Abstract:

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counter pulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injections. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (β = −2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.

Abstract

Objective: Clinically, there is an urgent need for small-diameter artificial vascular grafts (SDAVGs) meeting the requirements of rapid endothelialization and thrombotic resistance, and poor vascular remodeling is one of the bottlenecks affecting the clinical transformation of SDAVGs. This study aims to design and fabricate a three-layer biomimetic SDAVG,and utilize single cell RNA-sequencing to explore the mechanism of the vascular remodeling after SDAVG implantation.

Methods: To ensure the safety of the novel three-layer biomimetic SDAVGs in vivo, we evaluated their biocompatibility and hemocompatibility firstly. Then, a porcine carotid artery replacement model was established to analyze the biological performance of the three-layer biomimetic small-diameter artificial vascular graft, and histopathological analysis of tissue sections of vascular grafts was performed by HE and immunohistochemical staining. Additionally, single cell transcriptome sequencing was used to investigate the cell composition and changes after blood vessel implantation.

Results: In all in vitro experiments, the small-diameter artificial blood vessel exhibited excellent biocompatibility and hemocompatibility. Furthermore, in vivo transplantation experiments demonstrated favorable anti-thrombotic properties and minimal intimal hyperplasia. And the small-diameter artificial blood caused no evident inflammatory reaction in tissue in vivo implantation experiments. What’s more, single-cell RNA sequencing revealed that endothelial cells (ECs), vascular smooth cells (SMCs), and myeloid cells were the main cell type in the small-diameter artificial blood, and endothelial-to-mesenchymal transition (EndMT) occurred. RNA velocity showed that ECs subtype transitions from quiescent to proliferating phenotype

Conclusion: The biomimetic small-diameter artificial blood vessel has potential clinical application prospects, and the results of single-cell RNA sequencing provide support for its optimization and clinical translation.

Abstract :

Today, the recipe for mayonnaise sauces is constantly evolving, considering the high global consumption of mayonnaise products and modern concerns about their health value, along with improving the quality of food products. In addition to emulsion products, we can increase the preventive properties of mayonnaise by enriching it with biological substances and functional oils. In the ongoing scientific research, we have studied the proximal analysis and toxicological evaluation of prepared mayonnaise based on new patented biologically active substances, and it has been determined that it has beneficial properties. Based on the latest recipe, the widely-used starch component, was replaced with sesame, and lemon peel was added as a natural antioxidant. Compared to the conventional mayonnaise recipe, fortified mayonnaise has a higher protein and lower fat content, offering a healthier product with functional properties. In addition, fresh mayonnaise has lower peroxide and anisidine values, indicating higher resistance to oxidative damage. Mayonnaise enriched with biologically active raw materials, sesame, and lemon peel proved safe in the conducted studies and met safety requirements regarding toxicological parameters.

Keywords: Mayonnaise; Sesame meal; Lemon zest; Emulsion system

Abstract:

Sperm-associated antigen 6 (SPAG6) is the mammalian orthologue of Chlamydomonas PF16, a protein localizing within the central pair of the axoneme and involved in flagellar motility of the algae. In mice, two Spag6 genes have been identified. The ancestral gene, located on mouse chromosome 2, is named Spag6. A related gene, located on mouse chromosome 16 and evolved from the ancient Spag6 gene, has been named Spag6-like (Spag6l). Global Spag6 knockout mice (C57 background) are grossly normal, and fertility was not shown to be affected in both males and females. In particular, the homozygous males had normal sperm parameters, including sperm count, motility, and morphology. Examination of testis histology also revealed normal spermatogenesis. In contrast, the global Spag6l knockout mouse model (C57 background) was previously generated and showed lethality. Most homozygous Spag6l knockout mice died before 4-weeks of age; the few males which survived to sexual maturity were infertile, and the fertility of the females was also affected. However, fertility of the heterozygous Spag6l knockout mice was normal.  We have crossed the two knockout lines to generate Spag6/Spag6l double knockout mice. The compound heterozygous (Spag6^+/-; Spag6l^+/-) mice showed normal fertility, and all the mice carrying Spag6l homozygous mutation (Spag6l^-/-), either with heterozygous (Spag6^+/-) or homozygous (Spag6^-/-) Spag6 mutation died before 4-weeks of age. However, even though all Spag6^-/-; Spag6l^+/- mice were grossly normal, all the males were completely infertile. Compared to the controls (Spag6^-/-; Spag6l^+/+ or Spag6^+/-; Spag6l^+/-) males, the Spag6^-/-; Spag6l^+/- males had significantly reduced sperm number, and the sperm that were formed were morphologically abnormal and motility was significantly reduced. Histologic examination of the testes by light microscopy also revealed impaired spermiogenesis. Analysis by Transmission Electron Microscopy revealed abnormal sperm ultrastructure with both head/chromatin and tail formation defects. The Spag6^-/-; Spag6l^+/- females sired normal number of pups compared to the control females but the time from breeding to delivery was longer than normal, suggesting gestation defects. Overall, our findings indicate that in mouse, both genes, Spag6 and Spag6l, coordinate to modulate sperm formation and male fertility and are also likely required for proper female fertility.