Human pluripotent stem cells have the potential assist in the identification of genes involved in mammalian development. The human placenta is considered a repository of stem cells, termed placenta-derived multipotent cells (PDMCs), which are able to differentiate into cells with an osteoblastic phenotype. This plasticity of PDMCs maybe applied clinically to the understanding of osteogenesis and osteoporosis. In the presentstudy, osteoblasts were generated by culturing PDMCs in osteogenic medium. Reverse transcription quantitative polymerase chain reactionand the degree of osteoblast calcification were used to evaluate the efficacy of osteogenesis. The results suggestedthat the expression of mothers against decapentaplegic homolog 3 (SMAD3) increased in the initial stages of osteogenic differentiation but decreased in the later stages. However, osteogenesis was inhibitedwhen the PDMCs overexpressed SMAD3 throughout the differentiation period. In addition, the rate of osteogenic differentiation was decreased when SMAD3 signaling was impaired. In conclusion, SMAD3 serves an important role in osteoblast differentiation and bone formation in a time-dependent manner. The data from the present study indicate that arapid increase in SMAD3 expression is crucial for osteogenesis and suggest a role for PDMCs in the treatment of patients with osteoporosis.

Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.

DESCRIPTIONThe patient is a 16-year-old girl who visited the clinic and presented with a 3-month history of right foot pain. She described the pain as constant and dull, and exacerbated with walking. No traumatic history was noted. Physical examination revealed evident swelling and tenderness near the second metatarsophalangeal (MTP) joint. Radiograph of the right foot revealed flattening of the second metatarsal head with subchondral sclerosis and fragmentation within the joint (figure 1). In addition, MRI demonstrated hyperintense signals on T2-weighted images ( figure 2A,B). Based on clinical and radiological information, Freiberg's infraction was diagnosed and the patient was treated conservatively with rest and activity modification. After 2 months of follow-up, she was walking pain-free.Freiberg's infraction is a rare disease characterised by osteonecrosis of the metatarsal head primarily affecting the second metatarsal.1 With its multifactorial aetiology, the condition predominantly occurs in teenagers with a 5 : 1 female predilection. 2Patients often present with pain and swelling around the MTP joint.1 The radiographic appearance is typical with flattening of the second metatarsal head, increased sclerosis and loose body formation within the joint. MRI is useful in its diagnosis, as T2-weighted images often show increased signal intensity in the metatarsal head.3 Since most cases are self-limited, conservative therapy in the form of rest, crutches or casting may be adequate. Surgery is rarely indicated and is reserved for patients who fail conservative management; it can range from metatarsal neck osteotomy and joint debridement to resection of the metatarsal head.

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