α7 Nicotinic acetylcholine receptor: a key receptor in the cholinergic anti-inflammatory pathway exerting an antidepressant effect.

Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

Molecular mechanisms of rapid-acting antidepressants: New perspectives for developing antidepressants.

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.

The application of extracellular vesicles in colorectal cancer metastasis and drug resistance: recent advances and trends.

Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed.

Study on the ozonation degradation of methylene blue enhanced by microchannel and ultrasound.

Azo dye-containing wastewater poses serious risks of environmental pollution because it is generally biologically toxic and resistant to conventional wastewater treatment methods. A novel degradation system integrating ozone, microchannel, and ultrasound was designed to effectively degrade azo dye-contaminated wastewater. The effects of discharge voltage of dielectric barrier discharge (DBD) reactor, liquid flow rate, microchannel width, ultrasonic power, initial pH, and reaction temperature on methylene blue (MB) decolorization were studied. A maximum MB decolorization efficiency of 92.7% was obtained in the ozone/microchannel/ultrasound (O3/MC/US) system with 14 min of treatment. In addition, the 14-min decolorization efficiency and TOC removal efficiency obtained in O3/MC/US system were increased by 12.6 and 6.5%, respectively, compared to those obtained in the pure O3 system. Based on the results of scavenging experiments, the combined effects of microchannel and ultrasound were proved to improve the contribution rate of hydroxyl radicals, thus improving the decolorization efficiency. The present work clearly illustrates that ozonation degradation can be effectively enhanced by microchannel and ultrasound, and also provides a feasible method for the treatment of organic wastewater.

LRP5 promotes cancer stem cell traits and chemoresistance in colorectal cancer.

The overactivation of canonical Wnt/ß-catenin pathway and the maintenance of cancer stem cells (CSCs) are essential for the onset and malignant progression of most human cancers. However, their regulatory mechanism in colorectal cancer (CRC) has not yet been well demonstrated. Low-density lipoprotein receptor-related protein 5 (LRP5) has been identified as an indispensable co-receptor with frizzled family members for the canonical Wnt/ß-catenin signal transduction. Herein, we show that activation of LRP5 gene promotes CSCs-like phenotypes, including tumorigenicity and drug resistance in CRC cells, through activating the canonical Wnt/ß-catenin and IL-6/STAT3 signalling pathways. Clinically, the expression of LRP5 is upregulated in human CRC tissues and closely associated with clinical stages of patients with CRC. Further analysis showed silencing of endogenous LRP5 gene is sufficient to suppress the CSCs-like phenotypes of CRC through inhibiting these two pathways. In conclusion, our findings not only reveal a regulatory cross-talk between canonical Wnt/ß-catenin signalling pathway, IL-6/STAT3 signalling pathway and CD133-related stemness that promote the malignant behaviour of CRC, but also provide a valuable target for the diagnosis and treatment of CRC.

The Protective Role of 4-Acetylarylquinolinol B in Different Pathological Processes.

Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of Antrodia cinnamomea, and has many biological functions, such as anti-inflammatory, antiproliferative, blood sugar reduction, antimetastasis, and vascular tone relaxation. In recent years, the increasing evidences have shown that 4-AAQB is involved in many diseases; however, the relevant mechanisms have not been fully clarified. This review aimed to clarify the improvement by 4-AAQB in different pathological processes, as well as the compound's molecular mechanisms, in order to provide a theoretical reference for future related research.

The Role of H2S Regulating NLRP3 Inflammasome in Diabetes.

Nucleotide-binding oligomeric domain (NOD)-like receptor protein 3 (NLRP3) is a recently discovered cytoplasmic multiprotein complex involved in inflammation. The NLRP3 inflammasome contains NLRP3, apoptosis-related specific protein (ASC) and precursor caspase-1. The NLRP3 inflammasome is involved in many diseases, including diabetes. H2S is a harmful gas with a rotten egg smell. Recently, it has been identified as the third gas signal molecule after nitric oxide and carbon monoxide. It has many biological functions and plays an important role in many diseases, including diabetes. In recent years, it has been reported that H2S regulation of the NLRP3 inflammasome contributes to a variety of diseases. However, the mechanism has not been fully understood. In this review, we summarized the recent role and mechanism of H2S in regulating the NLRP3 inflammasome in diabetes, in order to provide a theoretical basis for future research.

The Role of Autophagy and Pyroptosis in Liver Disorders.

