Vitamin D3 reduces the symptoms of ovarian hyperstimulation syndrome in mice and inhibits the release of granulosa cell angiogenic factor through pentraxin 3.

It has been reported that the effective inhibition of vascular endothelial growth factor (VEGF) can prevent the progression of ovarian hyperstimulation syndrome (OHSS). The present study aimed to investigate the mechanism underlying the effect of vitamin D3 (VD3) on OHSS in mouse models and granulosa cells. The effects of VD3 administration (16 and 24 IU) on ovarian permeability were determined using Evans blue. In addition, ovarian pathology, corpus luteum count, inflammatory responses, and hormone and VEGFA levels were assessed using pathological sections and ELISA. Molecular docking predicted that pentraxin 3 (PTX3) could be a potential target of VD3, and therefore, the effects of human chorionic gonadotropin (hCG) and VD3 as well as PTX3 overexpression on the production and secretion of VEGFA in granulosa cells were also investigated using western blotting and immunofluorescence. Twenty-four IU VD3 significantly reversed the increase in ovarian weight and permeability in mice with OHSS. Additionally, VD3 diminished congestion and the number of corpus luteum in the ovaries and reduced the secretion levels of inflammatory factors and those of estrogen and progesterone. Notably, VD3 downregulated VEGFA and CD31 in ovarian tissues, while the expression levels of PTX3 varied among different groups. Furthermore, VD3 restored the hCG-induced enhanced VEGFA and PTX3 expression levels in granulosa cells, whereas PTX3 overexpression abrogated the VD3-mediated inhibition of VEGFA production and secretion. The present study demonstrated that VD3 could inhibit the release of VEGFA through PTX3, thus supporting the beneficial effects of VD3 administration on ameliorating OHSS symptoms.

Novel albumin-binding multifunctional probe for synergistic enhancement of FL/MR dual-modal imaging and photothermal therapy.

The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility. Albumin can protect GIAs from the recognition and clearance by the mononuclear phagocytic system (MPS). High plasma concentration and long half-life allow GIAs to accumulate continuously in the tumor area through EPR effect and specific uptake of tumor. Because of the prolonged rotational correlation time (τR) of Gd chelates, GIAs exhibited superior MR contrast performance over GIs with more than 3 times enhancement of longitudinal relaxation efficiency (r1). The fluorescence quantum yield and photothermal conversion efficiency of GIAs was also significantly improved due to the constrained geometry, disrupted aggregation and enhanced photothermal stability. This simple and feasible strategy successfully resulted in a synergistic effect for FL/MR dual-modal imaging and photothermal therapy, which can cast a new light for the clinical translation of multifunctional probes.

Retrospective Cohort Study of Shear-Wave Elastography and Computed Tomography Enterography in Crohn's Disease.

Distinguishing between inflammatory and fibrotic lesions drastically influences treatment decision-making regarding Crohn's disease. However, it is challenging to distinguish these two phenotypes before surgery. This study investigates the diagnostic yield of shear-wave elastography and computed tomography enterography to distinguish intestinal phenotypes in Crohn's disease. Thirty-seven patients (mean age, 29.51 ± 11.52; 31 men) were evaluated with average value of shear-wave elastography (Emean) and computed tomography enterography (CTE) scores. The results demonstrated that a positive correlation between the Emean and fibrosis (Spearman's r = 0.653, p = 0.000). The cut-off value for fibrotic lesions was 21.30 KPa (AUC: 0.877, sensitivity: 88.90%, specificity: 89.50%, 95% CI:0.755~0.999, p = 0.000). The CTE score showed a positive correlation with inflammation (Spearman's r = 0.479, p = 0.003), and a 4.5-point grading system was the optimal cut-off value for inflammatory lesions (AUC: 0.766, sensitivity: 73.70%, specificity: 77.80%, 95% CI: 0.596~0.936, p = 0.006). Combining these two metrics improved the diagnostic performance and specificity (AUC: 0.918, specificity: 94.70%, 95% CI: 0.806~1.000, p = 0.000). In conclusion, shear-wave elastography can be used to help detect fibrotic lesions and the computed tomography enterography score emerged as a feasible predictor of inflammatory lesions. The combination of these two imaging techniques is proposed to distinguish intestinal predominant phenotypes.

