Mesenchymal stem cell therapy using Pal-KTTKS-enriched carboxylated cellulose improves burn wound in rat model.

Despite the great progress in developing wound dressings, delayed wound closure still remains a global challenge. Thus, developing novel wound dressings and employing advanced strategies, including tissue engineering, are urgently desired. The carboxylated cellulose was developed through the in situ synthesis method and further reinforced by incorporating pal-KTTKS to stimulate collagen synthesis and improve wound healing. The developed composites supported cell adhesion and proliferation and showed good biocompatibility. To boost wound-healing performance, adipose-derived mesenchymal stem cells (MSC) were seeded on the pal-KTTKS-enriched composites to be implanted in a rat model of burn wound healing. Healthy male rats were randomly divided into four groups and wound-healing performance of Vaseline gauze (control), carboxylated cellulose (CBC), pal-KTTKS-enriched CBC (KTTKS-CBC), and MSCs seeded on the KTTKS-CBC composites (MSC-KTTKS-CBC) were evaluated on days 3, 7, and 14 post-implantation. In each group, the designed therapeutic dressings were renewed every 5 days to increase wound-healing performance. We found that KTTKS-CBC and MSC-KTTKS-CBC composites exhibited significantly better wound healing capability, as evidenced by significantly alleviated inflammation, increased collagen deposition, improved angiogenesis, and considerably accelerated wound closure. Nevertheless, the best wound-healing performance was observed in the MSC-KTTKS-CBC groups among all four groups. This research suggests that the MSC-KTTKS-CBC composite offers a great deal of promise as a wound dressing to enhance wound regeneration and expedite wound closure in the clinic.

Pathogenesis of Common Ocular Diseases: Emerging Trends in Extracellular Matrix Remodeling.

The prevalence of visual impairments in human societies is worrying due to retinopathy complications of several chronic diseases such as diabetes, cardiovascular diseases, and many more that are on the rise worldwide. Since the proper function of this organ plays a pivotal role in people's quality of life, identifying factors affecting the development/exacerbation of ocular diseases is of particular interest among ophthalmology researchers. The extracellular matrix (ECM) is a reticular, three-dimensional (3D) structure that determines the shape and dimensions of tissues in the body. The ECM remodeling/hemostasis is a critical process in both physiological and pathological conditions. It consists of ECM deposition, degradation, and decrease/increase in the ECM components. However, disregulation of this process and an imbalance between the synthesis and degradation of ECM components are associated with many pathological situations, including ocular disorders. Despite the impact of ECM alterations on the development of ocular diseases, there is not much research conducted in this regard. Therefore, a better understanding in this regard, can pave the way toward discovering plausible strategies to either prevent or treat eye disorders. In this review, we will discuss the importance of ECM changes as a sentimental factor in various ocular diseases based on the research done up to now.

The role of oxygen tension in cell fate and regenerative medicine: implications of hypoxia/hyperoxia and free radicals.

Oxygen pressure plays an integral role in regulating various aspects of cellular biology. Cell metabolism, proliferation, morphology, senescence, metastasis, and angiogenesis are some instances that are affected by different tensions of oxygen. Hyperoxia or high oxygen concentration, enforces the production of reactive oxygen species (ROS) that disturbs physiological homeostasis, and consequently, in the absence of antioxidants, cells and tissues are directed to an undesired fate. On the other side, hypoxia or low oxygen concentration, impacts cell metabolism and fate strongly through inducing changes in the expression level of specific genes. Thus, understanding the precise mechanism and the extent of the implication of oxygen tension and ROS in biological events is crucial to maintaining the desired cell and tissue function for application in regenerative medicine strategies. Herein, a comprehensive literature review has been performed to find out the impacts of oxygen tensions on the various behaviors of cells or tissues.

Report of a phase 1 clinical trial for safety assessment of human placental mesenchymal stem cells therapy in patients with critical limb ischemia (CLI).