Pyroptosis is a programmed cell death caused by inflammasomes, which can detect cell cytosolic contamination or disturbance. In pyroptosis, caspase-1 or caspase-11/4/5 is activated, cleaving gasdermin D to separate its N-terminal pore-forming domain (PFD). The oligomerization of PFD forms macropores in the membrane, resulting in swelling and membrane rupture. According to the different mechanisms, pyroptosis can be divided into three types: canonical pathway-mediated pyroptosis, non-canonical pathway-mediated pyroptosis, and caspase-3-induced pyroptosis. Pyroptosis has been reported to play an important role in many tissues and organs, including the liver. Autophagy is a highly conserved process of the eukaryotic cell cycle. It plays an important role in cell survival and maintenance by degrading organelles, proteins and macromolecules in the cytoplasm. Therefore, the dysfunction of this process is involved in a variety of pathological processes. In recent years, autophagy and pyroptosis and their interactions have been proven to play an important role in various physiological and pathological processes, and have gradually attracted more and more attention to become a research hotspot. Therefore, this review summarized the role of autophagy and pyroptosis in liver disorders, and analyzed the related mechanism to provide a basis for future research.

The Emerging Role of EVA1A in Different Types of Cancers.

Eva-1 homolog A (EVA1A), also known as transmembrane protein 166 (TMEM166) and regulator of programmed cell death, is an endoplasmic reticulum associated protein, which can play an important role in many diseases, including a variety of cancers, by regulating autophagy/apoptosis. However, the related mechanism, especially the role of EVA1A in cancers, has not been fully understood. In this review, we summarize the recent studies on the role of EVA1A in different types of cancers, including breast cancer, papillary thyroid cancer, non-small cell lung cancer, hepatocellular carcinoma, glioblastoma and pancreatic cancer, and analyze the relevant mechanisms to provide a theoretical basis for future related research.

Hydrogen Sulfide Plays an Important Role by Regulating Endoplasmic Reticulum Stress in Diabetes-Related Diseases.

Endoplasmic reticulum (ER) plays important roles in protein synthesis, protein folding and modification, lipid biosynthesis, calcium storage, and detoxification. ER homeostasis is destroyed by physiological and pharmacological stressors, resulting in the accumulation of misfolded proteins, which causes ER stress. More and more studies have shown that ER stress contributes to the pathogenesis of many diseases, such as diabetes, inflammation, neurodegenerative diseases, cancer, and autoimmune diseases. As a toxic gas, H2S has, in recent years, been considered the third most important gas signal molecule after NO and CO. H2S has been found to have many important physiological functions and to play an important role in many pathological and physiological processes. Recent evidence shows that H2S improves the body's defenses to many diseases, including diabetes, by regulating ER stress, but its mechanism has not yet been fully understood. We therefore reviewed recent studies of the role of H2S in improving diabetes-related diseases by regulating ER stress and carefully analyzed its mechanism in order to provide a theoretical reference for future research.

Flubendazole Plays an Important Anti-Tumor Role in Different Types of Cancers.

Flubendazole, belonging to benzimidazole, is a broad-spectrum insect repellent and has been repurposed as a promising anticancer drug. In recent years, many studies have shown that flubendazole plays an anti-tumor role in different types of cancers, including breast cancer, melanoma, prostate cancer, colorectal cancer, and lung cancer. Although the anti-tumor mechanism of flubendazole has been studied, it has not been fully understood. In this review, we summarized the recent studies regarding the anti-tumor effects of flubendazole in different types of cancers and analyzed the related mechanisms, in order to provide the theoretical reference for further studies in the future.

The Role of Endoplasmic Reticulum Stress and NLRP3 Inflammasome in Liver Disorders.

The endoplasmic reticulum (ER) is a key organelle responsible for the synthesis, modification, folding and assembly of proteins; calcium storage; and lipid synthesis. When ER homeostatic balance is disrupted by a variety of physiological and pathological factors-such as glucose deficiency, environmental toxins, Ca2+ level changes, etc.-ER stress can be induced. Abnormal ER stress can be involved in many diseases. NOD-like receptor family pyrin domain-containing 3 (NLRP3), an intracellular receptor, can perceive internal and external stimuli. It binds to apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 to assemble into a protein complex called the NLRP3 inflammasome. Evidence indicates that ER stress and the NLRP3 inflammasome participate in many pathological processes; however, the exact mechanism remains to be understood. In this review, we summarized the role of ER stress and the NLRP3 inflammasome in liver disorders and analyzed the mechanisms, to provide references for future related research.

The Role of Hydrogen Sulfide Regulation of Autophagy in Liver Disorders.

