ß-lapachone protects against doxorubicin-induced hepatotoxicity through modulation of NAD+ /SIRT-1/FXR/p-AMPK/NF-kB and Nrf2 signaling axis.

Doxorubicin (DOX) is a widely used antineoplastic drug, but its clinical use is limited by significant toxicities, such as hepatotoxicity. In this study, we evaluated the effects of ß-lapachone (ß-LAP), a natural quinone-containing compound, in a mouse model of DOX-induced hepatotoxicity. ß-LAP was orally administered at 1.25, 2.5, and 5 mg/kg for 4 days, and a single dose of DOX (20 mg/kg) was injected intraperitoneally on the second day. Histopathological changes, liver function markers, antioxidant and inflammatory markers were assessed. ß-LAP ameliorated liver injury and liver function markers evoked by DOX. ß-LAP also downregulated the mRNA expression of nuclear factor-kB-corresponding genes including interleukin-6, interleukin-1ß, and tumor necrosis factor-α. Moreover, ß-LAP increased the nuclear factor erythroid 2-related factor 2 target genes heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1, along with antioxidant enzymes including reduced glutathione, catalase, and superoxide dismutase with simultaneous reduction in the lipid peroxidation product malondialdehyde. Meanwhile, it recovered NAD+ /NADH ratios and subsequently elevated the protein levels of sirtuin-1 (SIRT-1), farnesoid X receptor (FXR), and phosphorylated AMP-activated protein kinase (p-AMPK). Collectively, these findings suggest a protective role of ß-LAP against DOX-induced hepatotoxicity by partly regulating the NAD+ /SIRT-1/FXR/p-AMPK axis.

The effect of calorie-restriction along with thylakoid membranes of spinach on the gut-brain Axis Pathway and oxidative stress biomarkers in obese women with polycystic ovary syndrome: a Randomized, Double-blind, placebo-controlled clinical trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have higher intestinal mucosal permeability, leading to the lipopolysaccharide (LPS) leakage and endotoxemia. This, in turn, leads to oxidative stress (OS) and neuro-inflammation caused by the gut-brain axis, affecting the neurotrophic factors levels such as brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100 B) levels. In this study, it was hypothesized that the thylakoid membranes of spinach supplementation along with a hypocaloric diet may have improved the LPS levels, neurotrophic factors, and OS in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled, and clinical trial, 48 women with obesity and diagnosed with PCOS based on Rotterdam criteria were randomly assigned to thylakoid (N = 21) and placebo groups (N = 23). A personalized hypocaloric diet with 500 calories less than the total energy expenditure was prescribed to all patients. The participants were daily supplemented with either a 5 g/day thylakoid-rich spinach extract or a placebo (5 g cornstarch) for 12 weeks along with a prescribed low-calorie diet. Anthropometric measurements and biochemical parameters were assessed at baseline and after the 12-week intervention. RESULTS: A statistically significant decrease in the LPS levels (P < 0.001) and an increase in the BDNF levels (P < 0.001) were recorded for the participants receiving the oral thylakoid supplements and a low-calorie diet. Furthermore, significant decreases were observed in fasting blood glucose, insulin, homeostatic model of assessment for insulin resistance, free testosterone index, and follicle-stimulating hormone / luteinizing hormone ratio in both groups (P < 0.05). No significant differences were detected between the two groups regarding the changes in malondialdehyde, catalase, total antioxidant capacity, and S100B levels (P > 0.05). CONCLUSIONS: In sum, the thylakoid membranes of spinach supplemented with a hypocaloric diet reduced the LPS levels, increased the BDNF levels, and improved the glycemic profile and sex-hormone levels; however, they had no effects on the OS markers levels after 12 weeks of intervention.

Chronic Kombucha Beverage Consumption Attenuates Inflammatory Markers and Histopathology of Brain Tissue in Transnet Global Brain Ischemia in Rats.

