MUC1 regulation in the left and right uterine horns and conceptus trophectoderm during the peri-implantation period of dromedary camel.

Pregnancy maintenance in dromedary camels poses significant challenges, including early embryonic loss in the left uterine horn (LH) and unsuccessful pregnancy in the right uterine horn (RH), suggesting a potential asynchrony between conceptus signaling and uterine receptivity. The transition of the uterine epithelium from a pre-receptive to a receptive state requires a delicate balance of adhesion-promoting and anti-adhesion molecules. Mucin-1 (MUC1) acts as an anti-adhesive molecule on the uterine luminal (LE) and glandular (GE) epithelium. Downregulation of MUC1 is believed to be crucial for successful embryo attachment in various mammals. This study aimed to investigate the temporospatial expression of MUC1 in the LH and RH on Days 8, 10, and 12 pregnant dromedaries and their conceptuses. Quantitative real-time polymerase chain reaction (qrt-PCR), Western blot analysis, immunohistochemistry, and immunofluorescence techniques were employed to assess MUC1 expression at the mRNA and protein levels. The results demonstrated a reduction in MUC1 mRNA expression on Day 8, then increased on Day 10, followed by a decrease on Day 12 in LH. While the RH exhibited progressive increases, peaking on Day 12. However, MUC1 expression constantly exhibited higher levels in RH than in LH in all days. Two bands were detected at 150-kDa and 180-kDa, with the highest intensity observed on Day 10. Spatially, MUC1 was localized in the apical, cytoplasmic, and lumen of uterine glands only. MUC1 was barely detectable on Day 8 but gradually increased on Days 10 and 12 in both horns. Likewise, the RH exhibited higher MUC1 signals than the LH on Days 10 and 12. In the conceptuses, MUC1 mRNA increased on Day 8, peaked on Day 10, and declined on Day 12. Notably, MUC1 protein was detected in both the trophectoderm and endoderm, with high expression observed on Day 10 and reduced by Day 12. In conclusion, the decrease in MUC1 expression on Day 8 in the LH may be associated with maternal recognition of pregnancy (MRP), and the increase on Day 10 may related to embryo protection and movement, while the subsequent decrease on Day 12 could be linked to the embryo attachment and preparation for the implantation. Conversely, the increase of MUC1 in the RH implies a role in the anti-adhesion mechanism. These findings contribute to understanding MUC1's involvement in reproductive processes and provide insights into the complex mechanisms underlying successful pregnancy establishment and maintenance in dromedary camels.

Digestive properties and peptide profiles exhibited significant differences between skim camel milk and bovine milk powder after static in vitro simulated infant gastrointestinal digestion.

This study aims to analyze the differences in digestion properties and peptide profiles between the skim camel and bovine milk powder after static in vitro simulated infant gastrointestinal digestion. The hydrolysis degree of camel milk proteins exceeded by 13.18% that of bovine milk. The concentration and release rate of free amino groups in the camel milk digesta was higher than that of bovine milk powder, which was likely due to the higher ß-/αs-casein ratio and larger casein micelle size in camel milk. Camel milk powder presented higher ß-CN coverage and comparatively shorter bioactive peptides compared to bovine milk powder. The anti-inflammatory peptide KVLPVPQ displayed the highest abundance in camel milk powder. Outcomes of this study showed that camel milk proteins possessed superior digestibility and unique peptides, which outlined the potential nutritional implications of camel milk for infants.

Invited review: Camel milk-derived bioactive peptides and diabetes-Molecular view and perspectives.

In dairy science, camel milk (CM) constitutes a center of interest for scientists due to its known beneficial effect on diabetes as demonstrated in many in vitro, in vivo, and clinical studies and trials. Overall, CM had positive effects on various parameters related to glucose transport and metabolism as well as the structural and functional properties of the pancreatic ß-cells and insulin secretion. Thus, CM consumption may help manage diabetes; however, such a recommendation will become rationale and clinically conceivable only if the exact molecular mechanisms and pathways involved at the cellular levels are well understood. Moreover, the application of CM as an alternative antidiabetic tool may first require the identification of the exact bioactive molecules behind such antidiabetic properties. In this review, we describe the advances in our knowledge of the molecular mechanisms reported to be involved in the beneficial effects of CM in managing diabetes using different in vitro and in vivo models. This mainly includes the effects of CM on the different molecular pathways controlling (1) insulin receptor signaling and glucose uptake, (2) the pancreatic ß-cell structure and function, and (3) the activity of key metabolic enzymes in glucose metabolism. Moreover, we described the current status of the identification of CM-derived bioactive peptides and their structure-activity relationship study and characterization in the context of molecular markers related to diabetes. Such an overview will not only enrich our scientific knowledge of the plausible mode of action of CM in diabetes but should ultimately rationalize the claim of the potential application of CM against diabetes. This will pave the way toward new directions and ideas for developing a new generation of antidiabetic products taking benefits from the chemical composition of CM.