BACKGROUND: Critical limb ischemia (CLI) is associated with increased risk of tissue loss, leading to significant morbidity and mortality. Therapeutic angiogenesis using cell-based treatments, notably mesenchymal stem cells (MSCs), is essential for enhancing blood flow to ischemic areas in subjects suffering from CLI. The objective of this study was to evaluate the feasibility of using placenta-derived mesenchymal stem cells (P-MSCs) in patients with CLI. METHODS: This phase I dose-escalation study investigated P-MSCs in nine CLI patients who were enrolled into each of the two dosage groups (20 × 106 and 60 × 106 cells), delivered intramuscularly twice, two months apart. The incidence of treatment-related adverse events was the primary endpoint. The decrease in inflammatory cytokines, improvement in the ankle-brachial pressure index (ABI), maximum walking distance, vascular collateralization, alleviation of rest pain, healing of ulceration, and avoidance of major amputation in the target leg were the efficacy outcomes. RESULTS: All dosages of P-MSCs, including the highest tested dose of 60 × 106 cells, were well tolerated. During the 6-month follow-up period, there was a statistically significant decrease in IL-1 and IFN-γ serum levels following P-MSC treatment. The blood lymphocyte profile of participants with CLI did not significantly differ, suggesting that the injection of allogeneic cells did not cause T-cell proliferation in vivo. We found clinically substantial improvement in rest pain, ulcer healing, and maximum walking distance after P-MSC implantation. In patients with CLI, we performed minor amputations rather than major amputations. Angiography was unable to demonstrate new small vessels formation significantly. CONCLUSION: The observations from this phase I clinical study indicate that intramuscular administration of P-MSCs is considered safe and well tolerated and may dramatically improve physical performance and minimize inflammatory conditions in patients with CLI. TRIAL REGISTRATION: IRCT, IRCT20210221050446N1. Registered May 09, 2021.

Serum total carbohydrates, conjugated carbohydrates and total protein glycation index in diabetes mellitus.

BACKGROUND: Diabetes mellitus is defined according to fasting blood glucose and clinical signs. But, the markers of glycation have been used recently as a criterion to diagnose and monitor the therapy. OBJECTIVES: To measure serum total- and conjugated- saccharides and to define the new marker as serum total protein glycation index (sTPGI ) for diabetes. DESIGN AND METHODS: The study population consisted of 172 subjects who were divided to control and diabetic cases. Serum total and conjugated saccharides were measured and sTPGI was defined to discriminate serum glycosylated and glycated saccharides. RESULTS: Patients with diabetes compared with the controls had increased levels of serum (free) glucose, HbA1c, serum total carbohydrates, total conjugated carbohydrates and sTPGI. All three indices of serum carbohydrates showed significant positive correlation with serum glucose, HbA1c and diabetes. The equations: sTPGI = 0.12 Glucose (mg/dL) + 12 and sTPGI = 3.5HbA1c (%) + 5, were deduced for the association of sTPGI with serum free glucose and HbA1c. In ROC analysis, both HbA1c (AUC = 0.965, p ≤ 0.001) and sTPGI (AUC = 0.734, p ≤ 0.001) had strong and significant efficiency to discriminate diabetic cases from control subjects. CONCLUSIONS: The results confirm that sTPGI obtained by indirect assay has high significant efficiency comparable to HbA1c to diagnose diabetes. sTPGI relative to HbA1c indicates the mean level of glycaemia over a shorter period of about one month so it responds more quickly to changes in therapy.

Is obesity-induced ECM remodeling a prelude to the development of various diseases?