There is evidence that kombucha beverage (KB), a traditional fermented beverage, has a preventive effect on experimental brain ischemia. According to our previous studies, pre-treatment of KB attenuates brain edema and improves motor skills and oxidative stress in a rat model of global brain ischemia. This study was designed to evaluate the effects of the pre-treatment of KB, as a novel agent, on pro-inflammatory parameters and brain histopathology changes following global brain ischemia. Adult male Wistar rats were randomly divided into the sham, the control, and the groups treated with kombucha (KB1 and KB2 groups). KB at doses 1 and 2 mL/kg was prescribed two-week consecutive days before induction of global brain ischemia. Global brain ischemia was induced by blocking common carotid arteries for 60 min and the following reperfusion by 24 h. The serum and brain levels of tumor necrosis factor-α(TNF-α), IL-1ß, histopathological change, and infarct volume are determined using the ELISA, hematoxylin and eosin (H&E), and 2,3,5-triphenyl tetrazolium chloride (TTC) staining, respectively. This study indicated that pre-treatment of KB significantly reduced infarct volume, the serum, and brain levels of TNF-α and IL-1ß. The histopathological finding of the brain tissue confirmed a protective role for pre-treatment KB in the ischemic rats. Thus, the present study showed that the beneficial effects of KB pre-treatment on brain ischemic may be mediated by decreasing pro-inflammatory parameters.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Hematotoxicity induced by simultaneous exposure to noise and toluene in New Zealand white rabbits: Synergistic and antagonistic effects.

Exposure to numerous pollutants is prevalent in workplaces. Examination of combined exposure to different harmful physical factors and chemicals has offered new insights into toxicology in recent years. This study aimed to investigate the hematological alterations caused by exposure to noise and toluene. Twenty-four New Zealand white rabbits were exposed to 1000 ± 50 ppm toluene and/or 100 ± 5 dB noise for 14 consecutive days. Exposure to noise and toluene changed a number of parameters of white blood cells (WBC), red blood cells (RBC), and platelets on different days after the exposure. Simultaneous exposure to noise and toluene increased WBC, and exposure to noise and toluene alone decreased RBC. Exposure to noise and toluene alone increased basophile, monocyte, and neutrophil counts. The coefficient of variation of red blood cell distribution width (RDW-CV) and the standard deviation of red blood cell distribution width (RDW-SD) significantly increased after co-exposure to noise and toluene. Platelet levels increased in the noise-exposed and the co-exposed groups and decreased in the toluene-exposed group. Furthermore, co-exposure to noise and toluene induced dissimilar synergistic and antagonistic effects on the hematological indices. According to the results of this study, simultaneous exposure to toluene and noise can aggravate some hematotoxic effects compared to exposure to noise or toluene alone. The results also demonstrated the vital role of the modulatory mechanisms of the body in controlling the detrimental effects of stressors.

Association Between Sex Hormone-Binding Globulin, Atherogenic Indices of Plasma Among Young Sedentary Males.

Background: Males are more likely than females to suffer from cardiovascular disease (CVD). So, sex hormones may modify these variations and affect the lipid profile. We examined the relationship between sex hormone-binding globulin (SHBG) and CVD risk factors among young males in this study. Methods: Using a cross-sectional design, we measured total testosterone, SHBG, lipids, glucose, insulin, antioxidant parameters, and anthropometric factors in 48 young males in the age range of 18 to 40 years. Atherogenic indices of plasma were calculated. In this study, a partial correlation analysis was carried out to assess the relationship between SHBG and other variables after adjustment for confounders. Results: According to the results of multivariable analyses adjusted for age and energy, SHBG had a negative correlation with total cholesterol (r = -.454, P =.010), low-density lipoprotein cholesterol (r = -.496, P =.005), quantitative insulin-sensitivity check index, and positive correlation with high-density lipoprotein cholesterol (r = .463, P =.009). No significant correlation was observed between SHBG and triglycerides (P >.05). Several atherogenic indices of plasma have a negative correlation with SHBG levels. These include Atherogenic Index of Plasma (r = -.474, P = .006), Castelli Risk Index (CRI)1 (r = -.581, P < .001), CRI2 (r = -.564, P = .001), and Atherogenic Coefficient (r = -.581, P < .001). Conclusion: Among young men, high plasma SHBG was associated with reduced CVD risk factors, modified lipid profile and atherogenic ratios, and better glycemic markers. Therefore, reduced SHBG concentrations could be a prognostic marker of CVD among young sedentary males.

