abscessus (Mabc) is a rapidly growing nontuberculous mycobacterium that poses a considerable challenge as a multidrug-resistant pathogen causing chronic human infection. Effective therapeutics that enhance protective immune responses to Mabc are urgently needed. This study introduces trans-3,5,4'-trimethoxystilbene (V46), a novel resveratrol analogue with autophagy-activating properties and antimicrobial activity against Mabc infection, including multidrug-resistant strains.

CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1).

TNF in Human Tuberculosis: A Double-Edged Sword.

TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection.

Toxoplasma gondii Induces Pyroptosis in Human Placental Trophoblast and Amniotic Cells by Inducing ROS Production and Activation of Cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 Inflammasome.

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms.

Itaconate family-based host-directed therapeutics for infections.

Itaconate is a crucial anti-infective and anti-inflammatory immunometabolite that accumulates upon disruption of the Krebs cycle in effector macrophages undergoing inflammatory stress. Esterified derivatives of itaconate (4-octyl itaconate and dimethyl itaconate) and its isomers (mesaconate and citraconate) are promising candidate drugs for inflammation and infection. Several itaconate family members participate in host defense, immune and metabolic modulation, and amelioration of infection, although opposite effects have also been reported.

Expression of cytokines and co-stimulatory molecules in the Toxoplasma gondii-infected dendritic cells of C57BL/6 and BALB/c mice.

Toxoplasma gondii is an intracellular protozoan parasite which can infect most warm-blooded animals and humans. Among the different mouse models, C57BL/6 mice are more susceptible to T. gondii infection compared to BALB/c mice, and this increased susceptibility has been attributed to various factors, including T-cell responses.

SIRT1 Promotes Host Protective Immunity against by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K/AKT Signalling Pathways.

Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K/AKT signalling pathways, promoting anti- responses.

Fenofibrate Exerts Anticancer Effects on Human Cervical Cancer HeLa Cells via Caspase-Dependent Apoptosis and Cell Cycle Arrest.

Objective: In the present study, we attempted to identify the effects of fenofibrate on human cervical cancer cells.

Methods: The cytotoxicity of fenofibrate in cervical cancer cells was determined by Cell Counting Kit-8. Immunoblotting assay was used to determine the protein expression of caspase-3, poly ADP-ribose polymerase cleavage, B-cell lymphoma 2 family protein expression, microtubule-associated protein 1A/1B-light chain 3 (LC3), as well as cyclins and cyclin-dependent kinases.

Trichomonas vaginalis induces apoptosis via ROS and ER stress response through ER-mitochondria crosstalk in SiHa cells.

Background: Trichomonas vaginalis causes lesions on the cervicovaginal mucosa in women; however, its pathogenesis remains unclear. We have investigated the involvement of the endoplasmic reticulum (ER) in the induction of apoptosis by T. vaginalis and its molecular mechanisms in human cervical cancer SiHa cells.

FAF1 downregulation by Toxoplasma gondii enables host IRF3 mobilization and promotes parasite growth.

Fas-associated factor 1 (FAF1) has gained a reputation as a member of the FAS death-inducing signalling complex. However, the role of FAF1 in the immunity response is not fully understood. Here, we report that, in the human retinal pigment epithelial (RPE) cell line ARPE-19 cells, FAF1 expression level was downregulated by Toxoplasma gondii infection, and PI3K/AKT inhibitors reversed T.

Silver nanoparticles induce apoptosis via -derived mitochondrial reactive oxygen species and endoplasmic reticulum stress in colorectal cancer cells.

To investigate the anticancer mechanisms of silver nanoparticles (AgNPs) in colorectal cancer. Anticancer effects of AgNPs were determined in colorectal cancer HCT116 cells and xenograft mice using cellular and molecular methods. AgNPs induced mitochondrial reactive oxygen species production, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses through and led to HCT116 cell apoptosis.

Adherence of to SiHa Cells is Inhibited by Diphenyleneiodonium.

Microbial adhesion is critical for parasitic infection and colonization of host cells. To study the host-parasite interaction in vitro, we established a flow cytometry-based assay to measure the adherence of to epithelial cell line SiHa. SiHa cells and were detected as clearly separated, quantifiable populations by flow cytometry.

Involvement of endoplasmic reticulum stress response and IRE1-mediated ASK1/JNK/Mcl-1 pathways in silver nanoparticle-induced apoptosis of human retinal pigment epithelial cells.