Due to the increasing incidence rate of obesity worldwide and the associated complications such as type 2 diabetes and cardiovascular diseases, research on the adipose tissue physiology and the role of the extracellular matrix (ECM) has gained tremendous attention. The ECM, one of the most crucial components in body tissues, undergoes remodeling and regeneration of its constituents to guarantee normal tissue function. There is a crosstalk between fat tissue and various body organs, including but not limited to the liver, heart, kidney, skeletal muscle, and so forth. These organs respond to fat tissue signals through changes in ECM, function, and their secretory products. Obesity can cause ECM remodeling, inflammation, fibrosis, insulin resistance, and disrupted metabolism in different organs. However, the mechanisms underlying the reciprocal communication between various organs during obesity are still not fully elucidated. Gaining a profound knowledge of ECM alterations during the progression of obesity will pave the way toward developing potential strategies to either circumvent pathological conditions or open an avenue to treat complications associated with obesity.

Histamine H1- and H2-receptors participate to provide metabolic energy differently.

Histamine participates in a variety of physiological functions. The local effects of histamine have a role to provide metabolic energy for the tissues. The objective of this work is to study the mechanism whereby histamine affects serum glucose and liver glycogen fractions. Six groups of 10 male rats received two injections with histamine, H1-agonist (dipyridylethylamine), H2-agonist (dimaprit), H1-agonist plus H1-antagonist (cetirizine), or H2-agonist plus H2-antagonist (famotidine). Serum glucose and liver glycogen fractions were measured. Histamine caused a significant increase in serum glucose (163.7 ± 5.4 vs. 153.2 ± 3.3 mg/dl, p = 0.023). The effect of histamine was mimicked by selective H1-agonist (164.2 ± 3.5 vs. 152.8 ± 2.9 mg/dl, p = 0.005) but not with H2-agonist (159.3 ± 3.7 vs. 156.3 ± 4.8 mg/dl, p = 0.281). The effect of H1-agonist was abolished in the presence of selective H1-antagonist. Treatment by H1- but not H2-agonist decreased total glycogen by about 35% (30.6 ± 0.5 vs. 47.3 ± 2.8 mg/g wet weight of liver, p = 0.003). The decrease happened wholly in ASG fraction (26.8 ± 1.2 vs. 43.7 ± 3.2 mg/g wet weight of liver, p = 0.004), while AIG did not change significantly (4.2 ± 0.5 vs. 4.5 ± 0.4 mg/g wet weight of liver, p = 0.724). Histamine causes to decrease glycogen in the liver and increased serum glucose. The effects of histamine were mediated via H1-receptors. ASG was metabolically active fraction of liver glycogen in this process. The results confirm the role of histamine in providing metabolic energy of the tissues.

Hypolipemic effects of histamine is due to inhibition of VLDL secretion from the liver: involvement of both H1 and H2-receptors.

The research was performed to study the mechanism whereby histamine affects the profile of plasma lipids. Six groups of ten male rats were received two injections with histamine or its H1- and H2-agonists and antagonists. Histamine caused a significant decrease in the concentrations of triglyceride, total cholesterol, and LDLc, while HDLc had no significant change. The rate of VLDL secretion was 263.6 ± 25.8 mg/h dL in control rats and was inhibited by about 68% in histamine injected rats. These changes have been mimicked by either histamine H1- or H2-agonists. The effects of H1- and H2-agonists were abolished in the presence of cetirizine and famotidine respectively. Histamine causes a significant decrease in serum triglyceride, total, and LDL-cholesterol by both H1 and H2-receptors. The decrease in serum lipids is due to the inhibitory effect of histamine or its agonists on VLDL secretion from the liver.

Therapeutic and Protective Potential of Mesenchymal Stem Cells, Pharmaceutical Agents and Current Vaccines Against COVID-19.