Vitamin D supplementation and cardiac tissue inflammation in obese rats.

OBJECTIVE: The current study was aimed to evaluate the effects of active form of vitamin D on TGF- ß, NF-κB and MCP-1 in heart tissue of obese rats. METHODS: Forty rats were allocated into groups of normal diet and high fat diet for sixteen weeks; then each group was divided into two groups that received either 500 IU/kg vitamin D or placebo for five weeks. Biochemical parameters were assessed by ELISA kits. RESULTS: Vitamin D reduced TGF-ß in obese rats supplemented with vitamin D compared with other groups (P = 0.03). Moreover, vitamin D reduced MCP-1 concentrations in the heart tissues of both vitamin D administered groups compared to placebo one (P = 0.002). NF-κB in the heart of HFD + vitamin D group was significantly lower (P = 0.03). Current study also showed that vitamin D improves glycemic status and reduce insulin resistance significantly in HFD group (P = 0.008). CONCLUSION: Vitamin D was a potential anti- inflammatory mediator of cardiovascular disease and markers of glycemic status in obese rats. Further investigations are needed to better identify the therapeutic role of this vitamin in CVD and to elucidate the underlying mechanisms.

Effects of hemp seed alone and combined with aerobic exercise on metabolic parameters, oxidative stress, and neurotrophic factors in young sedentary men.

Hemp seed and physical activity (PA) have many benefits for the metabolic and brain health of the body. This study investigated the effects of hemp seed alone and aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men. This double-blind, placebo-controlled, randomized clinical trial was conducted on 48 sedentary young men in Tabriz, Iran, from April to August. The researcher in this study randomized all participants into four groups, including (1) hemp seed, (2) hemp seed + PA, (3) PA + placebo, and (4) placebo. Hemp seed supplement was administered in two 1-g capsules daily, and aerobic PA was performed a week thrice. Levels of anthropometric indices, dietary intake, antioxidant markers, lipid profile, fasting blood sugar (FBS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), balance, reaction time, and sit-ups were evaluated for all participants at baseline and post-intervention. We used ANOVA and ANCOVA analysis to compare oxidative stress and neurotropic factors in all intervention groups. If the distribution of the response variable was not normal, the non-parametric equivalent of these tests was used (Wilcoxon and Kruskal-Wallis tests). We performed all statistical analyzes using SPSS software version 23, and the significance level was considered 0.05 in all the statistical tests. Aerobic PA with hemp seed consumption caused a significant difference in weight, body mass index, fat mass, high-density lipoprotein, catalase, and BDNF compared with baseline. Also, aerobic PA alone caused significant changes in body weight, fat mass, and triglyceride compared with baseline. Consumption of hemp seeds alone caused a significant increase in high-density lipoprotein levels compared with baseline. At the end of the study, fat mass, total cholesterol, low-density lipoproteins, and BDNF were significantly different between the groups. According to our results, aerobic PA combined with hemp seed consumption may improve anthropometric indices, lipid profile, and BDNF and improve health outcomes like cardiovascular comorbidities, oxidative stress, and insulin resistance. PRACTICAL APPLICATIONS: A sedentary lifestyle has numerous health-threatening consequences like cardiovascular comorbidities, oxidative stress, and insulin resistance. The importance of physical activity (PA) in improving these clinical manifestations is well-known; however, the potential benefits of herbal therapy combined with PA in reducing the side effects of a sedentary lifestyle have not been well studied. In the current research, we evaluated the benefits of hemp seed alone and combined with aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men for the first time. According to our results, aerobic PA combined with hemp seed consumption improved anthropometric indices, lipid profile, and brain-derived neurotrophic factor among young sedentary men.