Case Report: Treatment of Hypertrophic Cardiomyopathy With Stereotactic Body Radiotherapy.

Patients with hypertrophic cardiomyopathy (HCM), which is characterized by left ventricular hypertrophy, is usually treated with medications such as calcium channel blockers or beta-blockers and invasive treatments such as transcatheter alcohol septal ablation, percutaneous radiofrequency ablation, or heart transplantation. However, non-invasive methods have not been employed for the management of patients with HCM. A 71-year-old male who presented with occasional chest pain for approximately 2 months and had been diagnosed with HCM since he was 39 years old due to occasional fainting was treated with a novel method for HCM using stereotactic body radiotherapy (SBRT). The administration of 25 Gy of radiation as one fraction led to an improvement in his quality of life. No toxicity occurred during or immediately after the treatment. Our observations suggest that SBRT may be a reasonable treatment approach for patients with HCM who are not suitable for surgery.

Analysis of aDR5scFv with Specific Identification and Function.

Death receptor 5 (DR5) can selectively induce cell death in a wide variety of tumor cells. However, at least certain versions of the recombinant soluble TRAIL (sTRAIL) or anti-DR5 monoclonal antibody (mAb) are also shown to cause apoptosis in normal cells (especially in hepatocytes), hampering its clinical use for cancer therapy. Recently, the development of small recombinant antibody fragments as high-affinity therapeutic reagents with reduced immunogenicity has come under the spotlight. A popular format of engineered recombinant antibody fragment is the single-chain fixed-variable (scFv) molecule, in which the VH and VL regions of the parental antibody are joined by a polypeptide linker. The scFv fragment retains the target specificity and antigen binding affinity of the intact antibody, whereas it can be genetically designed and produced in large quantities by ectopically expressing both VH and VL regions from a single cDNA in cells. In this study, an aDR5scFv was constructed and expressed, and it was conformed so that it could recognize and bind eDR5 specifically. The therapeutic effects on human lung adenocarcinoma cells lines 973 in vitro and in vivo were detected by MTT assay, flow cytometry, hematoxylin and eosin staining, and TUNEL assay. aDR5scFv was able to induce 973 cell apoptosis in an in vitro system. The protein expressions of caspase-3, Bax, and cytochrome c were raised, and aDR5scFv also inhibited tumor growth in mice with its effect as well as with radiotherapy. It is concluded that aDR5scFv could possibly be considered as a novel therapeutic candidate for the treatment of tumors.

Anti-DR5 mAb inhibits proliferation of human fibroblast-like synovial cells and reduces their cytokine secretion in vitro.

BACKGROUND: We have previously reported that anti-death receptor 5 (DR5) monoclonal antibody (mAb) is therapeutically effective in the treatment of rheumatoid arthritis (RA) in a collagen-induced arthritis rat model. However, the molecular mechanism and the effect of anti-DR5 mAb on proapoptotic genes and cytokine secretion in the human fibroblast-like synovial cells (FLS) requires further clarification. This study may provide new evidence for the application of anti-DR5 mAb as a treatment for RA. METHODS: Human FLS were isolated from patients with RA and were treated with anti-DR5 mAb. An MTT assay and flow cytometry were used to detect the induction of apoptosis in vitro. Cytokine secretion by the FLS was detected using the enzyme-linked immunosorbent assay. The mRNA expression was assessed by reverse transcription polymerase chain reaction, and the protein expression was analyzed by Western blot. The apoptotic pathway was investigated further using a caspase inhibition assay. RESULTS: Anti-DR5 mAb-induced apoptosis in human RA FLS in vitro. The protein expressions of caspase-8, -3, and -9 were decreased in human anti-DR5 mAb-treated FLS in a dose-dependent manner through exposure to a caspase inhibitor, indicating that anti-DR5 mAb induction of apoptosis is through the caspase pathway. Decreased levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected after treatment with anti-DR5 mAb in vitro. CONCLUSION: Anti-DR5 mAb may induce apoptosis in human FLS through the caspase pathway and through decreased secretions of TNF-α and IFN-γ.