It has been almost 18 months since the first outbreak of COVID-19 disease was reported in Wuhan, China. This unexpected devastating phenomenon, raised a great deal of concerns and anxiety among people around the world and imposed a huge economic burden on the nations' health care systems. Accordingly, clinical scientists, pharmacologists and physicians worldwide felt an urgent demand for a safe, effective therapeutic agent, treatment strategy or vaccine in order to prevent or cure the recently-emerged disease. Initially, due to the lack of specific pharmacological agents and approved vaccines to combat the COVID-19, the disease control in the confirmed cases was limited to supportive care. Accordingly, repositioning or repurposing current drugs and examining their possible therapeutic efficacy received a great deal of attention. Despite revealing promising results in some clinical trials, the overall results are conflicting. For this reason, there is an urgent need to seek and investigate other potential therapeutics. Mesenchymal stem cells (MSC), representing immunomodulatory and regenerative capacity to treat both curable and intractable diseases, have been investigated in COVID-19 clinical trials carried out in different parts of the world. Nevertheless, up to now, none of the MSC-based approaches has been approved in controlling COVID-19 infection. Thanks to the fact that the final solution for defeating the pandemic is developing a safe, effective vaccine, enormous efforts and clinical research have been carried out. In this review, we will concisely discuss the safety and efficacy of the most relevant pharmacological agents, MSC-based approaches and candidate vaccines for treating and preventing COVID-19 infection.

Advanced approaches to regenerate spinal cord injury: The development of cell and tissue engineering therapy and combinational treatments.

Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians' clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.

The interplay between extracellular matrix and progenitor/stem cells during wound healing: Opportunities and future directions.

Skin wound healing, a dynamic physiological process, progresses through coordinated overlapping phases to restore skin integrity. In some pathological conditions such as diabetes, wounds become chronic and hard-to-heal resulting in substantial morbidity and healthcare costs. Despite much advancement in understanding mechanisms of wound healing, chronic and intractable wounds are still a considerable challenge to nations' health care systems. Extracellular matrix (ECM) components play pivotal roles in all phases of wound healing. Therefore, a better understanding of their roles during wound healing can help improve wound care approaches. The ECM provides a 3D structure and forms the stem cell niche to support stem cell adhesion and survival and to regulate stem cell behavior and fate. Also, this dynamic structure reserves growth factors, regulates their bioavailability and provides biological signals. In various diseases, the composition and stiffness of the ECM is altered, which as a result, disrupts bidirectional cell-ECM interactions and tissue regeneration. Hence, due to the impact of ECM changes on stem cell fate during wound healing and the possibility of exploring new strategies to treat chronic wounds through manipulation of these interactions, in this review, we will discuss the importance/impact of ECM in the regulation of stem cell function and behavior to find ideal wound repair and regeneration strategies. We will also shed light on the necessity of using ECM in future wound therapy and highlight the potential roles of various biomimetic and ECM-based scaffolds as functional ECM preparations to mimic the native stem cell niche.

Fixed-time and continuous assays of very-low-density lipoprotein secretion rate from rat liver: mean vs. instantaneous velocity.

AIM OF THE STUDY: The secretion rate of triglyceride from rat liver is assayed by the measurement of triglyceride accumulation in plasma when its clearance is inhibited. The aim of the study was to measure and compare the secretion rate of triglyceride from rat liver by two methods of fixed-time and continuous assays. MATERIAL AND METHODS: A single dose of 200 mg of poloxamer-407 (P-407) was injected i.p. into starved male rats. The secretion rate of triglyceride was measured by fixed-time and continuous assays. RESULTS: The time course for the changes of serum triglyceride following injection of P-407 showed three distinct phases: a lag period of about 30 minutes, a linear increase in serum triglyceride that lasted more than 4 hours, and a slight decline of triglyceride accumulation that lasted about 24 hours. The mean rate of triglyceride secretion was 234.1 ±9.6 mg/dl/h during the linear phase. The linear phase was divided into five time protocols of 240, 180, 120, 60, and 30 minutes and the secretion rate was measured at three points of time in each protocol. The mean rate of triglyceride secretion was 3.91 ±0.15, 3.83 ±0.16, 3.76 ±0.29, 3.57 ±0.43 and 3.13 ±0.34 mg/dl/min in these protocols respectively. In the kinetic assay, the change in the absorbance per three successive five minutes (ΔA/Δt) was measured and the secretion rate was calculated as 3.82 ±0.11 mg/dl/min. CONCLUSIONS: The rate of triglyceride secretion can be measured by both fixed-time and kinetic assays and was about 3.82 ±0.11 mg/dl/min. The results of the two methods are more corresponded as the mean and instantaneous velocity respectively.