Intra-ovarian injection of bone marrow-derived c-Kit+ cells for ovarian rejuvenation in menopausal rats.

Introduction: Cell-based therapies with certain cell types are touted as novel and hopeful therapeutic intervention in the clinical setting. Here, we aimed to assess the regenerative potential of c-Kit+ cells in the rejuvenation of ovarian tissue and fertility rate in rat model of premature ovarian failure (POF). Methods: Rats were treated with 160 mg/kg/BW of 4-vinylcyclohexene dioxide for 15 days. Freshly enriched rat bone marrow-derived c-Kit+ (MACS) and c-Kit- cells (4×105 cells/10 µL) were transplanted into the ovaries of treatment and control animals. Prior to transplantation as well as 2, 4, 6, and 8 weeks post-transplantation, randomly-selected rats were euthanized and ovarian tissues were subjected to pathophysiological examinations and real-time PCR analyses. Results: POF status was confirmed by the presence of pathological features and a decreased number of immature and mature follicles compared with the control group (P < 0.05). Histological examination revealed a substantial reduction of atretic follicles in POF rats receiving c-Kit+ cells in comparison with POF rats that did not receive these cells (P < 0.05). Compared with the control samples, angiogenesis-related genes, Angpt2 and KDR, showed increased and decreased expressions in POF ovaries, respectively (P < 0.05). c-Kit+ cells had potential to restore angiogenesis in the ovarian tissue within normal ranges. Systemic levels of FSH did not significantly change in pre- or post-transplantation time points for any group (P > 0.05). Notable reduction of collagen deposition was found in c-Kit-treated rats. Transplantation of c-Kit+ cells also restored the reduced fertility rate (P < 0.05). Conclusion: The administration of c-Kit+ cells can modulate angiogenesis and pathological changes, leading to the rejuvenation of ovarian function of a rat model of premature menopause.

TGF-ß1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways.

Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-ß1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham, unilateral ureteral obstruction (UUO), UUO+galunisertib (150 and 300 mg/kg/day), galunisertib (300 mg/kg/day). The UUO markedly induced renal fibrosis and injury as indicated by renal functional loss, increased levels of collagen Iα1, fibronectin and α-SMA; it also activated both the Smad 2/3 and MAPKs pathways as indicated by increased levels of TGF-ß1, p-Smad 2, p-Smad 3, p-p38, p-JNK and p-ERK. These UUO-induced changes were markedly attenuated by oral administration of galunisertib, the TGFßRI small molecule inhibitor. In conclusion, we demonstrated that TGF-ß1 receptor blockade can prevent UUO-induced renal fibrosis through indirect modulation of Smad and MAPKs signaling pathways and may be useful as a therapeutic agent in treatment and/or prevention of renal fibrosis.

Effects of sulfur dioxide, ozone, and ambient air pollution on lung histopathology, oxidative-stress biomarkers, and apoptosis-related gene expressions in rats.

PURPOSE OF THE STUDY: Ambient air pollution (AAP) has become an important health problem globally. Besides, several pieces of evidence indicate that air pollutants such as sulfur dioxide (SO2) and ozone (O3) are major contributors to a wide range of non-communicable diseases. The present study investigated the effects of AAP, sulfur dioxide, and ozone on oxidative stress, histopathology, and some apoptosis-related genes expressions of lung tissue in a rat model. MATERIALS AND METHODS: Thirty-two Wistar rats were randomly divided into the control, AAP, sulfur dioxide (10 ppm), and ozone (0.6 ppm) groups. After five consecutive weeks' exposure to the selected pollutants (3 h/day), lung tissues were harvested and immediately fixed with formalin. The samples were routinely processed, sectioned, stained with hematoxylin and eosin (H&E), and finally assessed for presence of pathological changes. Expression changes of BAX, p-53, EGFR, caspase-3, caspase-8 and caspase-9 were assayed using the RT-qPCR method. One hundred milligrams of lung tissues were extracted and the supernatants were used for assaying malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase activities. RESULTS: GPx activity was increased in the ozone (P = 0.05) and AAP (P < 0.001) groups and also MDA level in sulfur dioxide group (P = 0.008). Pathological lesions were mild, moderate, and severe in the sulfur dioxide, ozone, and AAP groups, respectively, as compared to control group (P ˂ 0.05). Exposure to AAP and sulfur dioxide enhanced BAX (P = 0.002) and caspase-8 (P < 0.001) mRNA expression, respectively. Caspases-3 and -8 mRNA expressions were elevated in ozone group (P < 0.001). CONCLUSIONS: The results indicated induction of oxidative stress. Our results suggest the apoptosis stimuli effect of AAP and also the extrinsic apoptotic pathway trigger effect of sulfur dioxide and ozone in the lung tissue in the concentrations used in the present study. The histopathological and the genes expression changes may be a result of the induced oxidative stress in the lung tissues.

