@#Tumor immunotherapy is a therapeutic modality that uses immunological principles and methods to activate and enhance the body''s immune system to generate immune response for the removal of tumour cells. Many new immunotherapeutic agents have demonstrated effective anti-tumour capabilities, yet their clinical use is challenging due to the complex mechanisms of tumour immune escape. Meanwhile, these drugs would accumulate in different tissues and organs in the human body and be unable to achieve precise and specific targeting therapeutic effects, resulting in serious immune-related adverse effects, which greatly hinders the clinical potential of immunotherapy.Nanodrug delivery systems can deliver immunotherapeutic drugs to target tissues or specific immune cells precisely, thereby enhancing immune effects and reducing side effects.This paper reviews the research progress of nanodrug delivery systems in tumour immunotherapy in recent years based on the regulatory mechanism of the anti-tumour immune response, with a prospect of the challenges and development in this field.
Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.
The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
Animals , Male , Mice , Antioxidants/pharmacology , Apoptosis , Endoplasmic Reticulum Stress , Melatonin/pharmacology , Mice, Inbred C57BL , Nickel/adverse effects , Selenoproteins/genetics , Heart/drug effects
Due to its safety, convenience, low cost and good compliance, oral administration attracts lots of attention. However, the efficacy of many oral drugs is limited to their unsatisfactory bioavailability in the gastrointestinal tract. One of the critical and most overlooked factors is the symbiotic gut microbiota that can modulate the bioavailability of oral drugs by participating in the biotransformation of oral drugs, influencing the drug transport process and altering some gastrointestinal properties. In this review, we summarized the existing research investigating the possible relationship between the gut microbiota and the bioavailability of oral drugs, which may provide great ideas and useful instructions for the design of novel drug delivery systems or the achievement of personalized medicine.
Objective To retrieve,appraise and summarize the available evidence on management and prevention of implantable venous access port occlusion in adult patients.Methods We searched the BMJ best practice,UpToDate,Cochrane Library,Joanna Briggs Institute Library,Registered Nurses' Association of Ontario,National Guideline Clearinghouse,PubMed,EMbase,CNKI and CBM to collect literatures including guidelines,evidence summary,best practice information sheet,recommended practice,systematic review and consensus.Results Five references including one guideline,one systematic review,two evidence summaries,and one expert consensus were included.A total of eight items of best evidence were summarized with regard to syringe size,flush volume,flush technique and frequency of administration,choose of needleless connectors,management of mechanical occlusion,drug/mineral precipitation,and thrombotic occlusion.Conclusion Healthcare workers should regulate the standard of venous access port flushing and locking and manage catheter occlusion in a timely manner,to avoid adverse incidents like interruptions in treatment,bacteremia,and venous thrombosis.
Traditionally, liver cirrhosis has a bleeding tendency due to the reduction in blood coagulation factors, hyperfibrinolysis, thrombocytopenia, and increased portal hypertension. Some studies show that the patients with live cirrhosis are in a state of hypercoagulability and tend to develop venous thromboembolism, which greatly affects the patients′ prognosis. This article reviews the epidemiological features and risk factors of venous thromboembolism, as well as the significance of prevention of venous thromboembolism in patients with liver cirrhosis, so as to guide clinical practice.
As a way of gene modification,alternative splicing is an important factor of eukaryotic gene expression and regulation.It makes various transcripts from one protein-coding gene,and greatly extends the genetic information.Alternative splicing of pre-messenger RNA plays an important role in tumor cells.By alter-native splicing,some important genes can generate splicing variants different from those in normal cells.The existence of tumor-specific splicing variants leads to the occurrence and progression of tumor.Therefore,explo-ration on the alternative splicing of tumor-associated genes may be of great significance in tumor diagnosis and treatment.
