mRNA vaccine in gastrointestinal tumors: Immunomodulatory effects and immunotherapy.

Gastrointestinal tumors remain a significant healthcare burden worldwide, necessitating the development of innovative therapeutic strategies. mRNA vaccines have emerged as a promising approach in cancer immunotherapy, harnessing the immune system's potential to recognize and eliminate tumor cells. mRNA vaccines offer several advantages, including their ability to elicit both innate and adaptive immune responses, ease of production, and adaptability to different tumor types. In the context of gastrointestinal tumors, mRNA vaccines hold great potential as a therapeutic strategy. In this review, we will delve into the immunomodulatory mechanisms and immunotherapy strategies of mRNA vaccines in gastrointestinal tumors. Additionally, we will discuss the challenges and ongoing research efforts in optimizing mRNA vaccine development, delivery, and stability. By understanding the potential of mRNA vaccines in addressing the unmet medical need of gastrointestinal tumors, we aim to pave the way for improved treatment strategies and better patient outcomes.

The MRI-based 3D morphologic changes of knee meniscus under knee weight-bearing and early flexion conditions.

There are few studies investigate morphologic changes of knee meniscus in vivo mechanical loading and three-dimensions (3D) deformation and displacement of the whole meniscus between in vivo mechanical loading and unloading conditions are still unclear. To investigate the displacements and 3D morphological changes of the menisci under knee weight-bearing and early flexion conditions in healthy adults using a Magnetic Resonance Imaging (MRI)-compatible loading device (a 3.0 T MR imaging system) combined with a newly developed 3D comparison technique. Fifteen healthy volunteers were recruited in this cross-sectional observational study. Each subject underwent MRIs of their dominant right knee in eight different scanning conditions using a 3.0-T MRI scanner with a custom-made MRI-compatible loading device. The knee meniscus images were 3D reconstructed, and dimensional comparisons were made for each meniscal model with baseline (0°-unloaded model). The morphologic changes of the meniscal-anterior horn (AH), body (BD), and posterior horn (PH) regions were expressed as mean positive and negative deviations. The displacements were further investigated, and the meniscal extrusions of different subregions were measured. The morphologic changing patterns of human meniscus under loading and flexions were presented using 3D chromatic maps. The bilateral menisci were generally shifting laterally and posteriorly in most flexion angles and were changing medially and anteriorly under fully extended knee loading conditions. The mean deviations were more significant with loading at 0° of knee flexion, while the PH region in the lateral side changed further posteriorly with loading in 30° flexion. Most of the differences were not significant in other flexion angles between loading conditions. The extrusion of meniscus's medial body was greater in full extension compared to any other flexing angles. Mechanical loading can significantly deform the menisci in knee extension; however, this effect is limited during knee flexion. Current study can be used as a reference for the evaluations of the integrity in meniscal functions.

Porous polyetheretherketone microcarriers fabricated via hydroxylation together with cell-derived mineralized extracellular matrix coatings promote cell expansion and bone regeneration.

Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer, supporting cell attachment and growth with sufficient cell seeding density. In this study, porous polyetheretherketone (PEEK) microcarriers coated with mineralized extracellular matrix (mECM), known for their chemical, mechanical and biological superiority, were developed for orthopedic applications. Porous PEEK microcarriers were derived from smooth microcarriers using a simple wet-chemistry strategy involving the reduction of carbonyl groups. This treatment simultaneously modified surface topology and chemical composition. Furthermore, the microstructure, protein absorption, cytotoxicity and bioactivity of the obtained porous microcarriers were investigated. The deposition of mECM through repeated recellularization and decellularization on the surface of porous MCs further promoted cell proliferation and osteogenic activity. Additionally, the mECM coated porous microcarriers exhibited excellent bone regeneration in a rat calvarial defect repair model in vivo, suggesting huge potential applications in bone tissue engineering.

Biomimetic polyetheretherketone microcarriers with specific surface topography and self-secreted extracellular matrix for large-scale cell expansion.