Toxicopathological changes induced by combined exposure to noise and toluene in New Zealand White rabbits.

Noise and toluene can have significant adverse effects on different systems in the human body, but little is known about their combination. The aim of this study was to see how their combined action reflects on serum levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß), body weight, and pathological changes in the heart, lung, stomach, and spleen tissues. To do that we exposed New Zealand rabbits to 1000 mg/L toluene and 100 dB of white noise in a chamber specifically designed for the purpose over two consecutive weeks. Serum levels of TNF-α and IL-1ß were measured with the enzyme-linked immunosorbent assay (ELISA), whereas Bax and Bcl-2 expressions in tissues were determined with real-time polymerase chain reaction (PCR). Noise and toluene changed TNF-α and IL-1ß serum levels on different days following the end of exposure and significantly increased the Bax/Bcl-2 ratio in the lung and spleen. In addition, they induced different pathological changes in the heart, lung, spleen, and stomach tissues. This study has confirmed that exposure to noise and toluene can induce a range of toxicopathological changes, probably by inducing inflammatory pathways and apoptosis, but their combined effects look weaker than those of its components, although histopathological findings suggest the opposite.

Protective effects of di- and tri-peptides containing proline, glycine, and leucine on liver enzymology and histopathology of diabetic mice.

CONTEXT: Small peptides as multifunctional biomolecules can prevent the metabolic disorders such as diabetes. OBJECTIVE: The purpose of this study was to investigate the effects of small peptides on the enzymes and histopathology of the liver in mice exposed to diabetes. METHODS: Di- and tri-peptides containing proline, glycine, and leucine were produced by solid phase peptide synthesis (SPPS) protocol. The effects of produced peptides as well as carnosine (Ala-His) and glutathione (Glu-Cys-Gly) were evaluated on hepatic enzymes activity by enzymatic method and histopathology of liver using hematoxylin and eosin and TUNEL staining to assess histologic changes and apoptosis in diabetes induced by multiple low doses of streptozotocin (MLDS). RESULTS: The Ala-His, Leu-Gly and Pro-Gly-Pro peptides had the higher protective effects against the effects of diabetes on the enzymes and histologic changes of liver in mice. CONCLUSION: These peptides can be raised as considerable pharmaceutical preventive agent against diabetes development.

A novel multifunctional bilayer scaffold based on chitosan nanofiber/alginate-gelatin methacrylate hydrogel for full-thickness wound healing.