Bioactive peptides in hydrolysates of bovine and camel milk proteins: A review of studies on peptides that reduce blood pressure, improve glucose homeostasis, and inhibit pathogen adhesion.

The prevalence of diet-related chronic conditions including hypertension and cardiovascular disease, and diabetes mellitus has increased worldwide. Research regarding the use of food-derived bioactive peptides as an alternative strategy to mitigate chronic diseases is on the rise. Milk is recognized as one of the main dietary protein sources for health beneficial bioactive compounds. Hundreds of in vitro studies have suggested that milk-derived bioactive peptides offer multiple biological and physiological benefits, and some but not all were confirmed in vivo with animal models for hypertension, hyperglycemia, and pathogen adhesion. However, only a limited number of health benefits have been confirmed by randomized clinical trials. This review provides an overview of the current clinical studies that target hypertension, postprandial hyperglycemic, and adhesion of enteric pathogen with bioactive peptides derived from bovine and camel milk, with a focus on the factors affecting the efficacy of orally ingested products.

Development of a Functional Nanobody Targeting Programmed Cell Death Protein-1 as Immune Checkpoint Inhibitor.

BACKGROUND: Programmed cell death protein 1 (PD-1) is a membrane receptor that is expressed on the surface of various immune cells, such as T cells, B cells, monocytes, natural killer T cells, and dendritic cells. In cancer, the interaction between PD-1 and its ligand PD-L1 suppresses the activation and function of T lymphocytes, leading to the impairment and apoptosis of tumor-specific T cells. This mechanism allows cancer cells to evade the immune response and promotes tumor progression. METHODS: Recombinant PD-1 protein was produced and used to immunize a camel. A nanobody library was generated from the camel's peripheral blood lymphocytes and screened for PD-1 binding. A specific nanobody (3PD9) was selected and characterized by affinity measurement, western blotting, and flow cytometry analysis. The ability of the selected nanobody to block the inhibitory signal of PD-1 in peripheral blood mononuclear cells (PBMCs) was evaluated by measuring the level of interleukin-2 (IL-2). RESULTS: The selected nanobody showed high specificity and affinity for human PD-1. Western blot and flow cytometry analysis confirmed that 3PD9 could recognize and bind to human PD-1 on the cell surface. It was demonstrated that the level of IL-2 was significantly increased in PBMCs treated with 3PD9 compared to the control group, indicating that the nanobody could enhance the T cell response by disrupting the PD-1/PD-L1 interaction. CONCLUSION: The results suggested that the anti-PD-1 nanobody could be a promising candidate for cancer immunotherapy.

Molecular binding mechanism and novel antidiabetic and anti-hypertensive bioactive peptides from fermented camel milk with anti-inflammatory activity in raw macrophages cell lines.

The investigation was to determine the effect of camel milk fermented with Limosilactobacillus fermentum KGL4 (MTCC 25515) on ACE-inhibiting, anti-inflammatory, and diabetes-preventing properties and also to release the novel peptides with antidiabetic and anti-hypertensive attributes with molecular interaction studies. Growth conditions were optimised on the basis of total peptide production by inoculating the culture in camel milk at different rates (1.5, 2.0, and 2.5%) along with different incubation periods (12, 24, 36, and 48 h). However, after 48 h of fermentation with a 2.5% rate of inoculum, the highest proteolytic activity was obtained. Reverse phase high-pressure liquid chromatography (RP-HPLC) was used to calculate the % Rpa from permeates of 3 kDa and 10 kDa fractions. Molecular weight distributions of fermented and unfermented camel milk protein fractions were compared using SDS-PAGE. Spots obtained from 2D gel electrophoresis were separated on the basis of pH and molecular weight. Spots obtained from 2D gel were digested with trypsin, and the digested samples were subjected to RP-LC/MS for the generation of peptide sequences. The inhibition of tumour necrosis factor alpha, interleukin-6, and interleukin-1 during fermentation was studied using RAW 264.7 macrophages. In the study, fermented camel milk with KGL4 (CMKGL4) inhibited LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1ß) by the murine macrophages. The results showed that the peptide structures (YLEELHRLNK and YLQELYPHSSLKVRPILK) exhibited considerable binding affinity against hPAM and hMGA during molecular interaction studies.

