Medical systems worldwide are being faced with a growing need to understand mechanisms behind the pathogenesis of heart failure (HF) that is considered as a leading cause of morbidity and mortality around the world. Elevated levels of inflammatory mediators have been identified in patients with HF, which are primarily manifestations of innate immune responses mediated by pattern recognition receptors (PRRs). Toll-like receptors (TLRs), which belong to PRRs, are subjected to the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to generate innate immune responses. More and more emerging data indicate that TLR signaling pathway molecules are involved in the progression of HF. Herein, we present new data with regard to the activation of TLRs in the failing heart, focusing on TLR2, TLR3, TLR4, and TLR9, and suggest the potential use of TLRs in target therapy.

Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent primary liver diseases worldwide and can develop into various conditions, ranging from simple steatosis, through non-alcoholic steatohepatitis (NASH), to fibrosis, and eventually cirrhosis and hepatocellular carcinoma. Nevertheless, there is no effective treatment for NAFLD due to the complicated etiology. Recently, activation of the NLPR3 inflammasome has been demonstrated to be a contributing factor in the development of NAFLD, particularly as a modulator of progression from initial hepatic steatosis to NASH. NLRP3 inflammasome, as a caspase-1 activation platform, is critical for processing key pro-inflammatory cytokines and pyroptosis. Various stimuli involved in NAFLD can activate the NLRP3 inflammasome, depending on the diverse cellular stresses that they cause. NLRP3 inflammasome-related inhibitors and agents for NAFLD treatment have been tested and demonstrated positive effects in experimental models. Meanwhile, some drugs have been applied in clinical studies, supporting this therapeutic approach. In this review, we discuss the activation, biological functions, and treatment targeting the NLRP3 inflammasome in the context of NAFLD progression. Specifically, we focus on the different types of therapeutic agents that can inhibit the NLRP3 inflammasome and summarize their pharmacological effectiveness for NAFLD treatment.

The inflammasome is a protein complex composed of a variety of proteins in cells and which participates in the innate immune response of the body. It can be activated by upstream signal regulation and plays an important role in pyroptosis, apoptosis, inflammation, tumor regulation, etc. In recent years, the number of metabolic syndrome patients with insulin resistance (IR) has increased year by year, and the inflammasome is closely related to the occurrence and development of metabolic diseases. The inflammasome can directly or indirectly affect conduction of the insulin signaling pathway, involvement the occurrence of IR and type 2 diabetes mellitus (T2DM). Moreover, various therapeutic agents also work through the inflammasome to treat with diabetes. This review focuses on the role of inflammasome on IR and T2DM, pointing out the association and utility value. Briefly, we have discussed the main inflammasomes, including NLRP1, NLRP3, NLRC4, NLRP6 and AIM2, as well as their structure, activation and regulation in IR were described in detail. Finally, we discussed the current therapeutic options-associated with inflammasome for the treatment of T2DM. Specially, the NLRP3-related therapeutic agents and options are widely developed. In summary, this article reviews the role of and research progress on the inflammasome in IR and T2DM.

Herpes simplex virus type 1 (HSV-1) is a globally widespread virus that causes and associates with a wide range of diseases, including herpes simplex encephalitis, herpes simplex keratitis, and herpes labialis. The interaction between HSV-1 and the host involves complex immune response mechanisms, including recognition of viral invasion, maintenance of latent infection, and triggering of reactivation. Antiviral therapy is the core treatment for HSV-1 infections. Meanwhile, vaccine development employs different strategies and methods, and several promising vaccine types have emerged, such as live attenuated, protein subunit, and nucleic acid vaccines, offering new possibilities for the prevention of HSV-1 infection. Moreover, HSV-1 can be modified into a therapeutic vector for gene therapy and tumour immunotherapy. This review provides an in-depth summary of HSV-1 infection-associated innate and adaptive immune responses, disease pathogenesis, current therapeutic approaches, recent advances in vaccine development, and vector therapy applications for cancer treatment. Through a systematic review of multiple aspects of HSV-1, this study aims to provide a comprehensive and detailed reference for the public on the prevention, control, and treatment of HSV-1.

Obesity-induced chronic inflammation is known to promote the development of many metabolic diseases, especially insulin resistance, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and atherosclerosis. Pattern recognition receptor-mediated inflammation is an important determinant for the initiation and progression of these metabolic diseases. Here, we review the major features of the current understanding with respect to obesity-related chronic inflammation in metabolic tissues, focus on Toll-like receptors and nucleotide-binding oligomerization domain-like receptors with an emphasis on how these receptors determine metabolic disease progression, and provide a summary on the development and progress of PRR antagonists for therapeutic intervention.

The testis is an immune privileged organ in which the tissue-specific cells have adopted effective innate immune functions against microbial pathogens. Toll-like receptors (TLRs) mediate innate immune response in the testis. The current study demonstrates that melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) initiate the testicular innate antiviral response. Both MDA5 and RIG-I are expressed in Leydig cells, and MDA5 is also expressed in spermatids. Polyinosinic-polycytidylic acid [poly(I:C)], a common agonist of MDA5 and RIG-I, significantly induces the expression of type I interferons (IFN-α/β) and antiviral proteins, including IFN-stimulated gene 15, 2'5'-oligoadenylate synthetase 1, and Mx GTPase 1, in primary TLR3-deficient (TLR3(-/-)) Leydig and germ cells. Moreover, major proinflammatory cytokines, including TNF-α and IL-6, are significantly up-regulated by poly(I:C) in these testicular cells. The poly(I:C)-induced innate antiviral response in the testicular cells is significantly reduced by knockdown of individual MDA5 and RIG-I using specific small interfering RNA. We also provide evidence that local injection of poly(I:C) induces antiviral response in the testis of TLR3(-/-) mice. These data provide novel insights into the mechanisms underlying testicular antiviral response.