Due to their lack of multifunctionality, the majority of traditional wound dressings do not support all the clinical requirements. Bilayer wound dressings with multifunctional properties can be attractive for effective skin regeneration. In the present study, we designed a multifunctional bilayer scaffold containing Chitosan-Polycaprolactone (PC) nanofiber and tannic acid (TA) reinforced methacrylate gelatin (GM)/alginate (Al) hydrogel (GM/Al/TA). PC nanofibers were coated with GM/Al/TA hydrogel to obtain a bilayer nanocomposite scaffold (Bi-TA). The GM/Al/TA hydrogel layer of Bi-TA showed antibacterial, free radical scavenging, and biocompatibility properties. Also, PC nanofiber acted as a barrier for preventing bacterial invasion and moisture loss of the hydrogel layer. The wound healing performance of the Bi-TA scaffold was investigated via a full-thickness wound model. In addition, the histopathological and immunohistochemical (IHC) stainings of transforming growth factor-ß1(TGF-ß1) and tumor necrosis factor-α (TNF-α) were assessed. The results indicated an enhanced wound closure rate, effective collagen deposition, quick re-epithelialization, more skin appendages, and replacement of defect area with normal skin tissue by Bi-TA scaffold compared to other groups. Additionally, the regulation of TGF-ß1 and TNF-α was observed by Bi-TA dressing. Overall, the Bi-TA with appropriate structural and multifunctional properties can be an excellent candidate for developing effective dressings for wound healing applications.

Evaluation of a novel bioactive wound dressing: an in vitro and in vivo study.

OBJECTIVE: Hard-to-heal wounds, such as pressure ulcers and diabetic ulcers, are a major challenge for wound dressings. The aim of this study was to develop a bioactive dressing based on polymers and natural materials with unique biological and therapeutic properties. METHOD: The dressing was composed of an active layer containing polyvinyl alcohol (PVA), honey, curcumin and keratin, and an upper layer with lower hydrophilicity comprising PVA to induce flexibility. Physicochemical properties of the dressing were characterised by Fourier transform infrared spectroscopy, field emission scanning electron microscopy, swelling behaviour and antibacterial measurements. A wound healing study was performed using an experimental rat model and two different compositions of the bioactive dressing were compared with a commercial wound dressing (Comfeel, Coloplast, Denmark). Histopathological evaluation was conducted for this purpose. RESULTS: Characterisation results showed that a smooth bilayer film with two homogenous but distinct layers was produced. The dressing also provided adequate moisture to the wound environment without infection and adhesion due to dryness occurring. Our results exhibited significant bactericidal activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria and improved the wound healing process without any scarring. Histopathological findings demonstrated a significant higher healing rate in vivo together with well-formed epidermis, granulation tissue formation and tissue contraction, when compared with the commercial wound dressing. CONCLUSION: Our results demonstrated acceptable physical and healing effects for the novel bioactive wound dressing; however, more investigations are recommended.

The Beneficial Effects of Actinomycetales Immune Modulators in the Pancreas of Diabetic Rats.

Purpose: Type 1 diabetes mellitus (T1DM) has dramatically increased in recent years, especially in young people, and limits the life quality of the patients involved. Thus, many researchers are performing extensive studies to find alternative treatments for DM. Methods: Here, we evaluated the improvement effects of the heat-killed Actinomycetales species, including Gordonia bronchialis, and Tsukamurella inchonensis in streptozotocin (STZ)- diabetic rats by biochemical, immunological, and histopathological examinations. Results: The present findings exhibited a dramatic and progressive alteration in the serum levels of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) in the diabetic group, which were related to the blood glucose and insulin levels, oxidative stress defense (evaluated by TAC and MDA activities), and the pancreas biochemical indicators (such as amylase and lipase). More importantly, the present results were consistent with the histopathological findings, which included cellular degeneration, vascular congestion, hemorrhage, focal necrosis associated with mononuclear cell infiltration. Interestingly, all of the diabetic changes in the blood serum and tissues improved remarkably in the treated groups by Actinomycetales species. Conclusion: Surprisingly, most of the current diabetic complications effectively attenuated after oral administration of both Actinomycetales species, particularly with a high dose of T. inchonensis. Thus, it is concluded that the heat-killed Actinomycetales species can prevent and improve the progression of T1DM and its various complications profoundly.

Soluble P-selectin, procalcitonin, transforming growth factor (TGF)-ß and apo-proteins in association with the components of metabolic syndrome in obese individuals.