Iron hypothesis and coronary artery disease in geriatric patients.

Context and aims: Iron is a pro-oxidant factor in the pathogenesis of CAD. The association of body iron status was investigated relative to the occurrence and severity of CAD.Design and methods: The subjects consisted of 110 males and 115 females who were classified as either a CAD case or a control according to the results of coronary angiography.Results: A new parameter, the "serum free iron index," was defined as the ratio of serum iron to UIBC. The level of ferritin showed significant increase [97.2 (67.0-171.2) µg/L vs. 85.6 (52.5-129.4), p = .034], whereas serum total iron, free iron index, transferrin, UIBC and iron saturation were unchanged in CAD patients relative to control group. Among the indices of body iron only serum ferritin had significant association with the likelihood (OR of 1.004 (1.000-1.007), p = .04) and severity of CAD [χ2(3)= 7.99, p = .01], but the correlation was lessened in the presence of classical risk factors. Serum ferritin had also the highest and significant efficiency to predict CAD (AUC = 0.61, p = .020).Conclusions: Serum ferritin as a marker of intracellular iron has significant association with CAD; nevertheless, the correlation is not independent. Since iron deficiency is prevalent in elderly patients, iron hypothesis needs to expand to the both sides of iron deficiency and toxicity.

Serum Creatinine and Occurrence and Severity of Coronary Artery Disease.

INTRODUCTION: The risk for cardiovascular disease is increased in all stages of the impairment of renal function. It is proposed that serum creatinine is a marker of diabetes and coronary artery disease (CAD) as well as the kidney function. AIM: to study the association of serum creatinine with the likelihood and severity of CAD. The study population consisted of 262 males and 266 females who were classified as CAD cases and controls according to the results of coronary angiography. RESULTS: Patients with CAD compared with the controls had increased levels of serum urea and creatinine. Serum creatinine showed significant positive correlation with male sex, hypertension and negative correlation with total- and HDL-cholesterol and apoAI. Serum urea, uric acid and potassium were the major determinants of creatinine. All hematological parameters were strong negative correlates of creatinine. None of markers of inflammation had significant correlation with creatinine. Creatinine was associated significantly with the prevalence [odds ratio of 1.79 (1.47-2.20), p<0.001] and severity of CAD [F(3,528)= 3.0, p=0.03]. Serum creatinine was excluded from the regression equation after adjustment for major risk factors. CONCLUSION: Serum creatinine has significant association with CAD, but the correlation is not independent. Creatinine have significant association with markers of kidney function and body water status, but not with markers of inflammation and insulin function.

Esterification of HDL-cholesterol is Decreased in Diabetes Mellitus and CAD and Enhanced Following Treatment with Statins.

BACKGROUND: The main goal of using statins is to reduce the level of plasma cholesterol, meanwhile they have a wide spectrum of actions. OBJECTIVES: To identify the effect of statins on fractional cholesterol esterification (FCE) as well as the complete profile of lipids and (apo)lipoproteins. DESIGN AND METHODS: In an age and sex matched case-control study, 400 subjects who were referred for coronary angiography were divided into two groups according using statins. RESULTS: Total cholesterol was decreased significantly following treatment with statins (165.6 ± 38.0 mg/dL vs. 205.3 ± 48.4, p£0.001). About 90% of the reduction was occurred in nonHDL and 10% in HDL fraction. Reduction of nonHDL cholesterol (125.2 ± 35.2 mg/dL vs. 162.8 ± 45.2, p£0.001) occurred on both unesterified (52.4 ± 21.5 mg/dL vs. 65.2 ± 25.5, p£0.001) and esterified cholesterol (74.7 ± 27.3 mg/dL vs. 96.6 ± 34.1, p£0.001). But the decrease in HDL cholesterol (40.4 ± 10.0 mg/dL vs. 42.3 ± 9.9, p£0.079) happened exclusively in unesterified fraction (10.9 ± 3.4 vs. 15.2 ± 5.1, p£0.001) and was counterbalanced with a significant increase in esterified portion (29.5 ± 8.2 mg/dL vs. 27.2 ± 9.5, p£0.020). The ratio of esterified- per total- cholesterol in HDL was 67.5 ± 8.1% in the control group and was decreased to 58.0 ± 14.9% (p£0.01) in diabetes and CAD and increased to 73.5 ± 6.9 (p£0.01) after using statins. CONCLUSIONS: The results suggest that the percent of esterified cholesterol in HDL fraction is decreased in diabetes and CAD patients and increased by using statins.

