The relationship of sperm DNA integrity with serum vitamin levels (folate and cobalamin) and food consumption in infertile men.

OBJECTIVE: The aim of this study was to investigate the relationships of serum folate (vitamin B9), cobalamin (vitamin B12) levels and diet with semen parameters (semen standard parameters [SSP] and DNA fragmentation index [DFI]) in infertile men. METHODS: Sperm samples were assessed for SSP and DFI (using the sperm chromatin dispersion test). Serum vitamin concentrations were measured with an immuno-electrochemiluminescence assay, and men completed a semi-quantitative food frequency questionnaire (FFQ). RESULTS: Serum folate levels were positively correlated with sperm progressive motility and DFI. A comparison of SSP between two groups of patients according to serum folate concentration (B9 <4.840 ng/mL and B9 ≥4.840 ng/mL) showed significantly higher sperm concentration and sperm progressive motility in the latter group. However, there was no difference between these groups regarding DFI. Interestingly, serum folate levels were significantly higher in patients with a high DFI (using the cut-offs of 30% or 18%). FFQ data showed that the consumption of fruits and egg yolk correlated positively with sperm concentration and sperm motility, respectively. CONCLUSION: Serum folate levels showed significant associations with sperm concentration and sperm progressive motility. However, the positive association of serum folate with DFI raises the need for careful prescription of folate supplements.

Etoposide-based therapy for severe forms of COVID-19.

The new coronavirus infection COVID-19 has quickly become a global health emergency. Mortality is principally due to severe Acute Respiratory Distress Syndrome (ARDS) which relays only on supportive treatment. Numerous pathological, clinical and laboratory findings rise the similarity between moderate to severe COVID-19 and haemophagocytic lymphohistiocytosis (HLH). Etoposide-based protocol including dexametasone is the standard of care for secondary HLH. The protocol has been successfully used in HLHs that are secondary to EBV and H1N1 infections by inducing complete response and prolonged survival. These observations prompt to consider this cytotoxic therapy in HLH associated to moderately severe to severe forms of COVID-19.

Buccal micronucleus cytome biomarkers in Algerian couples with idiopathic infertility.

The buccal micronucleus cytome (BMCyt) assay is a useful and a minimally invasive cytogenetic method for measuring genomic damage. The aim of the present study is to evaluate the extent of chromosomal damage in couples with idiopathic infertility using a BMCyt. This study included 54 patients (27 couples) with idiopathic infertility and 30 fertile subjects (15 couples). When evaluated by individual (each subject from the couple is considered separately), the frequencies of micronucleated cells (MNC), total micronuclei (TMN), nuclear buds (NBUD), and binucleated cells (BN) were significantly higher in the infertile individuals than in the fertile ones (p = 0.009, p = 0.009, p = 0.003 and p < 0.0001, respectively). Among the cells reflecting cell death events, condensed chromatin (CC), karyorrhectic (KHC) and pyknotic (PYK) cells were significantly higher in the infertile individuals (p = 0.0001, p = 0.003, p = 0.001, respectively). Identical results were obtained when data were analysed by couple (female + male). The frequencies of MNC, TMN, NBUD, and BN cells were significantly higher in the infertile couples (p = 0.019, p = 0.021, p = 0.013, and p < 0.0001, respectively). Likewise, CC, KHC and PYK cells were significantly higher in the infertile couples (p = 0.002, p = 0.034, p = 0.008, respectively). BN cells showed the most pronounced difference between the fertile and infertile groups. The basal (BAS) and karyolitic (KYL) cells did not show a significant difference. In conclusion, this study showed that, in comparison to controls, couples with idiopathic infertility had significantly higher frequencies of DNA damage biomarkers (MN and NBUD), biomarkers of cytokinesis-failure or arrest (BN cells) and cell death biomarkers (CC, KHC and PYK cells). These results suggest a possible role of chromosomal damage in idiopathic infertility that may be due to an imbalance between DNA damage rates and DNA repair mechanisms.

