Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application.

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although the current tumor treatment methods have therapeutic effect to a certain extent, they still have some shortcomings such as poor water solubility, short half-life, local and systemic toxicity. Therefore, how to deliver therapeutic agent so as to realize safe and effective anti-tumor therapy become a problem urgently to be solved in this field. As a medium of information exchange and material transport between cells, exosomes are considered to be a promising drug delivery carrier due to their nano-size, good biocompatibility, natural targeting, and easy modification. In this review, we summarize recent advances in the isolation, identification, drug loading, and modification of exosomes as drug carriers for tumor therapy alongside their application in tumor therapy. Basic knowledge of exosomes, such as their biogenesis, sources, and characterization methods, is also introduced herein. In addition, challenges related to the use of exosomes as drug delivery vehicles are discussed, along with future trends. This review provides a scientific basis for the application of exosome delivery systems in oncological therapy.

Excessive aggregation of fine particles may play a crucial role in adolescent spontaneous pneumothorax pathogenesis.

Background: The pathogenesis of primary spontaneous pneumothorax (PSP) is unclear. Fine particles aggregated in the lung can be phagocytosed by alveolar macrophages (AMs) to induce an inflammatory reaction and damage local pulmonary tissue, which could be a mechanism of PSP. This project aimed to explore the pathological association between fine particulate matter and PSP. Methods: Thirty pulmonary bullae tissues were obtained from surgery of PSP patients (B group). The adjacent normal tissues of the lungs were defined as the control S group. Another 30 normal lung tissues with nonpneumothorax disease (NPD) were applied as the control N group. Hematoxylin and eosin (H & E), Wright-Giemsa (W-G), Victoria blue, and immunohistochemical (IHC) staining experiments were performed to measure the levels of fine particulate matter, alveolar macrophages (AMs), pulmonary elastic fibers, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) in the lung tissues. The serum levels of MCP-1 and MMP-9 were prospectively analyzed as well. Results: Histopathological examinations revealed obvious deposition of fine particulate matter and inflammatory reactions (proliferation of AMs) in the B group, compared with those in the S group and the N group. These alterations were significantly associated with PSP. The numbers of AMs and pulmonary elastic fibers, the positive area of the H-score, as well as the concentrations of MCP-1 and MMP-9 in the lungs of the experimental group were obviously raised compared with the controls (P < 0.05). Conclusions: Fine particulate matter aggregation, inflammation (macrophage hyperplasia), and overexpression of MCP-1 and MMP-9 may contribute to the pathogenesis of PSP. The overaccumulation of fine particulate matter may play a crucial part in the occurrence of adolescent and young adult PSP. Trial registration: This project was enrolled on the Chinese Clinical Trial Registry: ChiCTR2100051460.

Establishment of a prediction algorithm for the Honghe minority group based on warfarin maintenance dose.

Background:CYP2C9 and VKORC1 are important factors in warfarin metabolism. The authors explored the effects of these genetic polymorphisms and clinical factors on a warfarin maintenance dose and then established the prediction algorithm for Honghe minorities in China. Materials & methods: Quantitative fluorescence PCR determined the mutation frequency of CYP2C9 and VKORC1-1639 G>A alleles. The authors collected the relevant clinical factors, including age, gender, body surface area (BSA), international normalized ratio value, daily warfarin dose, comorbidity and concomitant prescriptions. Results: The mean values of BSA and international normalized ratio in Honghe minorities were lower than in Han Chinese (p = 0.00). The genotype of CYP2C9*1/*1 and VKORC1-1639 AA was the main allele, the mutationfrequency of VKORC1-1639 AA and the number of male of Honghe minorities were lower than that of Han Chinese (p = 0.013 and p = 0.04). The significances of the effect on actual warfarin dose value were gender, VKORC1 AA mutant, CYP2C9*1/*1, age, hypertension and BSA sequentially. Conclusion: By multiple linear regression analysis with genetic and clinical factors, the authors determined a prediction algorithm for adjusting individual dosing of warfarin in this population. Clinical trial registration number: ChiCTR2100051778.

