Li-Doped Bioactive Ceramics: Promising Biomaterials for Tissue Engineering and Regenerative Medicine.

Lithium (Li) is a metal with critical therapeutic properties ranging from the treatment of bipolar depression to antibacterial, anticancer, antiviral and pro-regenerative effects. This element can be incorporated into the structure of various biomaterials through the inclusion of Li chloride/carbonate into polymeric matrices or being doped in bioceramics. The biocompatibility and multifunctionality of Li-doped bioceramics present many opportunities for biomedical researchers and clinicians. Li-doped bioceramics (capable of immunomodulation) have been used extensively for bone and tooth regeneration, and they have great potential for cartilage/nerve regeneration, osteochondral repair, and wound healing. The synergistic effect of Li in combination with other anticancer drugs as well as the anticancer properties of Li underline the rationale that bioceramics doped with Li may be impactful in cancer treatments. The role of Li in autophagy may explain its impact in regenerative, antiviral, and anticancer research. The combination of Li-doped bioceramics with polymers can provide new biomaterials with suitable flexibility, especially as bio-ink used in 3D printing for clinical applications of tissue engineering. Such Li-doped biomaterials have significant clinical potential in the foreseeable future.

Genotype-phenotype correlation in Iranian patients with Hb H disease.

Thalassemia is the most common genetic disorder in Iran. Some α-globin genotypes leading to Hb H disease may cause severe anemia and dependence on regular blood transfusions. In this study, 40 patients were analyzed for the molecular basis and the genotype-phenotype correlation of Hb H disease in Iran. α-Globin molecular analysis was performed by polymerase chain reaction (PCR) followed by agarose gel electrophoresis, reverse hybridization test strips or DNA sequencing. The most frequently observed α-globin genotypes were -α(3.7)/- -(MED) in 10 patients (25%), - -(20.5)/α(-5nt)α in six patients (15%) and - -(20.5)/-α(3.7) in four patients (10%). A subset of the identified Hb H genotypes, including - -(MED)/α(CS)α, - -(MED)/α(PolyA2)α and α(CS)α/α(CS)α, was associated with a need for regular or irregular blood transfusions. Our findings provide a basis for predicting phenotype severity by identifying the Hb H genotype and making more selective decisions for prenatal diagnosis.

Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) is a common neuromuscular disorder with progressive paralysis caused by the loss of alpha-motor neurons in the spinal cord. The survival motor neuron (SMN) protein is encoded by 2 genes, SMN1 and SMN2. The most frequent mutation is the biallelic deletion of exon 7 of the SMN1 gene. In SMA, SMN2 cannot compensate for the loss of SMN1, due to the exclusion of exon 7. The aim of our study was to estimate the frequency of the common SMN1 exon 7 deletion in patients referred to our centre for carrier detection and prenatal diagnosis. MATERIALS AND METHODS: We performed the detection of exon 7 deletion of the SMN1 gene for the affected patients and fetuses suspected to have SMA. RESULTS: Of 243 families, 195 were classified as SMA type I, 30 as type II, and 18 as type III according to their family histories. The analysis of exon 7 deletion among living affected children showed that 94% of the patients with SMA type I, 95% with type II families and 100% with type III had homozygous deletions. Of the prenatal diagnoses, 21 (22.8%) of the 92 fetuses were found to be affected and these pregnancies were terminated. CONCLUSIONS: The homozygosity frequency for the deletion of SMN1 exon 7 for all 3 types was (94%), similar to those of Western Europe, China, Japan and Kuwait.

Molecular analysis of the neuronal apoptosis inhibitory protein gene in families with spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy is an autosomal recessive disorder characterized by degeneration of anterior horn cells in the spinal cord leading to progressive muscular weakness and atrophy. The spinal muscular atrophy candidate interval genes including survival motor neuron, the responsible gene in spinal muscular atrophy phenotype expression, neuronal apoptosis inhibitory protein, and P44, potential modifying genes, are located on chromosome 5q13 in two highly homologous copies (telomeric and centromeric) within the spinal muscular atrophy region. METHODS: In this study, the neuronal apoptosis inhibitory protein gene deletion was analyzed in 34 spinal muscular atrophy families, with the consanguinity rate of 65% (22/34), in whom exon 7 of the survival motor neuron-1 gene was already confirmed and was deleted in 79% of the affected individuals. Deletion analysis of exons 5, 6, and 13 of the neuronal apoptosis inhibitory protein-t gene was carried out in our samples. RESULTS: We found 80% neuronal apoptosis inhibitory protein gene deletion in 5q-spinal muscular atrophy patients (91% spinal muscular atrophy-I, 50% spinal muscular atrophy-II and -III), and in 5% (two of forty) of spinal muscular atrophy parents. All the neuronal apoptosis inhibitory protein-deleted samples also lacked the survival motor neuron-1 gene. CONCLUSION: The neuronal apoptosis inhibitory protein gene deletion in spinal muscular atrophy-I was higher than the other spinal muscular atrophy types. The high frequency of neuronal apoptosis inhibitory protein deletion most likely reflects a higher frequency of survival motor neuron-1 deletions compared with survival motor neuron-1 to survival motor neuron-2 gene conversion in this population.