The protective effect of hydroalcoholic extract of Ephedra pachyclada leaves on ovarian damage induced by cyclophosphamide in rat: An experimental study.

Background: Cyclophosphamide (CP) is an anticancer drug that acts as an alkylation agent after metabolism in the liver. CP has toxic effects on the body's cells, especially the reproductive system's function, and causes infertility. Moreover, medicinal plants have few side effects and are psychologically acceptable to patients. Objective: This study aimed to investigate the impact of Ephedra pachyclada hydroalcoholic extract (EPHE) on ovarian tissue and hypothalamic-pituitary-gonadal axis in rats treated with CP. Materials and Methods: In this experimental study, 48 adult female Wistar rats (180-200 gr, 9-10 wk) were randomly assigned to 6 experimental groups (n = 8/each): (a) control; (b) sham; (c) CP; (d) CP+250 mg/kg EPHE; (e) CP+500 mg/kg EPHE; (f) CP+1000 mg/kg EPHE. On the 29th day of the experiment, serum was collected; serum concentration of the luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and antioxidant activity were measured. The number of ovarian follicles were also counted. Results: In the CP groups, serum concentrations of follicle-stimulating hormone and luteinizing hormone significantly increased, and estrogen and progesterone significantly decreased (p ≤ 0.05). EPHE significantly compensated for the complications caused by CP and 1000 mg/kg had the greatest effect. Antioxidant reduction by CP was significantly enhanced by EPHE, especially at higher doses (p ≤ 0.05). The number of primordial, primary, secondary, and Graafian follicles showed a significant decrease in CP groups and EPHE groups showed a significant increase compared to the CP. EPHE showed that the concentration of 1000 mg/kg was more effective than other doses (p ≤ 0.05). Conclusion: In addition to proving the effect of EPHE on the hypothalamic-pituitary-gonadal axis, our investigation showed antioxidant properties, which can be an effective factor in CP-treated rats.

The matrix microenvironment influences but does not dominate tissue-specific stem cell lineage differentiation.

Mesenchymal stem cells (MSCs) play a pivotal role in tissue engineering and regenerative medicine, with their clinical application often hindered by cell senescence during ex vivo expansion. Recent studies suggest that MSC-deposited decellularized extracellular matrix (dECM) offers a conducive microenvironment that fosters cell proliferation and accentuates stem cell differentiation. However, the ability of this matrix environment to govern lineage differentiation of tissue-specific stem cells remains ambiguous. This research employs human adipose-derived MSCs (ADSCs) and synovium-derived MSCs (SDSCs) as models for adipogenesis and chondrogenesis differentiation pathways, respectively. Genetically modified dECM (GMdECM), produced by SV40LT-transduced immortalized cells, was studied for its influence on cell differentiation. Both types of immortalized cells displayed a reduction in chondrogenic ability but an enhancement in adipogenic potential. ADSCs grown on ADSC-deposited dECM showed stable chondrogenic potential but increased adipogenic capacity; conversely, SDSCs expanded on SDSC-generated dECM displayed elevated chondrogenic capacity and diminished adipogenic potential. This cell-dependent response was confirmed through GMdECM expansion, with SDSCs showing enhanced chondrogenesis. However, ADSCs did not exhibit improved chondrogenic potential on GMdECM, suggesting that the matrix microenvironment does not dictate the final differentiation path of tissue-specific stem cells. Potential molecular mechanisms, such as elevated basement membrane protein expression in GMdECMs and dynamic TWIST1 expression during expansion and chondrogenic induction, may underpin the strong chondrogenic differentiation of GMdECM-expanded SDSCs.

The effect of leaf hydroalcoholic extract of Ephedra pachyclada infertility in male rats treated with cyclophosphamide: An experimental study.

Background: Cyclophosphamide (CP) has clinical applications in treating diverse malignancies and autoimmune disorders; at the same time, it also has harmful effects on the body tissues, particularly the genitals. The most significant side effects of CP are changing the reproductive system's function and infertility. Objective: This study determines the Ephedra hydroalcoholic extract (EP) role on testicular tissue and the pituitary-gonadal axis in CP-treated male rats. Materials and Methods: In this experimental study, 48 adult Wistar rats were separated into 6 groups (n = 8/each): control, sham, CP recipients, and CP recipients with gavage-fed EP (250, 500, and 1000 mg/kg). On the 29th day, the blood of the weighed animals' was drawn from their heart, and serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone were measured. After preparing testicular tissue segments, cells were counted. Results: While CP decreased follicle-stimulating hormone, luteinizing hormone, and testosterone levels (p < 0.05), the use of EP changed them and even reached the control. Serum gonadotropin-releasing hormone increased significantly in all EP groups compared to the control and CP groups. Compared to the control, a significant decrease in total antioxidant capacity and plasma glutathione peroxidase was observed in the CP groups. EP (all doses) significantly increased their concentration compared to the CP group (p < 0.05); significant reduction in serum total oxidant status and malondialdehyde in CP groups changed by EP (p < 0.05). Although CP's role on spermatogonia counts (57.5 ± 5.2 in CP, 67.1 ± 6.0 in control), higher doses of EP had no significant effect on this but did affect spermatocyte and spermatid cells count. Conclusion: Due to its antioxidant characteristics, EP mitigated the effects of CP on the investigated parameters in rats.

