Cold atmospheric plasma induces the curing mechanism of diabetic wounds by regulating the oxidative stress mediators iNOS and NO, the pyroptotic mediators NLRP-3, Caspase-1 and IL-1ß and the angiogenesis mediators VEGF and Ang-1.

It has been demonstrated that cold atmospheric plasma (CAP) accelerates the wound healing process, however the underlying molecular pathways behind this effect remain unclear. Thus, the goal of the proposed investigation is to elucidate the therapeutic advantages of CAP on angiogenesis, pyroptotic, oxidative stress, and inflammatory mediators during the wound-healing mechanisms associated with diabetes. Intraperitoneal administration of streptozotocin (STZ, 60 mg/Kg) of body weight was used to induce type-1 diabetes. Seventy-five male mice were randomized into 3 groups: the control non-diabetic group, the diabetic group that was not treated, and the diabetic group that was treated with CAP. The key mediators of pyroptosis and its impact on the slow healing process of diabetic wounds were examined using histological investigations employing H&E staining, immunohistochemistry, ELISA, and Western blotting analysis. Angiogenesis proteins (VEGF, Ang-1, and HO-1) showed a significant decline in expression concentrations in the diabetic wounds, indicating that diabetic animals' wounds were less likely to heal. Furthermore, compared to the controls, the major mediators of pyroptosis (NLRP-3, IL-1ß, and caspase-1), oxidative stress (iNOS and NO), and inflammation (TNF-α and IL-6) have higher expression levels in the diabetic wounds. These factors substantially impede the healing mechanism of diabetic wounds. Interestingly, our results disclosed the therapeutic impacts of CAP treatment in the healing process of diabetic wounds via significantly regulating the expression levels of angiogenesis, pyroptosis, oxidative stress and pro-inflammatory mediators. Our findings demonstrated the curative likelihood of CAP and the underlying mechanisms for enhancing the healing process of diabetic wounds.

Bee gomogenat enhances the healing process of diabetic wounds by orchestrating the connexin-pannexin gap junction proteins in streptozotocin-induced diabetic mice.

Delay in wound healing remains one of diabetes's worse side effects, which increases mortality. The proposed study sought to scrutinize the implications of bee gomogenat (BG) on diabetic's wound closure in a streptozotocin-(STZ)-enhanced type-1 diabetes model's rodents. We used 3 different mice groups: group 1 non-diabetic rodents "serving as control", group 2 diabetic rodents, and group3 BG-treated diabetic rodents. We noticed that diabetic rodents experience a delayed wound closure, which emerged as a significant (*P < 0.05) decline in the deposition of collagen as compared to control non-diabetic animals. We noticed that diabetic rodents have a delayed wound closure characterized by a significant (*P < 0.05) decrease in the CD31 expression (indicator for wound angiogenesis and neovascularization) and an apparent elevation in the expression of such markers of inflammation as MCP-1 and HSP-70 as compared to control animals. Moreover, diabetic animals displayed a significant (*P < 0.05) increase in the expression of gap junction proteins Cx43 and a significant decrease in the expression of Panx3 in the wounded skin tissues when compared to the controls. Intriguingly, topical application with BG on the diabetic wounded skin tissues contributes to a significant (#P < 0.05) enhancing in the collagen deposition, up-regulating the level of CD31 expression and a significant (#P < 0.05) down-regulation in the MCP-1 and HSP-70 expressions as compared to diabetic non-treated animals. The expression's levels of Cx43 and Panx3 were significantly (#P < 0.05) retrieved in diabetic rodents after BG treatment. Taken together, our findings showed for the first time that BG promotes the recovering process and accelerated the closure of diabetic related wounds.

Bee gomogenat rescues lymphoid organs from degeneration by regulating the crosstalk between apoptosis and autophagy in streptozotocin-induced diabetic mice.