BACKGROUND & AIMS: Metabolic syndrome (MetS) is a clinical disorder with widespread prevalence. In the current study, we aimed to investigate the association between serum soluble P-selectin, procalcitonin, transforming growth factor (TGF)-ß and apo-proteins with the components of metabolic syndrome in obese individuals. MATERIAL AND METHODS: Sixty two obese patients with MetS and sixty five obese apparently healthy controls were participated in the current case-control study. The participants' anthropometric assessments and systolic and diastolic blood pressure (SBP and DBP) were measured. Serum lipids and the concentrations of ox-LDL, P-selectin, procalcitonin, TGF-ß and apo-proteins were measured with commercial ELIZA kits. RESULTS: Serum TG and TC were significantly higher in obese subjects with MetS; while TGF-ß, procalcitonin, apoprotein B and insulin concentrations were higher in obese non- MetS group. In obese subjects with MetS, procalcitonin was in positive association with ox-LDL and apoprotein-B was in positive association with HDL. In obese subjects without MetS, apoprotein -B was in positive association with WC and HDL and WC. CONCLUSION: The current study found several associations between serum lipids and PCT and serum apo-proteins in obese individuals either with or without MetS. Further studies with large sample size are warranted to better elucidate the observed relationships and underlying mechanism. TRIAL REGISTRATION: Not Applicable.

Nephrotoxic effects caused by co-exposure to noise and toluene in New Zealand white rabbits: A biochemical and histopathological study.

The biological and renal effects made by simultaneous and non-simultaneous exposure to toluene and noise were investigated. Twenty-four New Zealand white rabbits were exposed to 100 dB of white noise and 1000 ppm of toluene vapor for two weeks. The examined biochemical factors were urea, uric acid, creatinine, glucose, triglyceride, cholesterol, and albumin serum levels, measured on different days after the end of the exposure. Moreover, glutathione peroxidase activity (GPX), malondialdehyde dismutase activity (MDA), and superoxide dismutase (SOD) parameters were measured in the kidney tissue. The hematoxylin and eosin staining method was used for histopathological experiments. Overall, the noise increased albumin, uric acid, creatinine, and glucose levels, but it decreased urea, cholesterol, and triglyceride levels. Toluene decreased albumin, uric acid, and urea levels, while it increased creatinine, triglyceride, cholesterol, and glucose levels. Simultaneous exposure to noise and toluene decreased albumin, uric acid, cholesterol, and urea levels, whereas it increased creatinine, glucose, and triglyceride levels. GPX, MDA, and SOD levels increased by simultaneous and non-simultaneous exposure to noise and toluene. Furthermore, massive tubular degeneration, tubular cell vacuolization, glomerular disorganization, congestion, glomerular cell shrinkage, and unclear brush border were detected in the kidney tissue.

Effects of conjugated linoleic acid supplementation on serum levels of interleukin-6 and sirtuin 1 in COPD patients.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation and accelerated inflammaging of the lungs. Some studies showed that conjugated linoleic acid (CLA) has anti-inflammatory effects. The aim of the present study was to evaluate the effect of CLA supplementation on serum levels of interleukin (IL)-6 and sirtuin1 (SIRT1) in patients with COPD. MATERIALS AND METHODS: 82 patients with stable COPD were enrolled in a double blind clinical trial. Subjects were randomly assigned to two groups: placebo (n=42) and 3.2 g CLA daily supplementation (n=40). Forced expiratory volume in one second (FEV1%), BODE index, and serum levels of IL-6, and SIRT1 were measured at the baseline and six weeks after the intervention. In addition, the study parameters in the two groups were compared based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. RESULTS: After supplementation with CLA, serum levels of IL-6 and BODE index significantly decreased (p<0.05 and p<0.001, respectively). In addition, serum levels of SIRT1 (p<0.01) and FEV1 (p<0.001) significantly increased in the supplementation group. Based on GOLD criteria, the increase in SIRT1 and the decrease in IL-6 serum levels were found to be statistically significant in stages III and IV in the supplementation group (p<0.05 and p<0.01, respectively). CONCLUSION: Supplementation with CLA can modify the inflammatory markers and improve the health status of COPD patients. The results suggest that CLA supplementation in COPD patients can be useful in the management of the disease.