Results: We identified 4 shared FSP neoantigens (Nacad [FSP-1], Maz [FSP-1], Senp6 [FSP-1], Xirp1 [FSP-1]) that induced CD4/CD8 T cell responses in naïve C57BL/6 mice. Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival. Combination of FSP vaccination with daily naproxen treatment potentiated immune response, delayed tumor growth, and prolonged survival even more effectively than FSP vaccination alone.
Vera Ls Model 3 Sets 1
Gain control of care delivery, improve patient health outcomes, and reduce total cost of care through our value-based care model that provides a better end-to-end experience for everyone.
Figure 3. The results of the AIC, BIC values of German test. Simple 1 and Simple 2 show uncorrelated and correlated simple structure, Uni-German shows unidimensional German test, all models were estimated with 2PL model.
Figure 9. Pearson correlations between subtest scores and German test scores (test scores estimated with the MAP method) and correlations between general factor scores and scores estimated with specific factors were indicated. Symbols used in the matrix were indicated as follows: G, general factor; S, specific factor; R, Rasch model; 2, two-parameter model.
Skin burn wound is a notable medical burden worldwide. Rapid and effective treatment of burnt skin is vital to fasten wound closure and healing properly. Amniotic graft and Aloe vera are widely used as wound managing biomaterials. Sophisticated processing, high cost, availability, and the requirement of medics for transplantation limit the application of amnion grafts. We aim to prepare a novel gel from amnion combined with the Aloe vera extract for burn wound healing which overcome the limitations of graft.
Two percent human amniotic membrane (AM), Aloe vera (AV) and AM+AV gels were prepared. In vitro cytotoxicity, biocompatibility, cell attachment, proliferation, wound healing scratch assays were performed in presence of the distinct gels. After skin irritation study, second-degree burns were induced on dorsal region of Wistar rats; and gels were applied to observe the healing potential in vivo. Besides, macroscopical measurement of wound contraction and re-epithelialization; gel treated skin was histologically investigated by Hematoxylin and eosin (H&E) staining. Finally, quantitative assessment of angiogenesis, inflammation, and epithelialization was done.
We demonstrated that a gel consisting of a combination of amnion and Aloe vera extract has high efficacy as a burn wound healing product. Amniotic membrane combined with the carrier Aloe vera in gel format is easy to produce and to apply.
Human amniotic membrane graft is one of the most medically accepted and widely used biomaterials in burn wound healing treatment from 1910 on [17, 18]. It acts as a scaffold for proliferation and differentiation of new epithelial cells due to presence of factors such as fibronectin, elastin, nidogen, collagen types I, III, IV, V, VI, and hyaluronic acid [19,20,21]. Alongside lacking of histocompatibility antigens HLA-A, B and DR [22], it possesses an anti-inflammatory effect [23]. However, the processing, transportation and storage of intact thin sheet of amniotic membrane has limited clinical applications due to associated cost. In 2017, the Atala group reported that dissolved amniotic membrane with hyaluronic acid gel can speed up the skin wound healing process [24]. Besides the human materials, plants extract are also experimented to have burn healing properties. For instance, Aloe vera (AV) has been used in treating burn associated wound and observed to be effective in burn wound management [25, 26]. Because of anti-inflammatory effects, AV is of high usefulness in the treatment of skin wounds and first to second degree burns [27]. Additionally, AV treatment significantly increased the collagen synthesis and remodels collagen composition (type III) to promote wound healing, contraction and the breaking strength of resulting scar tissue [28, 29]. Importantly, it has been demonstrated that AV has greater efficacy over silver sulfadiazine cream in the treatment of second-degree burns [30, 31]. In the developed world, recombinant growth factors and cellular tissue-engineered skin substitutes-based wound treatments are available and clinically practiced [32]. However, this sophisticated approach is associated with high costs for patients in the low-income countries [33]. Some reported commercial skin grafts such as integra and biobrane are available which have been shown to improve wound healing but they are also expensive and sometimes do not deliver optimal outcomes [34, 35]. Thus, there is a need for a wound healing product with high clinical efficiency, which can be used rapidly, but retains the activity of a biological treatment.