Silver nanoparticles (AgNPs) have cytotoxic effects on various human cell types. The endoplasmic reticulum (ER) is very sensitive to cytotoxic damage. Retina tissue is easily affected by internal and external stimuli.

Inflammasome and Mitophagy Connection in Health and Disease.

The inflammasome is a large intracellular protein complex that activates inflammatory caspase-1 and induces the maturation of interleukin (IL)-1β and IL-18. Mitophagy plays an essential role in the maintenance of mitochondrial homeostasis during stress. Previous studies have indicated compelling evidence of the crosstalk between inflammasome and mitophagy.

The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii.

Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T.

Silver Nanoparticle-Induced Apoptosis in ARPE-19 Cells Is Inhibited by Pre-Infection Through Suppression of NOX4-Dependent ROS Generation.

Purpose: External and internal stimuli easily affect the retina. Studies have shown that cells infected with are resistant to multiple inducers of apoptosis. Nanoparticles (NPs) have been widely used in biomedical fields; however, little is known about cytotoxicity caused by NPs in the retina and the modulators that inhibit nanotoxicity.

VEGF Production Is Regulated by the AKT/ERK1/2 Signaling Pathway and Controls the Proliferation of in ARPE-19 Cells.

The retina is the primary site of infection in the eye, and choroidal neovascularization in ocular toxoplasmosis is one of the most important causes of visual impairment. Vascular endothelial growth factor (VEGF) is one of the key regulators of blood vessel development, however, little is known about the mechanisms of -induced VEGF production in ocular toxoplasmosis. Here, we investigate the effect of on VEGF production regulation in human retinal pigment epithelium ARPE-19 cells and attempted to unveil the underlying mechanism of this event by focusing on the interaction between parasite and the selected host intracellular signaling pathways.

4-Hydroxybenzaldehyde Restricts the Intracellular Growth of Toxoplasma gondii by Inducing SIRT1-Mediated Autophagy in Macrophages.

Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs).

RM, a novel resveratrol derivative, attenuates inflammatory responses induced by lipopolysaccharide via selectively increasing the Tollip protein in macrophages: A partial mechanism with therapeutic potential in an inflammatory setting.

Although the novel resveratrol derivative RM has therapeutic potential for the treatment of inflammatory bowel disease, little is currently known regarding the manner whereby RM regulates excessive inflammatory responses. In this study, we initially investigated the molecular mechanisms underlying the anti-inflammatory effects induced by RM in Toll-like receptor (TLR)-activated macrophages. Upon stimulation with lipopolysaccharide, we found that RM-treated activated macrophages down-regulated the increase in pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and IL-12p70), nitric oxide (NO) production, and activating interleukin-1 receptor-associated kinase 1 (IRAK-1) phosphorylation, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways.

Omega-3 Polyunsaturated Fatty Acids Prevent Infection by Inducing Autophagy via AMPK Activation.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms in infection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of -infected macrophages with DHA resulted in colocalization of parasitophorous vacuoles with autophagosomes and reduced intracellular survival of .

Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells.

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T.

Therapeutic Potential of Gamma-Irradiated Resveratrol in Ulcerative Colitis via the Anti-Inflammatory Activity and Differentiation of Tolerogenic Dendritic Cells.

Background/aims: New therapeutic strategies and the development of treatments against inflammatory bowel disease (IBD) require the initiation of immune tolerance and inhibition of excessive inflammation. Resveratrol, a polyphenolic compound, is a powerful immunosuppressor, but it can lead to apoptotic death of normal cells at high concentrations. When we induced a structural modification of resveratrol by gamma irradiation, we were able to investigate the potential tolerogenic and anti-inflammatory effect of a new radiolysis product (named γ-Res) during dendritic cell (DC) activation/differentiation.

AMPK-Targeted Effector Networks in Mycobacterial Infection.

AMP-activated protein kinase (AMPK), a key metabolic regulator, plays an essential role in the maintenance of energy balance in response to stress. Tuberculosis (TB), primarily caused by the pathogen (Mtb), remains one of the most important infectious diseases worldwide, characterized by both high incidence and mortality. Development of new preventive and therapeutic strategies against TB requires a profound understanding of the various host-pathogen interactions that occur during infection.

Protective effects of a traditional herbal extract from Stellaria dichotoma var. lanceolata against Mycobacterium abscessus infections.

Stellaria dichotoma var. lanceolata (SdLv), a member of the Caryophyllaceae, is a traditional herbal medicine that has been used to treat fever, night sweats, and malaria in East Asia. Inflammation plays an essential role in both host defense and pathogenesis during infection by diverse intracellular pathogens.