Combined use of platelet-rich plasma and adipose tissue-derived mesenchymal stem cells shows a synergistic effect in experimental spinal cord injury

Spinal cord injury (SCI) as a crippling disability causes tissue degeneration via neuron loss and fiber disruption. Some researchers have tried to reverse or minimize these changes. Platelet-rich plasma (PRP) is a biological product derived from peripheral blood containing a variety of growth factors. PRP has been extensively used in regenerative medicine. On the other hand, via secreting neuroprotective growth factors, mesenchymal stem cells (MSCs) have shown a promising potential in repairing central nervous system deficits. This study investigated the therapeutic effect of the combined use of MSCs and PRP in a rat model of SCI. We used real time-PCR method for evaluation of Bcl-2, Bax and caspase 3 expressions, TUNEL test for apoptotic cell death assessment, and neurofilament NF200 immunohistochemistry for examination of axonal regeneration. The results showed that co-treatment with MSCs and PRP efficiently alleviated the evaluated categories. Significant differences were observed in expression of Bcl-2 and caspase3, but not Bax, apoptotic index and the number of NF200 positive axons (for all P </= 0.01) between co-treatment animals compared with those treated with only MSCs or PRP. In conclusion, this study showed that combination of MSCs and PRP synergistically promotes their therapeutic effects in the SCI

Contribution of estradiol in sex-dependent differences of pentylenetetrazole-induced seizures in rats

In the present study the contribution of estradiol in sex-dependent differences of pentylenetetrazole (PTZ)-induced seizures was investigated in rats. The rats were divided into four groups: 1) sham, 2) ovariectomized (OVX), 3) ovariectomized-estradiol (OVX-Est) and 4) male. The OVX-Est group received estradiol valerate (2 mg/kg; i.m/4 weeks) while, male, sham and OVX groups received vehicle. The animals were injected by PTZ (90 mg/kg). The latencies to minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS), were recorded. Serum 17β-estradiol and testosterone levels were also determined using an Elisa kit. GTCS latency in OVX rats was higher than in sham-operated animals (P < 0.05). MCS and GTCS latency in the male group was significantly higher than in the sham, OVX and OVX-Est groups (P < 0.001 and P < 0.01). There was no significant difference in MCS or GTCS latencies among OVX-Est, sham and OVX groups. Serum 17β-estradiol level in the OVX group was significantly lower than in the sham (P < 0.01) and in the OVX-Est group it was higher than in the sham, OVX and male groups (P < 0.01 and P < 0.001). Serum testosterone level in the male group was significantly higher than in all the other three groups (P < 0.001). It seems that testosterone probably has a more efficient role than estradiol in the gender dependent difference in seizure caused by PTZ in rats

Short-term regular moderate exercise improved male hypothalamic-pituitary-gonadal axis function via the reduction of hypothalamic neurokinin b expression in adult rats

Introduction: In the arcuate nucleus, kisspeptin, neurokinin-B and pro-dynorphin (KNDy) neurons control the function of gonadotropin-releasing hormone (GnRH) neurons. Early investigations indicated that exercise with various intensities affects luteinizing hormone (LH) and testosterone (T) in different ways. Meanwhile the molecular mechanisms underlying its function not yet been fully understood. Accordingly, the present study evaluated the role of alterations in the levels of KNDy mRNA upstream of GnRH neurons in conveying the effects of various short-term exercise intensities on the male hypothermic-pituitary-gonadal (HPG) axis. Methods: Twenty-one adult Wistar rats were randomly divided into 3 groups: control, one-month regular moderate exercise (ME) and one-month regular intensive exercise (IE). In ME (22m/min) and IE (35m/min) groups, the rats were treated 5 days a week for 60min each day. Finally, we assessed serum levels of LH and T using the ELIZA technique and KNDy and Gnrh mRNA expression by the real-time PCR method. Results: The results revealed that in ME group the expression of Nkb was reduced and the expression of Gnrh mRNA and the LH and T serum levels were increased. However, intensive exercise did not change the serum levels of LH and T or the relative expression of kiss1, Nkb, Pdyn and Gnrh genes. Conclusion: The results suggested that monthly moderate exercise improved male reproductive axis function, while intensive exercise did not have an adverse effect on the reproductive axis. These various effects on the male HPG axis may be propagated by the change in hypothalamic Nkb gene expression. © 2021, Iranian Society of Physiology and Pharmacology. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Study of the mechanisms of crocetin-induced differentiation and apoptosis in human acute promyelocytic leukemia cells

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti-APL drugs, all-trans retinoic acid (ATRA, 10 µM) and As2O 3 (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl-DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes CASP3, CASP9, and BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As 2O 3 (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor-α (PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 (HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment. © 2018 Wiley Periodicals, Inc