Autophagy is a complex process of degradation of senescent or dysfunctional organelles in cells. Dysfunctional autophagy is associated with many diseases such as cancers, immune dysfunction, and aging. Hydrogen sulfide (H2S) is considered to be the third gas signal molecule after nitrous oxide and carbon monoxide. In recent years, H2S has been found to have a variety of important biological functions, and plays an important role in a variety of physiological and pathological processes. In this review, we review the recent role and mechanism of H2S in regulating autophagy in liver disorders, in order to provide a basis for further research in the future.

Exogenous Hydrogen Sulfide Plays an Important Role by Regulating Autophagy in Diabetic-Related Diseases.

Autophagy is a vital cell mechanism which plays an important role in many physiological processes including clearing long-lived, accumulated and misfolded proteins, removing damaged organelles and regulating growth and aging. Autophagy also participates in a variety of biological functions, such as development, cell differentiation, resistance to pathogens and nutritional hunger. Recently, autophagy has been reported to be involved in diabetes, but the mechanism is not fully understood. Hydrogen sulfide (H2S) is a colorless, water-soluble, flammable gas with the typical odor of rotten eggs, which has been known as a highly toxic gas for many years. However, it has been reported recently that H2S, together with nitric oxide and carbon monoxide, is an important gas signal transduction molecule. H2S has been reported to play a protective role in many diabetes-related diseases, but the mechanism is not fully clear. Recent studies indicate that H2S plays an important role by regulating autophagy in many diseases including cancer, tissue fibrosis diseases and glycometabolic diseases; however, the related mechanism has not been fully studied. In this review, we summarize recent research on the role of H2S in regulating autophagy in diabetic-related diseases to provide references for future related research.

The Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury.

Ischemia/reperfusion (I/R) injury is characterized by a limited blood supply to organs, followed by the restoration of blood flow and reoxygenation. In addition to ischemia, blood flow recovery can also lead to very harmful injury, especially inflammatory injury. Autophagy refers to the transport of cellular materials to the lysosomes for degradation, leading to the conversion of cellular components and offering energy and macromolecular precursors. It can maintain the balance of synthesis, decomposition and reuse of the intracellular components, and participate in many physiological processes and diseases. Inflammasomes are a kind of protein complex. Under physiological and pathological conditions, as the cellular innate immune signal receptors, inflammasomes sense pathogens to trigger an inflammatory response. TheNLRP3 inflammasome is the most deeply studied inflammasome and is composed of NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Its activation triggers the cleavage of pro-interleukin (IL)-1ß and pro-IL-18 mediated by caspase-1 and promotes a further inflammatory process. Studies have shown that autophagy and the NLRP3 inflammasome play an important role in the process of I/R injury, but the relevant mechanisms have not been fully explained, especially how the interaction between autophagy and the NLRP3 inflammasome participates in I/R injury, which remains to be further studied. Therefore, we reviewed the recent studies about the interplay between autophagy and the NLRP3 inflammasome in I/R injury and analyzed the mechanisms to provide the theoretical references for further research in the future.

The Complex Interplay between Autophagy and NLRP3 Inflammasome in Renal Diseases.

Autophagy is a highly conserved process of the eukaryotic cell cycle. It plays an important role in the survival and maintenance of cells by degrading organelles, proteins, and macromolecules in the cytoplasm and the circulation of degraded products. The dysfunction of autophagy can lead to the pathology of many human diseases. The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome belongs to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs) and can induce caspase-1 activation, thus leading to the maturation and secretion of interleukin-1beta (IL-1ß) and IL-18. It has been reported that the interplay between autophagy and NLRP3 inflammasome is involved in many diseases, including renal diseases. In this review, the interplay between autophagy and the NLRP3 inflammasome and the mechanisms in renal diseases are explored to provide ideas for relevant basic research in the future.

Fluorescent carbon dots as an efficient siRNA nanocarrier for its interference therapy in gastric cancer cells.