Antitumor effect of Deoxypodophyllotoxin on human breast cancer xenograft transplanted in BALB/c nude mice model.

Recently, biologically active compounds isolated from plants used in herbal medicine have been the center of interest. Deoxypodophyllotoxin (DPT), structurally closely related to the lignan podophyllotoxin, was found to be a potent antitumor and antiproliferative agent, in several tumor cells, in vitro. However, DPT has not been used clinically yet because of the lack of in vivo studies. This study is the first report demonstrating the antitumor effect of DPT on MDA-MB-231 human breast cancer xenografts in nude mice. DPT, significantly, inhibited the growth of MDA-MB-231 xenograft in BALB/c nude mice. The T/C value (the value of the relative tumor volume of treatment group compared to the control group) of groups treated with 5, 10, and 20 mg/kg of intravenous DPT-HP-ß-CD was 42.87%, 34.04% and 9.63%, respectively, suggesting the positive antitumor activity of DPT. In addition, the antitumor effect of DPT-HP-ß-CD (20 mg/kg) in human breast cancer MDA-MB-231 xenograft was more effective than etoposide (VP-16) (20 mg/kg) and docetaxel (20 mg/kg). These findings suggest that this drug is a promising chemotherapy candidate against human breast carcinoma.

ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer.

Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphism is associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphism could represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy.

Sperm DNA fragmentation and standard semen parameters in algerian infertile male partners.

PURPOSE: To date, standard semen parameters have been the only parameters investigated in sperm samples of infertile men in Algeria. We investigated, for the first time, semen parameters according to sperm DNA fragmentation (SDF) in these subjects. MATERIALS AND METHODS: SDF was determined by a validated sperm chromatin dispersion test in 26 infertile men. Patients were split into two groups according to the SDF level estimated by the DNA fragmentation index (DFI): the low fragmentation group (LFG; LFG with DFI ≤18%) and high fragmentation group (HFG; HFG with DFI >18%). The standard semen parameters were measured in both groups. RESULTS: We found that semen concentration and motility were negatively correlated with DFI (r=-0.65, r=-0.45, respectively; p<0.05), while morphology and semen volume were not correlated with it (r=0.24, r=-0.18, respectively; p>0.05). Comparison of the sperm concentration revealed that it was significantly higher in LFG than in HFG (37.57%±13.16% vs. 7.32%±3.59%, respectively; p<0.05), whereas no significant difference was observed regarding sperm motility and morphology. CONCLUSIONS: Our findings suggest that SDF correlates well with both sperm motility and concentration but not with morphology. Thus, we conclude that SDF evaluation provides additional information regarding sperm quality, and should be used as a complementary test for assessing semen characteristics in infertile males.

CD99 expressed on human mobilized peripheral blood CD34+ cells is involved in transendothelial migration.

Hematopoietic progenitor cell trafficking is an important phenomenon throughout life. It is thought to occur in sequential steps, similar to what has been described for mature leukocytes. Molecular actors have been identified for each step of leukocyte migration; recently, CD99 was shown to play a part during transendothelial migration. We explored the expression and role of CD99 on human hematopoietic progenitors. We demonstrate that (1) CD34+ cells express CD99, albeit with various intensities; (2) subsets of CD34+ cells with high or low levels of CD99 expression produce different numbers of erythroid, natural killer (NK), or dendritic cells in the in vitro differentiation assays; (3) the level of CD99 expression is related to the ability to differentiate toward B cells; (4) CD34+ cells that migrate through an endothelial monolayer in response to SDF-1alpha and SCF display the highest level of CD99 expression; (5) binding of a neutralizing antibody to CD99 partially inhibits transendothelial migration of CD34+ progenitors in an in vitro assay; and (6) binding of a neutralizing antibody to CD99 reduces homing of CD34+ progenitors xenotransplanted in NOD-SCID mice. We conclude that expression of CD99 on human CD34+ progenitors has functional significance and that CD99 may be involved in transendothelial migration of progenitors.