The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model.
Various factors may contribute to a hypercoagulable state and acute vascular thrombosis. A prospective study was conducted involving 165 coronary heart disease (CHD) patients from the Cardiology Unit, Hospital Universiti Sains Malaysia. The purpose of this study was to investigate the relationship among factor VIII (FVIII), prothrombin time (PT), activated partial thromboplastin time (APTT), and activated protein C resistance (APC-R) state among CHD patients and to look for potential clinical applications from these laboratory findings. There were 110 cases diagnosed as acute coronary syndrome (ACS), whereas another 55 were stable coronary artery disease (SCAD) patients. PT, APTT, FVIII, and APC-R assays were performed on all subjects. There was a significant difference between the FVIII level and the APTT results (P value < 0.0001). A negative relationship was found between the FVIII level and the APTT from linear regression analysis (R(2) = 10%, P value < 0.0001). For each 1% increase in the FVIII level, the APTT was reduced by 0.013 s (95% confidence interval (CI) between -0.019 and -0.007). Interestingly, none of the SCAD patients had abnormally short APTT. Approximately 68.4% of cases with a positive APC-R assay were found to have a high FVIII level. In conclusion, the APTT test is a potential hemostatic marker for hypercoagulable state including in arterial thrombosis.
Study site: Cardiology unit (outpatient and inpatient), Hospital Universisti Sains Malaysia (HUSM), Kelantan, Malaysia
Oncolytic virotherapy is a therapeutic approach that uses replication-competent viruses to kill cancers. The ability of oncolytic viruses to selectively replicate in cancer cells leads to direct cell lysis and induction of anticancer immune response. Like other anticancer therapies, oncolytic virotherapy has several limitations such as viral delivery to the target, penetration into the tumor mass, and antiviral immune responses. This review provides an insight into the different characteristics of oncolytic viruses (natural and genetically modified) that contribute to effective applications of oncolytic virotherapy in preclinical and clinical trials, and strategies to overcome the limitations. The potential of oncolytic virotherapy combining with other conventional treatments or cancer immunotherapies involving immune checkpoint inhibitors and CAR-T therapy could form part of future multimodality treatment strategies.