Clinically, amnion has been applied as a wound covering bioactive material to heal split thickness skin burn wounds as well as for children with partial-thickness facial burns [36, 37]. From our experience, amniotic membrane as a graft for burn wounds enclosure in Bangladesh appears to be advantageous [38]. But the limited number of membrane donors and the lack of trained personnel in amniotic graft processing are major challenges. Further, amniotic membrane grafting service is available only in city areas at a very limited scale. Other limitations including instant requirement of physicians to do the transplantation of the graft and the sheet of amnion is generally held in place with sutures or additional bandaging [24]. Considering the described treatment limitations on the one side and the advantages of wound healing properties of human amnion and Aloe vera on the other side; this study aimed to develop a novel cost efficient product which in fact should be easy to produce and to store, physiologically effective and which application does not require a medic. Thus, we prepared three novel gel products from the extract of amniotic membrane (AM), Aloe vera (AV) and the combination (AM+AV) which were later characterized both in vitro and in vivo. We have demonstrated the usefulness of AM, AV and AM+AV gels as wound healing biomaterials which can accelerate burn wound closure through contraction, re-epithelialization, reduced inflammation and increasing angiogenesis in an animal model for skin burn.
Donated full term human placentas were collected during cesarean sections, the erythrocytes were depleted and the amnion was separated (Fig. 1a1-a6) for further processing. Afterwards, amniotic membranes were lyophilized, gamma irradiated, blended and finally freeze-dried to obtain powder (Fig. 1a7-a9). The juice of fresh Aloe vera leaves was collected and freeze-dried to extract powder for further use (Fig. 1b1-b2).
Processing of amnion membrane and Aloe vera and physical appearance of the formulated gels. a Preparation of amniotic membrane from human placenta (a1, a2, a3, a4, a5 and a6). The dried lyophilized amniotic membrane was 10KGy gamma irradiated and blended. Then the freeze-dried powder was used to formulate AM gel (a7, a8, a9 and a10). b Aloe vera leaves (b1) and freeze-dried Aloe vera extracted powder (b2). The formulated gels AM, AV and AM + AV were shown in a10, a3, and c respectively
The obtained amnion (AM) and Aloe vera (AV) powders were used to formulate the 2% gels (AM, AV and AM+AV) as described in methods section. The pH of all three gel formulations was measured and ranged from 6.5 to 6.9 (AM 6.7, AV 6.5 and AM+AV 6.9). All formulated gels were found to be semi-solid and homogeneous in nature. The color of the AV gel was off-white while the AM and AM+AV gels were yellowish white whereas all gels were semi-transparent (Fig. 1a10, b3, c).
Amniotic membrane has been reported to provide a niche for the cells to adhere, grow, proliferate, migrate and differentiate, and could possibly contribute to the production of angiogenic micro-environment indirectly which allows AM to improve burn healing [58]. We found that a combination of both AM and AV synergistically improved epithelialization. On day 30, epithelialization profile was significantly higher in the AM+AV group. Amniotic membrane is composed of collagen type IV, V and VII which promotes growth of epithelial cells, facilitates epithelial cell migration, strengthens basal epithelial cell adhesion, promotes differentiation of epithelial cell, and prevents apoptotic cell death [59]. In principal, we have prepared gels from medically discarded materials, at low cost that provides excellent burn wound coverage. These formulated gels showed potential to be used as fast aid ointment in burn wound management. Although we demonstrated significant improvement of burn wound healing in rats treated with AM+AV gel, however, some limitations are associated with this animal model such as the remarkable native regeneration potential of the rat skin. For future application, it would be crucial to identify the key factors in the amnion that are responsible for the acceleration of the wound healing process.
Taken together the in vitro and in vivo data, our findings clearly demonstrate that amniotic membrane combined with Aloe vera extract significantly enhances burn wound healing, thus indicating that the amniotic membrane and Aloe vera possesses potent wound healing activities. Amniotic membrane is a globally accepted biological biomaterial for second and third degree burn. Aloe vera gel has been reported to have burn healing capacity as well. The combination of both AM and AV has been shown to have promising effect in internal epithelialization with less scar formation. Gels containing AM extract individually and in combination with AV could be used alternatively in the treatment of burn. However, further investigation is required to assess optimal concentration of the used extracts and key factors present in AM and AV to find out the best combination for burn healing. Moreover, it is also of great importance to unfold the underlying molecular mechanisms. As a further investigation step, cell based therapies using skin progenitor cells in combination with the tested gels, could be another way to accelerate wound healing. 2ff7e9595c
Comentários