Tissue-Engineered Core-Shell Silk-Fibroin/Poly-l-Lactic Acid Nerve Guidance Conduit Containing Encapsulated Exosomes of Human Endometrial Stem Cells Promotes Peripheral Nerve Regeneration.

Nerve guide conduits (NGCs) have been shown to be less efficient than nerve autografts in peripheral nerve regeneration. To address this issue, we developed for the first time a novel tissue-engineered nerve guide conduit structure encapsulated with human endometrial stem cell (EnSC) derived exosomes, which promoted nerve regeneration in rat sciatic nerve defects. In this study, we initially indicated the long-term efficacy and safety impacts of newly designed double layered SF/PLLA nerve guide conduits. Then the regeneration effects of SF/PLLA nerve guide conduits containing exosomes derived from human EnSCs were evaluated in rat sciatic nerve defects. The human EnSC derived exosomes were isolated from the supernatant of human EnSC cultures and characterized. Subsequently, the human EnSC derived exosomes were encapsulated in constructed NGCs by fibrin gel. For in vivo studies, entire 10 mm peripheral nerve defects were generated in rat sciatic nerves and restored with NGC encapsulated with human EnSC derived exosomes (Exo-NGC group), nerve guide conduits, and autografts. The efficiency of the NGCs encapsulated with human EnSCs derived exosomes in assisting peripheral nerve regeneration was investigated and compared with other groups. The in vivo results demonstrated that encapsulated human EnSC derived exosomes in NGC (Exo-NGC) significantly benefitted nerve regeneration based on motor function, sensory reaction, and electrophysiological results. Furthermore, immunohistochemistry with histopathology results showed the formation of regenerated nerve fibers, along with blood vessels that newly were developed, as a result of the exosome functions in the Exo-NGC group. These outcomes illustrated that the newly designed core-shell SF/PLLA nerve guide conduit encapsulated with human EnSC derived exosomes enhanced the regeneration process of axons and improved the functional recovery of rat sciatic nerve defects. So, encapsulated human EnSC-derived exosomes in a core-shell SF/PLLA nerve guide conduit are a potential therapeutic cell-free treatment for peripheral nerve defects.

Matrix from urine stem cells boosts tissue-specific stem cell mediated functional cartilage reconstruction.

Articular cartilage has a limited capacity to self-heal once damaged. Tissue-specific stem cells are a solution for cartilage regeneration; however, ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration. Our previous report demonstrated that decellularized extracellular matrix (dECM) deposited by human synovium-derived stem cells (SDSCs), adipose-derived stem cells (ADSCs), urine-derived stem cells (UDSCs), or dermal fibroblasts (DFs) provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential, particularly for dECM deposited by UDSCs. To make the cell-derived dECM (C-dECM) approach applicable clinically, in this study, we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells (IPFSCs), an easily accessible alternative for SDSCs, by the abovementioned C-dECMs, in vivo application for functional cartilage repair in a rabbit osteochondral defect model, and potential cellular and molecular mechanisms underlying this rejuvenation. We found that C-dECM rejuvenation promoted rabbit IPFSCs' cartilage engineering and functional regeneration in both ex vivo and in vivo models, particularly for the dECM deposited by UDSCs, which was further confirmed by proteomics data. RNA-Seq analysis indicated that both mesenchymal-epithelial transition (MET) and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs' chondrogenic capacity, which needs further investigation.

Anti-Cancer and Anti-Bacterial Effects of Terfezia boudieri-Derived Silver Nanoparticles.

BACKGROUND: The use of nanoparticles has markedly increased in biomedical sciences. The silver nanoparticles (AgNPs) have been investigated for their applicability to deliver chemotherapeutic/antibacterial agents to treat cancer or infections disease. However, the existing chemical and physical methods of synthesizing AgNPs are considered inefficient, expensive and toxic. METHODS: Natural products have emerged as viable candidates for nanoparticle production, including the use of Terfezia boudieri (T. boudieri), a member of the edible truffle family. Accordingly, our goal was to synthesize AgNPs using an aqueous extract of T. boudieri (green synthesized AgNPs). Since certain infectious agents are linked to cancer, we investigated their potential as anti-cancer and antibacterial agents. RESULTS: The synthesis of AgNPs was confirmed by the presence of an absorption peak at 450nm by spectroscopy. The physico-chemical properties of green synthesized AgNPs were analyzed by UV-Vis, FT-IR, XRD, SEM, and TEM. In addition, their potential to inhibit cancer cell (proliferation and the growth of infectious bacteria were investigated. CONCLUSION: The size of nanoparticles ranged between 20-30nm. They exerted significant cytotoxicity and bactericidal effects in a concentration and time-dependent manner compared to T. boudieri extract alone. Interestingly, the synthesis of smaller AgNPs was correlated with longer synthesis time and enhanced cytotoxic and bactericidal properties.