BACKGROUND: Fluorescent carbon dots (Cdots) have attracted increasing attention due to their potential applications in sensing, catalysis, and biomedicine. Currently, intensive research has been concentrated on the synthesis and imaging-guided therapy of these benign photoluminescent materials. Meanwhile, Cdots have been explored as nonviral vector for nucleic acid or drug delivery by chemical modification on purpose. RESULTS: We have developed a microwave assisted one-step synthesis of Cdots with citric acid as carbon source and tryptophan (Trp) as both nitrogen source and passivation agent. The Cdots with uniform size show superior water solubility, excellent biocompatibility, and high quantum yield. Afterwards, the PEI (polyethylenimine)-adsorbed Cdots nanoparticles (Cdots@PEI) were applied to deliver Survivin siRNA into human gastric cancer cell line MGC-803. The results have confirmed the nanocarrier exhibited excellent biocompatibility and a significant increase in cellular delivery of siRNA, inducing efficient knockdown for Survivin protein to 6.1%. In addition, PEI@Cdots complexes mediated Survivin silencing, the arrested cell cycle progression in G1 phase as well as cell apoptosis was observed. CONCLUSION: The Cdots-based and PEI-adsorbed complexes both as imaging agents and siRNA nanocarriers have been developed for Survivin siRNA delivery. And the results indicate that Cdots-based nanocarriers could be utilized in a broad range of siRNA delivery systems for cancer therapy.

Triptolide regulates neutrophil function through the Hippo signaling pathway to alleviate rheumatoid arthritis disease progression.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammatory changes in the joints, the etiology of which is unclear. It is now well established that regulated cell death (RCD) and migration of neutrophils play an important role in the pathogenesis of RA. Tripterygium wilfordii Hook.f (TwHF) is a total saponin extracted from the root of Tripterygium wilfordii Hook.f, a plant of the family Wesleyanaceae, which has strong anti-inflammatory and immunomodulatory effects and has been used as a basic drug in the clinical treatment of RA. Despite the good efficacy of TwHF treatment, the mechanism of action of TwHF remains unclear. Several studies have demonstrated that the drug tripterygium glycosides, in which TwHF is the main ingredient, has achieved excellent efficacy in the clinical treatment of RA. Investigations have also found that TwHF can affect cellular RCD, cell migration, cell proliferation, and the apoptosis-related Hippo signaling pathway. In this study, we first analyzed the RCD and migration differences of neutrophils in patients with RA through network pharmacology and transcriptome analysis. Subsequently, we used electron microscopy, immunofluorescence, and other methods to identify the RCD phenotype of neutrophils. In collagen-induced arthritis (CIA) model, we demonstrated that Triptolide (the main active ingredient in TwHF) could alleviate the progression of arthritis by reducing the bone destruction and the infiltration of neutrophils. Furthermore, in vitro experiments showed that Triptolide induced neutrophil apoptosis, inhibited the formation of neutrophil extracellular traps (NETs), and impeded the neutrophil migration process in a Hippo pathway-dependent manner. Taken together, these findings indicate that Triptolide has potential for treating RA and provide theoretical support for the clinical application of TwHF, as a traditional Chinese medicine, in RA.

Bromide-mediated, C2-selective, and oxygenative alkylation of pyridinium salts using alkenes and molecular oxygen.

Herein, we report a bromide-mediated, C2-selective, and oxygenative alkylation of pyridinium salts using alkenes and O2 for the synthesis of important ß-2-pyridyl ketones. Notably, a quaternary carbon center was successfully installed at the C2-position of pyridine and the resulting C2-substituents were highly functionalized. The intermediary cycloadduct was isolated and further transformed into the desired product, which indicated that this three-component reaction underwent a reaction cascade including dearomative cycloaddition and rearomative ring-opening oxygenation. Finally, the bromide-mediated mechanism was discussed and active Br(I) species were proposed to be generated in situ and promote the rearomative ring-opening oxygenation by halogen bond-assisted electron transfer.

The role of NLRP3 inflammasome in hepatocellular carcinoma.

Inflammasomes play an important role in innate immunity. As a signal platform, they deal with the excessive pathogenic products and cellular products related to stress and injury. So far, the best studied and most characteristic inflammasome is the NLR-family pyrin domain-containing protein 3(NLRP3) inflammasome, which is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. The formation of NLRP3 inflammasome complexes results in the activation of caspase-1, the maturation of interleukin (IL)-1ß and IL-18, and pyroptosis. Many studies have demonstrated that NLRP3 inflammasome not only participates in tumorigenesis, but also plays a protective role in some cancers. Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Currently, due to the lack of effective treatment methods for HCC, the therapeutic effect of HCC has not been ideal. Therefore, it is particularly urgent to explore the pathogenesis of HCC and find its effective treatment methods. The increasing evidences indicate that NLRP3 inflammasome plays a vital role in HCC, however, the related mechanisms are not fully understood. Hence, we focused on the recent progress about the role of NLRP3 inflammasome in HCC, and analyzed the relevant mechanisms in detail to provide reference for the future in-depth researches.