Use of 4-D proteomics to differentiate between bovine and camel lactoferrin.

Lactoferrin is a multifunctional protein that has various biological activities and applications. However, different sources of lactoferrin may have different properties and characteristics. In this study, we hypothesized that ultra-performance liquid chromatography quadrupole time-of-flight mass spectroscopy (UPLC-QTOF-IMS) coupled with UNIFI software can differentiate bovine lactoferrin from camel lactoferrin based on the unique peptides produced by trypsin digestion. We enzymatically digested the proteins using trypsin and analyzed the resulting peptides using Uniport software and in silico digestion. We identified 14 marker peptides that were unique to bovine lactoferrin and could be used to distinguish it from camel lactoferrin. We also demonstrated the advantages of 4D proteomics over 3D proteomics in separating and identifying peptides based on their mass, retention time, intensity, and ion mobility. This method can be applied to other lactoferrin sources and improve the quality control and authentication of lactoferrin products.

In-depth peptidomic profile and molecular simulation studies on ACE-inhibitory peptides derived from probiotic fermented milk of different farm animals.

Investigations into ACE inhibitory properties of probiotic fermented bovine, camel, goat, and sheep milk were performed and studied for two weeks of refrigerated storage. Results from the degree of proteolysis suggested higher susceptibility of goat milk proteins, followed by sheep and camel milk proteins, to the probiotic-mediated proteolysis. ACE-inhibitory properties displayed continuous decline in ACE-IC50 values for two weeks of refrigerated storage. Overall, goat milk fermented with Pediococcus pentosaceus caused maximum ACE inhibition (IC50: 262.7 µg/mL protein equivalent), followed by camel milk (IC50: 290.9 µg/mL protein equivalent). Studies related to peptide identification and in silico analysis using HPEPDOCK score revealed presence of 11, 13, 9 and 9 peptides in fermented bovine, goat, sheep, and camel milk, respectively, with potent antihypertensive potential. The results obtained suggest that the goat and camel milk proteins demonstrated higher potential for generating antihypertensive peptides via fermentation when compared to bovine and sheep milk.

In vitro antidiabetic and antihypercholesterolemic activities of camel milk protein hydrolysates derived upon simulated gastrointestinal digestion of milk from different camel breeds.

Milk protein hydrolysates derived from 4 camel breeds (Pakistani, Saheli, Hozami, and Omani) were evaluated for in vitro inhibition of antidiabetic enzymatic markers (dipeptidyl peptidase IV and α-amylase) and antihypercholesterolemic enzymatic markers (pancreatic lipase and cholesterol esterase). Milk samples were subjected to in vitro simulated gastric (SGD) and gastrointestinal digestion (SGID) conditions. In comparison with intact milk proteins, the SGD-derived milk protein hydrolysates showed enhanced inhibition of α-amylase, dipeptidyl peptidase IV, pancreatic lipase, and cholesterol esterase as reflected by lower half-maximal inhibitory concentration values. Overall, milk protein hydrolysates derived from the milk of Hozami and Omani camel breeds displayed higher inhibition of different enzymatic markers compared with milk protein hydrolysates from Pakistani and Saheli breeds. In vitro SGD and SGID processes significantly increased the bioactive properties of milk from all camel breeds. Milk protein hydrolysates from different camel breeds showed significant variations for inhibition of antidiabetic and antihypercholesterolemic enzymatic markers, suggesting the importance of breed selection for production of bioactive peptides. However, further studies on identifying the peptides generated upon SGD and SGID of milk from different camel breeds are needed.