Stem cell therapy for lung diseases: From fundamental aspects to clinical applications.

The respiratory system is a complex group of organs in the human body, all of which are necessary in breathing. Due to its special anatomy and composition, after exposure to various damaging factors such as micro particles, carbon granules and toxic gases, the respiratory system can be affected by a variety of damage without return to its original state. Currently, the prevalence of lung diseases, including asthma, and chronic obstructive pulmonary diseases, such as emphysema, has increased remarkably. New therapeutic approaches are desperately needed to discover regenerative medicine approaches, especially cell therapy. This review summarizes the recent advances in stem cell treatments and the research efforts conducted through the application of stem cell therapy for respiratory system diseases. In particular, researchers have used animal models to gather data about treating lung injury by stem cell transplantation. This review concentrated on the findings about route, timing and adjustment of cell transplantation dose, optimum stem cell type selection and potency marker of cells as therapeutic agents. These factors are essential subjects for approval and clinical transplantation. The current clinical trials aiming at treatment of lung diseases by stem cells are mentioned and discussed.

The Ratio of Unesterified/esterified Cholesterol is the Major Determinant of Atherogenicity of Lipoprotein Fractions.

BACKGROUND: The hypothesis is proposed that the atherogenicity of lipoporotein fractions is correlated with the content of unesterified cholesterol. OBJECTIVES: To evaluate the role and prognostic values of unesterified and esterified cholesterol in lipoprotein fractions for coronary artery disease (CAD). DESIGN AND METHODS: The study population consisted of 400 patients who were divided to CAD controls and cases according to the data of coronary angiography. Fractional cholesterol esterification (FCE) as well as the complete profile of lipids and (apo)lipoproteins were determined. RESULTS: Total cholesterol was increased significantly in CAD patients (196.3 ± 52.3 mg/dL vs. 185.7 ± 48.0, p≤ 0.049) and the increment occurred totally in unesterified portion (77.2 ± 28.4 mg/dL vs. 71.1 ± 24.4, p≤ 0.031). HDL cholesterol showed a significant decrease in CAD group (39.9 ± 9.5 mg/dL vs. 44.6 ± 10.5, p≤ 0.001), but the decrement occurred wholly in the esterified portion (26.2 ± 9.2 mg/dL vs. 31.1 ± 8.1, p≤ 0.001). NonHDL cholesterol was increased significantly in CAD group (156.8 ± 48.3 mg/dL vs. 140.3 ± 43.6, p≤ 0.001), and the changes occurred in both un- and esterified portions. FCE in HDL was diminished significantly in CAD patients (64.8 ± 13.9% vs. 69.3 ± 7.9, p≤ 0.01). In multivariate logistic regression analysis, unesterified cholesterol in NonHDL (UeNonHDLc) and esterified cholesterol in HDL (EsHDLc) excluded total cholesterol and HDLc respectively from the regression equation. In ROC analysis, the ratio of UeNonHDLc/EsHDLc was the strongest predictor for CAD among cholesterol subfractions. CONCLUSIONS: The results confirm that UeNonHDLc is atherogenic and EsHDLc is antiatherogenic and are independent risk factors for CAD.

