For decades, mesenchymal stem (MSCs) cells have been used for cardiovascular diseases as regenerative therapy. This review is an attempt to summarize the types of MSCs involved in myocardial infarction (MI) therapy, as well as its possible mechanisms effects, especially the paracrine one in MI focusing on the studies (human and animal) conducted within the last 10 years. Recently, reports showed that MSC therapy could have infarct-limiting effects after MI in both experimental and clinical trials. In this context, various types of MSCs can help cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Furthermore, MSCs could produce paracrine growth factors that increase the survival of nearby cardiomyocytes, as well as increase angiogenesis through recruitment of stem cell from bone marrow or inducing vessel growth from existing capillaries. Recent research suggests that the paracrine effects of MSCs could be mediated by extracellular vesicles including exosomes. Exosomal microRNAs (miRNAs) released by MSCs are promising therapeutic hotspot target for MI. This could be attributed to the role of miRNA in cardiac biology, including cardiac regeneration, stem cell differentiation, apoptosis, neovascularization, cardiac contractility and cardiac remodeling. Furthermore, gene-modified MSCs could be a recent promising therapy for MI to enhance the paracrine effects of MSCs, including better homing and effective cell targeted tissue regeneration. Although MSC therapy has achieved considerable attention and progress, there are critical challenges that remains to be overcome to achieve the most effective successful cell-based therapy in MI.

The current study suggests that intravenous injection of MSCs into rabbits with chemotherapy-induced ovarian damage improved ovarian function. MSCs accomplish this function by direct differentiation into specific cellular phenotypes and by secretion of VEGF, which influence the regeneration of the ovary.

No abstract

Recently, several studies have demonstrated the role of vitamin D receptor (VDR) polymorphisms in the development of systemic lupus erythematosus (SLE). We aimed to evaluate VDR (ApaI, BsmI, and FokI) gene polymorphisms and haplotypes as a risk factors and/or activity markers for SLE, and whether they influence 25-hydroxyvitamin (25(OH) D) level. One hundred and seven SLE patients and 129 controls were enrolled in this study. Disease activity in SLE patients was assessed using Disease Activity Index. Polymorphisms of VDR gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH) D levels were measured using ELISA. We found that ApaI AA genotype, BsmI B allele, Bb, BB genotypes, FokI F allele and FF genotype frequencies of VDR were increased in SLE group. There were significant associations of VDR ApaI AA, BsmI BB, and FokI FF genotypes with lupus nephritis and higher SLE activity scores. Moreover, serum 25(OH) D levels were increased in SLE patients carrying FokI ff genotype compared with patients carrying FF genotype. VDR haplotypes aBF and ABF were associated with SLE risk. The ABF haplotype was associated with higher SLE activity scores and lower serum 25(OH) D concentrations. We observed that the presence of leuko/lymphopenia, renal disorders, higher SLE activity scores and higher anti-dsDNA levels were accompanied by a significant decrease of serum 25(OH)D concentrations. We concluded that The VDR genes polymorphisms, haplotypes, and decreased 25(OH) D levels were associated with risk and more activity scores of SLE.

The matrix metalloproteinases 1 and 3 (MMP1 and MMP3) are thought to be important in destructive joint changes seen in rheumatoid arthritis (RA) and osteoarthritis (OA) diseases. The aim of this study was to analyze whether functional polymorphisms in the promoter region of the MMP1 and MMP3 genes were associated with RA and OA. The MMP1 (-1607 1G/2G) and MMP3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism in 100 patients with (RA), 100 patients with (OA), and 100 controls. Serum MMP1 and MMP3 levels were measured by enzyme-linked immunosorbent assay. The results reported a significant difference between patients with OA and controls regarding allele distributions of MMP1 polymorphism, but not between patients with RA and controls. For MMP3 polymorphism, the 6A/6A genotype was significantly more frequent in patients with RA and OA than in controls. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in the patients with RA and OA than in controls (28%, 30% and 8%, respectively). There were no significant differences in serum MMP1 and MMP3 levels between all studied groups. In conclusion, the MMP1 and MMP3 haplotypes may represent genetic determinants for RA and OA in the Egyptian population. The results suggest that MMP polymorphism genotypes may be more useful in predicting joint damage than measurement of serum concentrations of MMP1 and MMP3. Moreover, MMP1 and MMP3 polymorphisms may predict the activity and severity of these diseases.

No abstract

Obesity, insulin resistance, and hyperandrogenism are considered crucial parameters of polycystic ovary syndrome (PCOS) which might be related to vitamin D metabolism. The aim of this study was to investigate the associations between polymorphisms (TaqI and ApaI) in the vitamin D receptor gene (VDR) and PCOS among Egyptian women. We aimed also to elucidate the impact of these polymorphisms on vitamin D level, hormonal and metabolic parameters of PCOS. One hundred and fifty Egyptian women with PCOS and 150 unrelated controls were enrolled in this study. Polymorphisms of VDR Taq-I T/C (rs731236) and Apa-I A/C (rs7975232) gene were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR–RFLP). Serum 25 hydroxy vitamin D [25(OH) D] levels were measured by high-performance liquid chromatography. PCOS women had significantly lower levels of 25(OH) D compared to healthy women. Our results revealed that Taq-I CC genotype and C allele were associated with increased risk of PCOS, while the Apa-I polymorphism was not. Haplotype Taq-I C/ Apa-I C was associated with a higher PCOS risk more than controls. Moreover, there was a significant decrease of 25(OH) D levels in carriers of haplotype Taq-I C/ Apa-I C (with variant alleles) compared to the non-carriers. Results showed also that there was an obesity- VDR Taq-I genotypes interactions. These results suggested that, VDR Taq-I gene polymorphism is associated with increased risk of PCOS in Egyptian women.

In clinical practice, there is still a need for novel biomarkers, which can reliably rule in or rule out acute coronary syndrome (ACS) immediately on admission. This is of particular interest in patients with unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) in whom diagnostic uncertainty is high. The aim of the present study is to evaluate the potential role of miRNA-499 and miRNA-210 as novel molecular biomarkers for early diagnosis of UA and NSTEMI suspected patients presented at the emergency unit. A total of 110 patients presenting to the intensive care unit (ICU) within 24 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 37 UA, 48 NSTEMI and 25 noncardiac chest pain (NCCP) patients. Immediately at enrollment, blood samples were taken for estimation of serum miRNA-499 and miRNA-210 expression levels by real time PCR. miRNA-499 and miRNA-210 expression levels were significantly increased in UA and NSTEMI patients compared with NCCP patients (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that the area under curve (AUC) of miR-499 for the diagnosis of UA and NSTEMI was 0.98 and 0.97, respectively; while the AUC of miRNA-210 was 0.84 and 0.90, respectively. The important finding of our study was that the AUC of miRNA-499 for the diagnosis of ACS patients with symptoms onset <3 h was 0.89, while the AUC of miRNA-210 was 0.86. Interestingly, combining miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.96, P < 0.001. In conclusion, serum miRNA-499 and miRNA-210 are associated with UA and NSTEMI and with those presenting within 3 h of symptom onset. Both miRNAs might be potentially novel biomarkers for accelerating the diagnosis of ACS patients in emergency unit. V C 2016 IUBMB Life, 68(8):673-682, 2016