Significance of Lactobacillus fermentum on Antioxidative and Anti-Inflammatory Activities and Ultrafiltration Peptide Fractions as Potential Sources of Antioxidative Peptides from Fermented Camel Milk (Indian Breed).

OBJECTIVE: The present study aimed to assess the bio-functional analysis of camel milk viz. anti-oxidative, anti-inflammatory activities using potent Lactobacillus fermentum (KGL4) strain through fermentation and also to release the bioactive peptides during fermentation. METHOD: The antioxidant and proteolytic activities of the fermented camel milk were studied followed by SDS-PAGE analysis and 2 D PAGE. The separations of the bioactive peptides of water-soluble extract (WSE) of 3 and 10 kDa (Permeates & Retentates) were achieved by RP-HPLC. The purified bioactive peptides were identified and characterized using RPLC/MS and the effect of WSE of camel milk fermented with KGL4 on lipopolysaccharide (LPS)/endotoxin-induced inflammation in RAW 264.7 macrophages were also studied. RESULTS: The maximal activity was observed in ABTS assay (64.03%), then in hydroxyl free radical scavenging assay, and minimal activity was observed in superoxide free radical assay (57.75%). ABTS assay was significantly (P < 0.05) higher than other assays. MTT assay was performed on WSE of camel milk fermented with KGL4 using treated macrophage cells with different concentrations and found the decreasing range of cell viability at 0.25 mg/mL treatment which was non-significant. 7.80 mg/ml peptide production was found after 48 h of fermentation using the OPA method. Further, WSE of fermented camel milk was separated and analyzed their protein profiles using SDS-PAGE and 2 D-PAGE techniques. Here, many new peptides were found in camel milk when fermented with KGL4 strain. Each protein sequence was characterized through bioinformatic tools, including SWISS-PROT & PIR protein databases. Novel bioactive anti-oxidative peptides were found by searching in the BIOPEP database. CONCLUSIONS: The present study suggests that the L. fermentum KGL4 strain could be explored to produce novel antioxidative peptides from fermented camel milk (Indian breed).

Estimation of bioactive peptide content of milk from different species using an in silico method.

This study assessed the bioactive peptides content of milk from different species, including humans, camel, bovine, buffalo, donkey, sheep, goat, and horse. The highest and lowest concentrations of total digestion-resistant peptides were estimated in sheep and human milk. Donkey milk casein contains a higher angiotensin-converting enzyme (ACE) inhibitory, dipeptidyl peptidase III (DPP-III) inhibitory, DPP-IV inhibitory, and antioxidant peptides. On the other hand, camel whey protein contains the highest ACE-inhibitory peptides. To discover BPs with immunomodulatory and cholesterol-lowering functions, goat milk casein and sheep milk whey protein can be considered, respectively.

Early postmortem degradation of actin muscle protein in Algerian Sahraoui dromedaries.

The present study aimed to evaluate actin degradation during the early postmortem time in Longissimus Lumborum muscle according to Sahraoui dromedary's age. A sample of eight males, young (2 years old) and adult (8 years old) dromedaries, was used to investigate meat quality traits and actin proteolysis during the conversion of muscle to meat. Results demonstrated higher pH values in young compared to adult with a polyphasic pH drop profile. While, age did not affect drip loss (DL) and the values at 72 h postmortem varied from 5 to 9%. Western blot revealed that actin proteolysis occurred since 1 h postmortem and that it was affected by age and postmortem time. In particular, the 32 and 25 kDa actin fragments could be potential markers of ongoing meat tenderization.

Exploring the potential of Lacticaseibacillus paracasei M11 on antidiabetic, anti-inflammatory, and ACE inhibitory effects of fermented dromedary camel milk (Camelus dromedaries) and the release of antidiabetic and anti-hypertensive peptides.