Diabetes mellitus (DM) is a metabolic disorder that causes severe complications in several tissues due to redox imbalances, which in turn cause defective angiogenesis in response to ischemia and activate a number of proinflammatory pathways. Our study aimed to investigate the effect of bee gomogenat (BG) dietary supplementation on the architecture of immune organs in a streptozotocin (STZ)-induced type 1 diabetes (T1D) mouse model. Three animal groups were used: the control non-diabetic, diabetic, and BG-treated diabetic groups. STZ-induced diabetes was associated with increased levels of blood glucose, ROS, and IL-6 and decreased levels of IL-2, IL-7, IL-4, and GSH. Moreover, diabetic mice showed alterations in the expression of autophagy markers (LC3, Beclin-1, and P62) and apoptosis markers (Bcl-2 and Bax) in the thymus, spleen, and lymph nodes. Most importantly, the phosphorylation level of AKT (a promoter of cell survival) was significantly decreased, but the expression levels of MCP-1 and HSP-70 (markers of inflammation) were significantly increased in the spleen and lymph nodes in diabetic mice compared to control animals. Interestingly, oral supplementation with BG restored the levels of blood glucose, ROS, IL-6, IL-2, IL-4, IL-7, and GSH in diabetic mice. Treatment with BG significantly abrogated apoptosis and autophagy in lymphoid organs in diabetic mice by restoring the expression levels of LC3, Beclin-1, P62, Bcl-2, and Bax; decreasing inflammatory signals by downregulating the expression of MCP-1 and HSP-70; and promoting cell survival by enhancing the phosphorylation of AKT. Our data were the first to reveal the therapeutic potential of BG on the architecture of lymphoid organs and enhancing the immune system during T1D.

Molecular mechanisms underlying antitumor activity of camel whey protein against multiple myeloma cells.

Treating drug-resistant cancer cells is a clinical challenge and it is also vital to screen for new cancer drugs. Multiple myeloma (MM) is a plasma cell clonal cancer that, despite many experimental therapeutics, remains incurable. In this study, two MM cell line lines U266 and RPMI 8226 were used to determine the impact of camel whey protein (CWP). The CWP IC50 was calculated by MTT examination, while the flow cytometry analysis was used to investigate the chemotaxis responses of MM cells in relation to CXCL12 and the pro-apoptotic effect of CHP. MM cells were treated with CWP and Western blot analysis was used to determine the underlying molecular mechanisms. Dose and time based on the impact of CWP on the cell viability of MM cells with IC50 of 50 µg/ml, without affecting the viability of normal healthy PBMCs. CWP reduced chemotaxis of MM cells significantly from the CXC chemokine ligand 12 (CXCL12). Using Western blot analysis, we found that CWP decreased the activation of AKT, mTOR, PLCß3, NFαB and ERK, which was mechanistically mediated by CXCL12/CXCR4. In both U266 and RPMI 8226, CWP induced apoptosis by upregulating cytochrome C expression. In addition, CWP mediated the growth arrest of MM cells by robustly decreasing the expression of the anti-apoptotic Bcl-2 family members Bcl-2, Bcl-XL and Mcl-1. Conversely, the expression of pro-apoptotic Bcl-2 family members Bak, Bax and Bim was increased after treatment with CWP. Our data indicates CWP's therapeutic potential for MM cells.

Why whey? Camel whey protein as a new dietary approach to the management of free radicals and for the treatment of different health disorders.

