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Andrographolide (Andro) has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi) has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS)-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α) decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP) plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death.

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Background: Hepcidin, a peptide hormone composed of 25 amino acids. Hepcidin is synthesized mainly in the liver. Iron deficiency anemia (IDA) is common during pregnancy and is associated with higher maternal morbidity and mortality in Gaza strip. Understanding of hepcidin hormone and its role in iron metabolism could lead to a new sensitive indicator for earlier detection of cases with IDA. Objective: To assess hepcidin status among IDA pregnant women and its relationship with some biochemical variables in Gaza strip. Materials and methods: A case control study comprised 45 IDA pregnant women and 45 apparently healthy pregnant women. Questionnaire interviews were applied among the study population. Serum hepcidin and ferritin were measured by Enzyme-linked immunosorbent assay (ELISA), iron and total iron binding capacity (TIBC) were determined photometrically. Complete blood count (CBC) was also performed. Transferrin and transferrin saturation were calculated. An approval was obtained from Helsinki committee and ministry of health to conduct this study. Overall data were computer analyzed using SPSS (Ver. 18). Results: The mean levels of serum hepcidin, iron, transferrin saturation, and ferritin in cases were significantly lower compared to those of controls (2.6±4 ng/ml, 63.2±25.3 µg/dl, 15.6±8.0% and 8.0±9.7 ng/ml versus 7.5±7.3 ng/ml, 77.7±22.9 µg/dl, 23.5±8.0% and 15.4±14.3 ng/ml respectively with P=0.000). The Pearson correlation test showed that positive significant correlations between hepcidin levels and serum iron, ferritin, and transferrin saturation (P<0.001). On the other hand, negative significant correlations were showed with TIBC and transferrin (P<0.001). Conclusions: Serum hepcidin level has a relationship with anemia among pregnant women. Therefore, monitoring of hepcidin levels can play an important role in management of anemia among pregnant women.

Background: Mesenchymal stem cells (MSCs) are deemed as potential new therapeutic agents for infertility treatment and adipose tissue (AT) becomes a potential MSCs source. To direct MSCs through the differentiation process properly, an environment comparable to the in vivo niche might be indispensable. Objective: This study aims to differentiate human AT-derived MScs (hAD-MScs) into male germ-like cells in vitro using a combination of rabbit Sertoli cells conditioned medium (SCCM), bone morphogenetic protein 4, and retinoic acid. Materials and Methods: MScs were isolated from human ATs of fertile and infertile donors. The verified MScs were differentiated using a 2-step protocol; the first step included 20 ng/ml bone morphogenetic protein 4 treatment. The second step was performed utilizing 1 μM retinoic acid and/or SCCM. The morphological changes and the expression of germ cell (GC)-specific markers: octamer-binding transcription factor- 4; stimulated by retinoic-acid-8, synaptonemal complex protein-3, and protamine-1 were assessed in the treated cells using quantitative polymerase chain reaction. Results: Induction of hAD-MScs resulted in the upregulation of GC-specific genes where SCCM treatment showed the highest expression. The synaptonemal complex protein-3 and protamine-1 gene expression was detected after 19 and 26 days of induction, respectively. PRM1 was detected in hAD-MScs cultured in SCCM earlier than in other treated groups. The treated cells became more elongated-like spindles and formed aggregates. Conclusion: hAD-MScs differentiated to GC lineage exhibited the ability to express GC-specific markers under in vitro conditions, and rabbit’s Sertoli cells can be used for inducing transdifferentiation of hAD-MScs into germ-like cells. Key words: Adipose tissue-derived mesenchymal stem cell, Bone morphogenetic protein 4, Germ-line cells, Retinoic acid, Sertoli cells.