The goal of this investigation was to find antidiabetic peptides and inhibit angiotensin converting enzyme (ACE) in Lacticaseibacillus paracasei (M11) fermented dromedary camel milk (Camelus dromedaries). According to the findings, the rate of antidiabetic activity increased along with the incubation periods and reached its peak after 48 hr of fermentation. The inhibitions of α-amylase, α-glucosidase, and lipase were 80.75, 59.62, and 65.46%, respectively. The inhibitory activity of ACE was 78.33%, and the proteolytic activity was 8.90 mg/mL. M11 at 0.25 mg/mL effectively suppressed LPS-induced pro-inflammatory cytokines and their mediators such as NO, TNF-α, IL-6, and IL-1ß in RAW 264.7 cells. The rate of inoculum in the optimization phase was 1.5-2.5%, and the greatest proteolytic activity was observed after 48 hr of fermentation. The investigation of the above property in the ultrafiltered fermented milk exhibited the highest antidiabetic and ACE inhibition activities in the 3 kDa than 10 kDa fractions. The molecular weight was determined employing SDS-PAGE, and the six-peptide sequences were identified using 2D gel electrophoresis. Due to its high proteolytic activity, the L. paracasei strain has been reported to be useful in the production of ACE-inhibitory and antidiabetic peptides. Amino acid sequences such from ɑ1, ɑ2, and ß-caseins have been identified within fermented camel milk by searching on online databases, including BIOPEP (for antidiabetic peptides) and AHTPDB (for hypertension peptides) to validate the antidiabetic and ACE-inhibitory actions of several peptides. PRACTICAL APPLICATIONS: The study aims to identify antidiabetic peptides and inhibit ACE in dromedary camel milk fermented with Lacticaseibacillus paracasei M11. Maximum antidiabetic and ACE-inhibitory actions of the fermented camel milk were observed in 3 kDa permeate fractions. Fermented camel milk significantly reduced the excessive TNF-α, IL-6, and IL-1ß production in LPS-activated RAW 264.7 cells. RP-LC/MS was used to identify 6 bioactive peptides from dromedary fermented camel milk. This fermented camel milk could be used for the management of hypertension and diabetic related problems.

Induced-ovulation in female dromedary camel involves kisspeptin neuron activation by ß nerve growth factor†.

The dromedary camel (Camelus dromedarius) is a short-day desert breeder in which female ovulation is induced by mating. Current data indicate that male-induced ovulation is triggered by its seminal plasma nerve growth factor beta (ß-NGF), but the exact mechanisms involved in the induction of ovulation are still unknown. In this study, we report that an intramuscular injection of ß-NGF in sexually active short-day-adapted female camels induces an ovulation attested by a surge of circulating LH (2-6 h after treatment) followed by an oocyte release with its cumulus oophorus (confirmed by ultrasonography 72 h after treatment) and a large and progressive increase in circulating progesterone (significant from the 2nd to the 10th days after ß-NGF injection). In addition, this ß-NGF treatment induces a broad nuclear c-FOS activation in cells located in various hypothalamic areas, notably the preoptic area, the arcuate nucleus, the dorso- and ventromedial hypothalamus, the paraventricular nucleus, and the supraoptic nucleus. A double immunostaining with neuropeptides known to be involved in the central control of reproduction indicates that ~28% kisspeptin neurons and 43% GnRH neurons in the proptic area, and ~10% RFRP-3 neurons in the dorso- and ventromedial hypothalamus are activated following ß-NGF injection. In conclusion, our study demonstrates that systemic ß-NGF induces ovulation in the female dromedary camel and indicates that this effect involves the central activation of hypothalamic neurons, notably the kisspeptin neurons.

Amyloid fibril formation by αS1- and ß-casein implies that fibril formation is a general property of casein proteins.

Caseins are a diverse family of intrinsically disordered proteins present in the milks of all mammals. A property common to two cow paralogues, αS2- and κ-casein, is their propensity in vitro to form amyloid fibrils, the highly ordered protein aggregates associated with many age-related, including neurological, diseases. In this study, we explored whether amyloid fibril-forming propensity is a general feature of casein proteins by examining the other cow caseins (αS1 and ß) as well as ß-caseins from camel and goat. Small-angle X-ray scattering measurements indicated that cow αS1- and ß-casein formed large spherical aggregates at neutral pH and 20°C. Upon incubation at 65°C, αS1- and ß-casein underwent conversion to amyloid fibrils over the course of ten days, as shown by thioflavin T binding, transmission electron microscopy, and X-ray fibre diffraction. At the lower temperature of 37°C where fibril formation was more limited, camel ß-casein exhibited a greater fibril-forming propensity than its cow or goat orthologues. Limited proteolysis of cow and camel ß-casein fibrils and analysis by mass spectrometry indicated a common amyloidogenic sequence in the proline, glutamine-rich, C-terminal region of ß-casein. These findings highlight the persistence of amyloidogenic sequences within caseins, which likely contribute to their functional, heterotypic self-assembly; in all mammalian milks, at least two caseins coalesce to form casein micelles, implying that caseins diversified partly to avoid dysfunctional amyloid fibril formation.

