RESUMO
BACKGROUND: Chronic hepatitis B (CHB) infection is still a major global public health problem, with nearly two billion patients. Although current antiviral drugs can inhibit viral replication and reduce hepatitis B virus (HBV) related complications, it is difficult to achieve clinical endpoints due to drug resistance. SUMMARY: Immune checkpoint inhibitors (ICIs) are an important strategy to reverse T-cell exhaustion, and rebuilding an effective functional T-cell response is a promising immunomodulatory approach for CHB patients. However, ICIs may lead to viral reactivation or immune-related adverse effects. There are still many controversies in the application of ICIs in treating patients with CHB. KEY MESSAGES: This article reviews the research progress of ICIs in CHB infection and related issues. The goal of this paper was to summarize the possible impact of new therapies for CHB with the aim of reducing potential clinical risks.
Assuntos
Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1/uso terapêutico , Vírus da Hepatite B/fisiologia , Linfócitos T CD8-Positivos , Antivirais/uso terapêutico , Antivirais/farmacologiaRESUMO
The antimicrobial peptides (AMPs) are a group of unique naturally occurring anti-microbial compounds with around 50 amino acids. It represents promising therapeutic agents to the infectious disease without concerning about drug resistance. However, commercial development of these peptides for even the simplest application has been hindered by the limitations of sources, instability, toxicity and bioavailability. To improve the properties of the artificial synthesized AMPs, the modification and design are the hotspots of the AMPs research. In fact, more than half of the known AMPs are naturally modified. In this review, two types of modification strategies, biochemical modification and chemical modification were summarized. Although, the chemical modification is versatile and direct, the manufacturing cost is greatly increased compared to the antibiotics. With the recent progress of the protein modification enzyme, the biochemical modification of the antimicrobial peptide followed by heterologous expression has great application prospects.
Assuntos
Antibacterianos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Desenho de Fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Apoptose/efeitos dos fármacos , Doenças Transmissíveis/tratamento farmacológico , HumanosRESUMO
To elucidate how antigen exposure and selection shape the porcine antibody repertoires, we investigated the immunoglobulin lambda light chain (IGL) gene repertoires of the binary cross-bred (Yorkshire×Landrace) pig at different developmental stages, pre-suckle neonate (0days), wean piglet (35days) and growing pig (75days) under normal farming conditions. Immunoglobulin lambda light transcript (IGLV-J-C) clones of the peripheral blood mononuclear cells (PBMCs) from these different developmental stages were assessed for IGL combination, junction and sequence diversity. Previous research has revealed that IGLV8 plays a major role in immunity during the early fetus stage and that IGLV3 accounts for 30% of the neonatal IGLV repertoires. Here, we found that the antibody profile exhibited salient features at different stages. The usage of the IGLV3-3 subclass gradually decreased during development, in contrast, the utilization of IGLV8 (IGLV8-10, IGLV8-13 and IGLV8-18), which started in the fetal stage, has increased in the growing stage. Moreover, the junction diversity, as measured by the IGLV hypervariable complementarity determining region 3 (CDR3L) lengths, was constant during the different stages. The complete junction mutation ratio clearly increased in the growing pig compared to that in the younger pig. Our data provide new insights into the postnatal porcine IGLV repertoires maturation which can lay the foundation for porcine antibody gene research.