An Ultrasound-Induced Self-Clearance Hydrogel for Male Reversible Contraception.

Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)-induced self-clearance hydrogel capable of real-time monitoring is utilized for in situ injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed. The hydrogel is composed of (i) sodium alginate (SA) conjugated with reactive oxygen species (ROS)-cleavable thioketal (SA-tK), (ii) titanium dioxide (TiO2), which can generate a specific level of ROS after US treatment, and (iii) calcium chloride (CaCl2), which triggers the formation of the hydrogel. For contraception, the above mixture agents are one-time injected into the vas deferens, which can transform from liquid to hydrogel within 160 s, thereby significantly physically blocking the vas deferens and inhibiting movability of sperm. When fertility is needed, a noninvasive remedial ultrasound can make TiO2 generate ROS, which cleaves SA-tK to destroy the network of the hydrogel. Owing to the recanalization, the refertility rate is restored to 100%. Meanwhile, diagnostic ultrasound (D-US, 22 MHz) can monitor the occlusion and recanalization process in real-time. In summary, the proposed hydrogel contraception can be a reliable, safe, and reversible male contraceptive strategy that addresses an unmet need for men to control their fertility.

MicroRNA-545-5p regulates apoptosis, migration and invasion of osteosarcoma by targeting dimethyladenosine transferase 1.

The metastasis of osteosarcoma is a major threat to both adolescents and young adults. Identifying novel targets that may prevent osteosarcoma metastasis is critical in developing advanced clinical therapies for treating this cancer. The present study aimed to explore the mechanism of microRNA (miR)-545-5p in the metastasis of osteosarcoma. The present study identified miR-545-5p as a potential target that was downregulated in both osteosarcoma clinical samples and cell lines, and in the latter, ectopically expressed miR-545-5p caused apoptosis. In addition, miR-545-5p exerted inhibitory effects in osteosarcoma migration and invasion. Overexpression of miR-545-5p induced xenograft growth inhibition in vivo. In addition, miR-545-5p targeted dimethyladenosine transferase 1 (DIMT1), an oncogenic protein that facilitates osteosarcoma proliferation, migration and invasion. Taken together, the results of the present study suggest that miR-545-5p functions as a tumor suppressor in osteosarcoma that promotes apoptosis, while inhibiting migration and invasion by targeting DIMT1. Taken together, the results of the present study suggest two potential novel targets for osteosarcoma treatment and metastasis prevention.

Matrine inhibits the invasive properties of human osteosarcoma cells by downregulating the ERK-NF-κB pathway.

Matrine has been used in anti-inflammatory and anticancer therapies for a long time. However, the antimetastatic effect and molecular mechanism(s) of matrine on osteosarcoma are still unclear. Therefore, the aim of this study was to assess the effects of matrine and related mechanism(s) on osteosarcoma cells. In the study, we found that matrine inhibited the proliferation of osteosarcoma cells in vivo and in vitro and inhibited tumor cell metastasis in vitro at cytotoxic doses. Matrine also decreased the expression of the matrix metalloproteinases-2 and 9, decreased p50 and p65 nuclear translocation, and decreased the phosphorylated level of I-κ-B (IκB)-ß. In addition, matrine reduced the phosphorylated levels of extracellular signal-regulated kinase 1/2 proteins, which regulate the invasion of poorly differentiated cancer cells. Finally, when U2OS cells were grown as xenografts in nude mice, intragastric administration of matrine induced a significant dose-dependent decrease in tumor growth. These results show the anticancer properties of matrine, which include the inhibition of invasion and proliferation of human osteosarcoma cells.

[Surgical treatment of fibrous dysplasia in proximal femur].

OBJECTIVE: To summarize the oncological and functional results of patients with fibrous dysplasia in the proximal femur and explore its clinical effect. METHODS: From Apr. 2007 to Jan. 2009, 15 patients with fibrous dysplasia in proximal femur were treated. There were 9 males and 6 females, ranging in age from 16 to 32 years with an average of 25 years. The course of disease was from 2 months to 16 years with an average of 2 years. Among them, 12 cases were unilateral affection and 3 cases were hibateral affections; 12 cases were one bone and 3 cases more than two bones. The collodiaphyseal angles of 2 cases with coxa adducta was 80 degrees and 100 degrees respectively; and femur lengths were shorter than opposite side (5 cm and 3 cm, respectively). The curettage and allogenous and/or autogenous bone-grafting combined with internal fixation were performed in all patients and valgus osteotomies was performed in 2 case with shepherd's crook deformity. RESULTS: All patients were followed up from 12 to 32 months. Two cases with shepherd's crook deformity, the collodiaphyseal angles recovered after surgery, the relative length of femur was increased 4 cm and 3 cm respectively and they can walk with stick at 4 months after operation. No found recurrence and loosening of internal fixation. Bone graft was absorbed at 3 months and bone healing at 8-12 months after operation. The pain vanished and functions were normal. CONCLUSION: It is an effective method to treat fibrous dysplasia in proximal femur with curettage and bone-grafting combined with internal fixation. Corrective osteotomy and internal fixation with a dynamic hip screw is a good and effective method in treating severe symptomatic shepherd's crook deformity.

[Study of inducing bone marrow-derived mesenchymal stem cells into chondrocytes in vitro].

OBJECTIVE: To explore a method of isolation, culture and chondrogenic phenotype differentiation of mesenchymal stem cell (MSCs) from the bone marrow of rats in vitro and to offer experimental reference for the resources of seeding cells in cartilage tissue engineering. METHODS: MSCs were isolated from bone marrow and purified by density gradient centrifuge and cultured in vitro. The MSC adherence formed and those in passage 3 were chosen to induce into chondrogenic differentiation. After 7, 14, 21 days, immunohistochemical techique was applied to detect the expression of collagen type II. The differentiated cells were implanted on the CPP/PLLA composites. After the cell-scaffold complex was cultured in vitro for one week, the ultrastructure of the scaffold was observed with scanning electron microscopy. RESULTS: The differentiated cells changed from a spindle-like fibroblastic appearance to a polygonal shape, the capability of proliferation was down markedly. Immunohistochemical staining of collagen II were positive for the pass age, especially in the 21st days. Induced MSCs were well adherent to the scaffold composites and the cells were embedded by the cell-matrix. CONCLUSION: Under the induced medium, MSCs can differentiate into chondrogenic phenotype and secrete specificity matrix of cartilage in vitro. MSCs can likely be served as optimal cell source for cartilage tissue engineering.