Bacillus amyloliquefaciens Enriched Camel Milk Attenuated Colitis Symptoms in Mice Model.

Fermented camel's milk has various health beneficial prebiotics and probiotics. This study aimed to evaluate the preventive efficacy of Bacillus amyloliquefaciens enriched camel milk (BEY) in 2-, 4- and 6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis mice models. To this end, the immune modulatory effects of Bacillus amyloliquefaciens (BA) on TNF-α challenged HT29 colon cells were estimated using the cell proliferation and cytokines ELISA method. BEY was prepared using the incubation method and nutritional value was quantified by comparing it to commercial yogurt. Furthermore, TNBS-induced colitis was established and the level of disease index, pathological scores, and inflammatory markers of BEY-treated mice using macroscopic and microscopic examinations, qPCR and immunoblot were investigated. The results demonstrate that BA is non-toxic to HT29 colon cells and balanced the inflammatory cytokines. BEY reduced the colitis disease index, and improved the body weight and colon length of the TNBS-induced mice. Additionally, Myeloperoxidase (MPO) and pro-inflammatory cytokines (IL1ß, IL6, IL8 and TNF-α) were attenuated by BEY treatment. Moreover, the inflammatory progress mRNA and protein markers nuclear factor kappa B (NFκB), phosphatase and tensin homolog (PTEN), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX-2) and occludin were significantly down-regulated by BEY treatment. Interestingly, significant suppression of PCNA was observed in colonic tissues using the immunohistochemical examination. Treatment with BEY increased the epigenetic (microRNA217) interactions with PCNA. In conclusion, the BEY clearly alleviated the colitis symptoms and in the future could be used to formulate a probiotic-based diet for the host gut health and control the inflammatory bowel syndrome in mammals.

SIRT1 Mediates Neuroprotective and Neurorescue Effects of Camel α-Lactalbumin and Oleic Acid Complex on Rotenone-Induced Parkinson's Disease.

Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder. Presently used therapies for PD have severe side effects and are limited to only temporary improvement. Therefore, a new therapeutic approach to treat PD urgently needs to be developed. α-Lactalbumin, the most abundant milk protein in camel milk, has been attributed to various medicinal properties. This study intended to investigate the neuroprotective efficacy of the camel α-lactalbumin and oleic acid (CLOA) complex. One mechanism postulated to underlie neuroprotection by the CLOA complex is the induction of silent information regulatory protein (SIRT1). SIRT1 is known to be involved in several pathological and physiological processes, and it has been suggested that SIRT1 plays a protective role in PD. Oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis are involved in PD pathogenesis. Our results revealed that SIRT1 inhibits oxidative stress by maintaining HIF-1α in a deacetylated state. SIRT1 upregulates the expression of FOXO3a and HSF-1, thus inhibiting apoptosis and maintaining the homeostasis of cellular proteins. Increased SIRT1 expression reduces the levels of TNF-α, IL-6, and IL-8, which in turn inhibits neuroinflammation. In addition to SIRT1, the CLOA complex also enhances the expression of survivin and leptin and promotes the survival of neuroblastoma cells. Altogether, our results suggest that the CLOA complex might be a novel therapeutic molecule that could ameliorate neuronal cell damage in PD.

Molecular characterization of alpha subunit 1 of sodium pump (ATP1A1) gene in Camelus dromedarius: its differential tissue expression potentially interprets the role in osmoregulation.