The balance between free radicals and antioxidants is an important factor for maintaining health and slowing disease progression. The use of antioxidants, particularly natural antioxidants, has become an important strategy for dealing with this cause of widespread diseases. Natural antioxidants have been used as therapeutic tools against many diseases because they are safe, effective, and inexpensive and are among the most commonly used adjuvants in the treatment of several diseases. Camel whey protein (CWP) is considered a strong natural antioxidant because it decreases oxidative stress, enhances immune system function, and increases glutathione levels. The structure of CWP is very similar to that of other types of whey protein from different types of milk. CWP contains many components, such as lactoferrin (LF), lactalbumin, lactoglobulins, lactoperoxidase, and lysozyme, and is rich in immunoglobulins. However, in contrast to other WPs, CWP lacks ß-lactoglobulin, the main cause of milk allergies in children. The components of CWP have many beneficial effects, including stimulation of both innate and adaptive immunity and anti-inflammatory, anticancer, antibacterial, and antiviral activities. Recently, it has been shown that CWP and its unique components can facilitate the treatment of impaired diabetic wound healing. However, the molecular mechanisms underlying the protective effects of CWP in human and other animal disorders are not fully understood. Therefore, the current review presents a concise summary of the scientific evidence of the beneficial effects of CWP to support its therapeutic use in disease treatment and nutritional intervention.

Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice.

BACKGROUND: Diabetes mellitus (DM) is associated with severe immune system complications. Camel whey protein (CWP) decreases free radicals (ROS) and modulates immune functions, but its effect on DM-impaired immune systems has not been studied. We investigated the impact of CWP on the immune system in a Type 1 diabetes mouse model. METHODS: Three experimental groups were used: (1) non-diabetic control; (2) diabetic; and (3) CWP-treated diabetic mice. RESULTS: Induction of diabetes by streptozotocin was associated with reduction of body weight and insulin level, increase in glucose level and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), and reduction in IL-2 and IL-4 levels. Upregulated ATF-3 expression was followed by a marked elevation in ROS levels. Lymphocytes from diabetic mice exhibited increased apoptosis through decreased phosphorylation of AKT and IκB-α, increased infiltration of T cells in the spleen and thymus, and decreased B cell numbers in the spleen. Supplementation with CWP decreased the levels of proinflammatory cytokines, ROS, and ATF-3 expression, and increased the levels of IL-4. Treatment with CWP decreased apoptosis by enhancing the phosphorylation of AKT and IκB-α as well as T-cell and B-cell distribution in the spleen and thymus. CONCLUSIONS: Our findings suggest the beneficial effects of CWP supplementation during diabetes on decreasing and orchestrating the redox status and subsequently rescuing the immune cells from exhaustion.

Camel whey protein improves oxidative stress and histopathological alterations in lymphoid organs through Bcl-XL/Bax expression in a streptozotocin-induced type 1 diabetic mouse model.

Type I diabetes (T1D) is a characterized by the inflammation of pancreatic islets and destruction of ß cells. Long and persistent uncontrolled diabetes tends to degenerate the immune system and increase the incidence of infections in diabetic individuals. Most serious diabetic complications are mediated by the free radicals, which damage multiple cellular components through direct effects of the cell cycle regulatory proteins. Camel whey protein (CWP) has antioxidant activity and decreases the effects of free radicals. However, the effects of CWP on lymphoid organs have not been studied in the context of diabetes. Therefore, the present study was designed to investigate the dietary influence of CWP supplementation on the lymphoid organs in streptozotocin (STZ)-induced type 1 diabetic mouse model. Three experimental groups were used: non diabetic control mice, diabetic mice, and diabetic mice treated with CWP. Induction of diabetes was associated with a marked reduction in glutathione (GSH) levels; decreased activities of GSH peroxidase (GSH Px), manganese superoxide dismutase (MnSOD) and catalase; increased reactive oxygen species (ROS) levels and iNOS activity in plasma and lymphoid organs. Furthermore, diabetic mice exhibited alterations in the expression of Bax and Bcl-XL, and subsequently pathological alterations in the architecture of the bone marrow, pancreas, thymus, and spleen. Interestingly, treatment of diabetic mice with CWP robustly restored glucose, insulin, GSH, and ROS levels and the activities of GSH Px, MnSOD, catalase and iNOS. Additionally, supplementation of diabetic mice with CWP improvement in the architecture of lymphoid tissues and rescued from apoptosis through direct effects on the Bax and Bcl-XL proteins. These data revealed the therapeutic potential of CWP against diabetic complications mediated damages of lymphoid organs.