Blood compatibility evaluations of CaCO3particles.

CaCO3particles, due to their unique properties such as biodegradation, pH-sensitivity, and porous surface, have been widely used as carrier materials for delivering drugs, genes, vaccines, and other bioactive molecules. In these applications, CaCO3particles are often administered intravenously. In this sense, the interaction between CaCO3particles and blood components plays a key role in their delivery efficacy and biosafety, though the hemocompatibility of CaCO3particles has not been evaluated until now. Deficiency in the biosafety information has delayed the clinical use of CaCO3particles in delivery systems. In this work, we investigated the biosafety of CaCO3particles, focusing on theirin vitroandin vivoeffects on key blood components (red blood cells, platelets, etc) and coagulation functions. We foundin vitrothat high concentrations of CaCO3particles can cause the aggregation and hemolysis of red blood cells, with platelet activation and coagulation prolongation.In vivo, we found that intravenously injected CaCO3particles at 50 mg kg-1significantly disturbed the red blood cells, and platelet-related blood routine indexes, but did not induce visible abnormalities in the tissue structures of the key organs. Overall, these effects may be due to the enormous adsorption capability of the porous surface of CaCO3particles. 0.1 mg ml-1of the CaCO3particles exhibit excellent compatibility for their practical applications. These results would be expected to greatly promote thein vivoapplications and clinical use of CaCO3particles in biomedicine.

Role of ultrasound and CT in the early diagnosis and surgical treatment of primary sternal osteomyelitis caused by Salmonella: Case reports.

Primary sternal osteomyelitis (PSO) caused by Salmonella is a rare condition and most commonly associated with sickle cell disease. Only one such case has been previously reported in an infant (age, <1 year) worldwide. The present study reported on two infantile cases of PSO caused by Salmonella in the absence of any hematological diseases. A total of two male infants (age, ≤1 year) were referred to our hospital for fever and rapid breathing accompanied by a chest wall mass involving the lower end of the sternum. Imaging findings on CT and ultrasound, which included sternal segment dislocation, lytic destruction and periosteal elevation, confirmed the diagnosis of PSO. Blood and purulent material cultures confirmed that the causative pathogen was Salmonella. The infants were completely cured by sequential intravenous and oral antibiotics followed by surgical debridement. The infants remained symptom-free and local recurrence of PSO was not detected at follow-up. PSO caused by Salmonella in the absence of any hematological diseases is a rare condition. Unfamiliarity with this disease may lead to a delay in diagnosis and serious complications. The current case report presents two cases of PSO along with a brief overview of the characteristics and management modalities for this condition, and it provides a comprehensive reference for pediatricians regarding this rare disease, particularly in infants.

Effects of ZIF-8 MOFs on structure and function of blood components.

ZIF-8 MOFs, with their large specific surface area and void volume, unique biodegradability and pH sensitivity, and significant loading capacity, have been widely used as carrier materials for bioactive molecules such as drugs, vaccines and genes. In these applications, ZIF-8 MOFs are usually delivered intravenously. Therefore, it is necessary to know the interaction between ZIF-8 MOFs and blood components, which from this sense is a key factor affecting their delivery effectiveness and biosafety. However, until now there has been no report on the evaluation of hemocompatibility of ZIF-8 MOFs. The lack of biosafety information of ZIF-8 MOFs seriously impedes their clinical applications. In this work, we studied the biosafety of two different sizes of ZIF-8 MOFs, mainly focusing on their in vivo and in vitro effects on the key components of blood (red blood cells (RBCs), platelets, etc.) and the coagulation function. It was found that, in vitro, a high concentration of ZIF-8 MOFs could induce RBC aggregation and hemolysis, and prolong the coagulation time. In vivo, intravenous administration of 45 mg kg-1 ZIF-8 MOFs significantly disturbed the RBC and platelet-related blood routine indexes, as well as coagulation function indexes, but it did not cause significant abnormalities in blood coagulation and tissue structures (heart, liver, spleen, lung, and kidney).