BACKGROUND: Dromedary or one-humped camel (Camelus dromedarius) is distinctively acclimatized to survive the arid conditions of the desert environment. It has an excellent ability to compete dehydration with substantial tolerance for rapid dehydration. Therefore, it offers an excellent model for studying osmoregulation. Molecular characterization of Na+/K+ ATPase as a central regulator of electrolyte normohemostasis affords a better understanding of this mechanism in camel. Here is the first to resolve the full-length of alpha-1 subunit of sodium pump (ATP1A1) gene with its differential expression in dromedary tissues. RESULTS: The nucleotide sequence for the recovered full cDNA of ATP1A1was submitted to the GenBank (NCBI GenBank accession #MW628635) and bioinformatically analyzed. The cDNA sequence was of 3760 bp length with an open reading frame (ORF) of 3066 bp encoding a putative 1021 amino acids polypeptide with a molecular mass of 112696 Da. Blast search analysis revealed the shared high similarity of dromedary ATP1A1gene with other known ATP1A1genes in different species. The comparative analysis of its protein sequence confirmed the high identity with other mammalian ATP1A1 proteins. Further transcriptomic investigation for different organs was performed by real-time PCR to compare its level of expression among different organs. The results confirm a direct function between the ATP1A1 gene expression and the order of vital performance of these organs. The expression of ATP1A1 mRNA in the adrenal gland and brain was significantly higher than that in the other organs. The noticed down expression in camel kidney concomitant with overexpression in the adrenal cortex might interpret how dromedary expels access sodium without water loss with relative high ability to restrain mineralocorticoid-induced sodium retention on drinking salty water. CONCLUSION: The results reflect the importance of sodium pump in these organs. Na+/K+ ATPase in the adrenal gland and brain than other organs.

Camel and bovine milk lactoferrins activate insulin receptor and its related AKT and ERK1/2 pathways.

Lactoferrin (LF) is a milk protein that may be an interesting candidate for the antidiabetic properties of milk due to its well-documented bioactivity and implication in diabetes. Here, we investigated the functional action of LF purified from camel and bovine milk (cLF, bLF) on insulin receptors (IR) and their pharmacology and signaling in hepatocarcinoma (HepG2) and human embryonic kidney (HEK293) cells. For this, we examined IR activation by bioluminescence resonance energy transfer (BRET) technology and the phosphorylation of its key downstream signaling kinases by western blot. The purified cLF and bLF induced phosphorylation of IR, AKT, and ERK1/2 in HepG2 and HEK293 cells. The BRET assays in HEK293 cells confirm the pharmacological action of cLF and bLF on IR, with a possible allosteric mode of action. This reveals for the first time the bioactivity of LF toward IR function, indicating it as a potential bioactive protein behind the antidiabetic properties of camel milk.

Taurine and Camel Milk Modulate Neurobehavioral and Biochemical Changes in Aluminum Chloride-Induced Alzheimer's Disease in Rats.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease associated with deficiency in motor coordination, cognitive impairment, and excessive reactive oxygen species production in the brain. OBJECTIVE: The study evaluated effects of taurine and camel milk (CM) on neurobehavior, amyloid-beta peptide 1-42 (Aß) expression, acetylcholinesterase, and superoxide dismutase activities in aluminum chloride (AlCl3) model of Alzheimer's disease in rats. METHODS: Thirty-five female Wistar rats were divided into seven groups (n = 5): Normal saline (0.2 mL/kg body weight); AlCl3 (100 mg/kg) (AD); CM (33 mL/kg); Taurine (50 mg/kg); AlCl3 (100 mg/kg) + CM (33 mL/kg); AlCl3 (100 mg/kg) + Taurine (50 mg/kg); and AlCl3 (100 mg/kg) + CM (33 mL/kg) + Taurine (50 mg/kg). The administration lasted for eight weeks via oral gavage. After the eighth week, neurobehavior assessments were performed. Rats were sacrificed, and brain and blood samples collected for analysis. RESULTS: There was a significant (p < 0.0001) increase in the duration of motor endurance in AD + CM rats, compared to AD rats. Duration of forced swimming time was lowest (p < 0.0001) in AlCl3 + Taurine rats, compared to that of AD rats. Concentration of Aß peptide decreased (p < 0.05) in AD rats, treated with CM and/or combination. In taurine-treated rats, superoxide dismutase activity was significantly (p < 0.05) higher than in AD rats. Treatment with taurine + CM increased (p < 0.05) acetylcholinesterase activity compared to controls. CONCLUSION: Taurine and CM enhanced cognition and sensorimotor activity by decreasing Aß peptide concentration and increasing superoxide dismutase and acetylcholinesterase activities in AD rats.