Reusable microcarriers with appropriate surface topography, mechanical properties, as well as biological modification through decellularization facilitating repeated cell culture are crucial for tissue engineering applications. Herein, we report the preparation of topological polyetheretherketone (PEEK) microcarriers via gas-driven and solvent exchange method followed by hydrothermal treatment at high temperature and pressure. After hydrothermal treated for 8 h, the resulting topological PEEK microcarriers exhibit walnut-like surface topography and good sphericity as well as uniform size distribution of 350.24 ± 19.44 µm. And the average width between ravine-patterned surface of PEEK microcarriers is 780 ± 290 nm. After repeated steam sterilization by autoclaving for three times, topological PEEK microcarriers show nearly identical results compared with previous ones indicating strong tolerance to high temperature and pressure. This is a unique advantage for large-scale cell expansion and clinical applications. Moreover, PEEK microcarriers with special topography possess higher protein adsorption efficiency. In addition, the reutilization and biofunctionalization with repeated decellularization of topological PEEK microcarriers show highly beneficial for cell adhesion and proliferation. Therefore, our study is of great importance for new generation microcarriers with micro-and nano-scale surface feature for a broad application prospect in tissue engineering.

The Relationship Between Liver Enzymes and Insulin Resistance in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease.

Non-: alcoholic fatty liver disease (NAFLD) is prevalent worldwide, especially in patients with type 2 diabetes. Liver enzymes are the main warning signs of liver injury and insulin resistance (IR) is critical to NAFLD. This study was aimed to investigate the association between liver enzymes and insulin resistance in type 2 diabetes patients with NAFLD. Data from 212 diabetes patients with NAFLD were analyzed, including 118 males and 94 females who received care from 2014 to 2015. The patients were divided into three groups by severity (mild n=87, moderate n=89, severe n=36). All patients underwent standard clinical and laboratory examinations. Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were measured, serum fasting glucose and serum fasting insulin were obtained. IR was assessed using the homeostasis model assessment insulin resistance index (HOMA-IR). Age, sex, and BMI did not significantly differ in patients (p>0.05). Compared with normal levels, elevated ALT and AST were associated with a higher HOMA-IR (p=0.0035, p=0.0096, respectively). HOMA-IR did not significantly differ (p>0.05) between patients with normal and elevated GGT. HOMA-IR increased as the levels of liver enzymes increased, and each enzyme showed a significant association with HOMA-IR (p=0.0166, p<0.0001, and p <0.0001). HOMA-IR differs between normal and elevated ALT and AST. Liver enzymes are associated with HOMA-IR in type 2 diabetes patients with NAFLD. These findings can help evaluate the degree of IR and hepatocellular steatosis in patients and prevent the progression of type 2 diabetes and NAFLD in clinical practice.

[Clinical evaluations of anterior cruciate ligament reconstruction with platelet rich plasma].

Objective: To investigate the clinical outcomes of autologous platelet rich plasma (PRP) for anterior cruciate ligament (ACL) reconstruction. Methods: Between August 2014 and August 2016, 42 patients with ACL ruptures who underwent arthroscopic ACL reconstruction were randomly divided into 2 groups: 21 patients received graft soaked with PRP (trial group) and 21 patients received routine graft in ACL reconstruction (control group). Because 6 patients failed to be followed up, 17 patients of trial group and 19 of control group were enrolled in the study. There was no significant difference in gender, age, body mass index, side, injury reason, disease duration, Kellgren-Lawrence grade, and preoperative visual analogue scale (VAS), Lysholm score, and International Knee Documentation Committee (IKDC) activity scores between 2 groups ( P>0.05). VAS score, Lysholm score, and IKDC activity scores were used to evaluate pain and function at 3 and 12 months postoperatively. Further, second arthroscopy and MRI examination were performed at 12 months postoperatively. Results: The patients in both groups were followed up 3 to 12 months with an average of 9.83 months. The VAS score, Lysholm score, and IKDC activity scores were significantly improved at 3 and 12 months after operation in 2 groups ( P<0.05), and the scores of trial group were significantly better than those of control group at 3 months ( P<0.05), but no significant difference was found between 2 groups at 12 months ( P>0.05). No complications of effusion, infection, and allergy were observed in 2 groups during follow-up. MRI showed good position of ACL grafts and good signal quality of the graft in the majority of the cases. However, mixed hyperintense and presence of synovial fluid at the femoral bone-tendon graft interface were found in 3 patients of trial group and 4 patients of control group, indicating poor remodeling ligamentation. MRI score was 3.53±1.13 in trial group and was 3.21±0.92 in control group, showing no significant difference ( t=0.936, P=0.356). The second arthroscopy examination showed ligament remodeling score was higher in trial group than control group ( t=3.248, P=0.014), but no significant difference was found in synovial coverage score and the incidence of cartilage repair ( t=2.190, P=0.064; χ2=0.090, P=0.764). Conclusion: PRP application in allograft ACL reconstruction can improve knee function and relieve pain after operation, which may also accelerate graft remodeling.