Carbenoxolone Could Deteriorate Streptozotocin-induced Diabetes through Induction of Heat Shock Protein 70 and IFN-γ in C57BL/6 Mice.

Type 1 diabetes (T1D), a spontaneous autoimmune disease, is associated with destruction of insulin-producing ß-cells in the pancreas. Since some heat shock proteins (HSP), such as HSP70 exert a protective effect in both tissues and cells, the present study was conducted to elucidate the effects of carbenoxolone (CBX) as an HSP70 inducer on T1D. The disease was induced in male C57BL/6 mice using streptozotocin (STZ) and subjects were allocated to therapeutic 1 and therapeutic 2 groups, as well as negative and positive control groups. The treated mice (therapeutic 1 and therapeutic 2 groups) received 50 mg/kg CBX intraperitoneally every 24 hours, in the therapeutic 1  group the drug was injected before and after disease induction whereas in the therapeutic 2 group the drug was injected only after disease induction. Serum fasting blood sugar (FBS) level, cytokines production (Interferon-gamma (IFN-γ), Interleukin 10 (IL-10), and IL-17), serum HSP70 level and CD4+CD25+Foxp3+ regulatory T cell (Treg) frequency measurements were outperformed 14 days after the last STZ injection. Our results showed that in the treated groups, serum HSP70, IFN-γ, and IL-17 levels were increased in contrast to the untreated groups. The IL-10 level was markedly decreased in comparison to untreated diabetic mice (p<0.05). Moreover, it was found that the frequency of Tregs in treated mice was lower in comparison to the untreated mice but the difference was not significant (p>0.05). Our results confirm that CBX might through HSP70 induction, followed by increasing IFN-γ level leads to suppression of IL-10 production in diabetic mice resulted in toxic effects on pancreatic islet beta cells and deteriorating of disease.

Physicochemical Characteristics of Rat Muscle Glycogen Fractions.

INTRODUCTION: Homogenization of animal tissues with cold Perchloric Acid (PCA) produces two fractions of glycogen, Acid Soluble Glycogen (ASG) and Acid Insoluble Glycogen (AIG). AIM: To determine some physicochemical characteristics of muscle glycogen fractions in two groups of rat. MATERIALS AND METHODS: An experimental study was conducted on two groups of five male rats. Rats in control group were kept at rest and in case group on 30 minutes physical activity. The content of carbohydrate, protein, phosphate, index and relative Molecular Weights (MWs) were determined for glycogen fractions. RESULTS: Total glycogen decreased following muscular activity (1.40±0.08, mg/g wet muscle vs. 0.97±0.11, p<0.05) and the change occurred totally in ASG (1.02±0.07 vs. 0.57±0.07, p=0.017), whereas, AIG changed insignificantly (0.39±0.05 vs. 0.36±0.02, p=0.5). The protein content of AIG was about 5.5 times of ASG fraction. The ratio of carbohydrate to protein was 0.33±0.01 (mg/mg) in ASG and decreased to 0.19±0.02, p=0.01 after 30 minute activity. This ratio in AIG was about 6% of ASG fraction and did not change significantly during physical activity. The ratio of phosphate to protein was three times in ASG relative to AIG at rest and did not change following activity. The index of molecular weight was calculated for each fraction of glycogen as the ratio of concentration per osmolality (mg/mmol). The index was 1.82±0.02 for ASG at rest and decreased significantly to 1.07±0.12, p<0.05 following 30 minutes activity. The index did not change significantly for AIG fraction (0.56±0.05 vs. 0.48±0.10, p=0.4). The relative MW of the fractions of ASG to AIG was 3.3±0.3 at rest and decreased significantly to 2.2±0.6, p<0.05 following 30 minutes activity. CONCLUSION: Two fractions of muscle glycogen, ASG and AIG, differ in the relative carbohydrate: protein content and ASG have a higher mean of MW and is more metabolic active form.