Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), isolated from discarded extra-embryonic tissue after birth, are promising candidate source of mesenchymal stem cells (MSCs). Apart from their prominent advantages in abundant supply, painless collection, and faster self-renewal, hUC-MSCs have shown the potencies to differentiate into a variety of cells of three germ layers (such as bone, cartilage, adipose, skeletal muscle, cardiomyocyte, endothelium, hepatocyte-like cluster, islet-like cluster, neuron, astrocyte and oligodendrocyte), to synthesize and secret a set of trophic factors and cytokines, to support the expansion and function of other cells (like hematopoietic stem cells, embryonic stem cells, natural killer cells, islet-like cell clusters, neurons and glial cells), to migrate toward and home to pathological areas, and to be readily transfected with conventional methods. Two excellent previous reviews documenting the characteristics of this cell population with special emphasis on its niche, isolation, surface markers and primitive properties have been published recently. In this review, we will firstly give a brief introduction of this cell population, and subsequently dwell on the findings of differential capacities with emphasis on its therapeutic potentials.

Temozolomide (TMZ) is an alkylating agent currently used as first-line therapy for gliomas treatment due to its DNA-damaging effect. However, drug resistance occurs, preventing multi-cycle use of this chemotherapeutic agent. One of the major mechanisms of cancer drug resistance is enhanced activity of a DNA repair enzyme, O6-methylguanine-DNA-methyltransferase (MGMT), which counteracts chemotherapy-induced DNA alkylation and is a key component of chemoresistance. MGMT repairs TMZ-induced DNA lesions, O6-meG, by transferring the alkyl group from guanine to a cysteine residue. This review provides an overview of recent advances in the field, with particular emphasis on the inhibitors of MGMT and underlying mechanisms. Literature search was performed through PubMed and all relevant articles were reviewed, with particular attention to MGMT, its role in TMZ-resistant gliomas, effects of MGMT inhibitors and the underlying mechanisms. Several strategies are currently being pursued to improve the therapeutic efficacy of TMZ via inhibition of MGMT to reduce chemoresistance and improve overall survival. MGMT may be a promising target for the treatment of TMZ-resistant gliomas.

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ObjectiveTo investigate whether elevated plasma trimethylamine N-oxide (TMAO) levels are associated with initial stroke severity and infarct volume.MethodsThis cross-sectional study included 377 patients with acute ischemic stroke and 50 healthy controls. Plasma TMAO levels were assessed at admission. Stroke infarct size and clinical stroke severity were measured with diffusion-weighted imaging and the NIH Stroke Scale (NIHSS). Mild stroke was defined as an NIHSS score <6.ResultsPlasma TMAO levels were higher in patients with ischemic stroke than in healthy controls (median 5.1 vs 3.0 μmol/L; p < 0.001). Every 1–µmol/L increase in TMAO was associated with a 1.13-point increase in NIHSS score (95% confidence interval [CI] 1.04–1.29; p < 0.001) and 1.69-mL increase in infarct volume (95% CI 1.41–2.03; p < 0.001) after adjustment for vascular risk factors. At admission, 159 patients (42.2%) had experienced a mild stroke, and their plasma TMAO levels were lower compared to those with moderate to severe stroke (median 3.6 vs 6.5 µmol/L; p < 0.001). The area under the receiver operating characteristics curve of plasma TMAO level in predicting moderate to severe stroke was 0.794 (95% CI 0.748–0.839; p < 0.001), and the optimal cutoff value was 4.95 μmol/L. The sensitivity and specificity of TMAO levels ≥4.95 μmol/L for moderate to severe stroke were 70.2% and 79.9%, respectively.ConclusionsPatients with ischemic stroke had higher plasma TMAO levels compared to healthy controls. Higher plasma TMAO level at admission is an independent predictor of stroke severity and infarct volume in patients with acute ischemia.