Improvement effects of transplanting pancreatic islet that previously incubated with biomaterials on the diabetic nephropathy in STZ- diabetic rats.

BACKGROUND: Islet transplantation is an effective treatment for diabetes or even its complications. Aim of this study is to investigate efficacy of biomaterial treated islet transplantation on treating diabetic nephropathy. METHODS: Male rats were randomly divided into 6 groups; Control, diabetic control, diabetic transplanted with untreated islets, with platelet rich plasma treated islets, with pancreatic islets homogenate treated islets, or with these biomaterials combination treated islets. Islets cultured with biomaterials and transplanted to diabetic rats. After 60 days, biochemical, oxidative stress, and stereological parameters were assessed. RESULTS: Serum albumin and BUN concentration, decreased and increased respectively, Oxidative stress of kidney impaired, kidney weight, volume of kidney, cortex, medulla, glomerulus, proximal and distal tubules, collecting ducts, vessels, inflammatory, necrotic and fibrotic tissue in diabetic group increased compared to control group (p < 0.001). In treated groups, especially pancreatic islets homogenate treated islets transplanting animals, there was significant changes in kidney weight, and volume of kidney, proximal and distal tubules, Henle's loop and collecting ducts compared with diabetic group (p = 0.013 to p < 0.001). Combination treated islets animals showed significant increase in vessel volume compared to diabetic group (p < 0.001). Necrotic and fibrotic tissue significantly decreased in islets treated than untreated islet animals, it was higher in pancreatic islets homogenate, and combination treated islets groups (p = 0.001). CONCLUSIONS: Biomaterials treated islets transplanting could improve diabetic nephropathy. Improvement of oxidative stress followed by controlling glucose level, and effects of growth factors presenting in biomaterials can be considered as capable underlying mechanism of ameliorating inflammatory, necrotic and fibrotic tissue volume.

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

BACKGROUND: The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. MATERIALS AND METHODS: This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. RESULTS: A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). CONCLUSION: This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Boosting wound healing in diabetic rats: The role of nicotinamide riboside and resveratrol in UPR modulation and pyroptosis inhibition.

BACKGROUND: Diabetes-related skin ulcers provide a substantial therapeutic issue, sometimes leading to amputation, needing immediate practical treatments for efficient wound care. While the exact mechanisms are unknown, pyroptosis and deregulation of the unfolded protein response (UPR) are known to exacerbate inflammation. Nicotinamide Riboside (NR) and Resveratrol (RV), which are known for their Nicotinamide adenine dinucleotide (NAD+) boosting and anti-inflammatory properties, are being studied as potential treatments. The purpose of this study was to shed light on the underlying molecular mechanisms and explore the medical application of NR and RV in diabetic wound healing. METHODS: 54 male Sprague-Dawley rats divided into control, diabetic (DM), Gel Base, DM-NR, DM-RV, and DM-NR + RV. Rats were orally administered 50 mg/kg/day of RV and 300 mg/kg/day of NR for 5 weeks. Following diabetes induction, their wounds were topically treated with 5 % NR and RV gel for 15 days. The wound closure rate, body weight, and serum lipid profiles were examined. Gene expression study evaluated UPR and pyroptosis-related genes (BIP, PERK, ATF6, IRE1α, sXBP1, CHOP, NLRP3, caspase-1, NFκB, and IL1-ß) in wound tissues, alongside histological assessment of cellular changes. RESULTS: NR and RV treatments greatly enhanced wound healing. Molecular investigation demonstrated UPR and pyroptosis marker modifications, suggesting UPR balance and anti-inflammatory effects. Histological investigation demonstrated decreased inflammation and increased re-epithelialization. The combination of NR and RV therapy had better results than either treatment alone. CONCLUSION: This study shows that NR and RV have therapeutic promise in treating diabetic wounds by addressing UPR dysregulation, and pyroptosis. The combination therapy is a viable strategy to improving the healing process, providing a multimodal intervention for diabetic skin ulcers. These findings pave the way for additional investigation and possible therapeutic applications, giving hope for better outcomes in diabetic wound care.

Proton-pump inhibitor-induced bone loss is preventable by concomitant use of a long-acting somatostatin analogue.

Objectives: Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model. Materials and Methods: Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis. Results: The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (P<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (P<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group. Conclusion: This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.

Comparison effect of collagen/P3HB composite scaffold and human amniotic membrane loaded with mesenchymal stem cells on colon anastomosis healing in male rats.

Covering surgical wounds with biomaterials, biologic scaffolds, and mesenchymal stem cells (MSCs) improves the healing process and reduces postoperative complications. This study was designed to evaluate and compare the effect of MSC-free/MSC-seeded new collagen/poly(3-hydroxybutyrate) (COL/P3HB) composite scaffold and human amniotic membrane (HAM) on the colon anastomosis healing process. COL/P3HB scaffold was prepared using freeze-drying method. MSCs were isolated and characterized from rat adipose tissue. After biocompatibility evaluation by MTT assay, MSCs were seeded on the scaffold and HAM by micro-mass seeding technique. In total, 35 male rats were randomly divided into five groups. After the surgical procedure, cecum incisions were covered by the MSC-free/MSC-seeded scaffold or HAM. Incisions in the control group were only sutured. One month later, the healing process was determined by stereological analysis. The Kruskal-Wallis followed by Dunn's tests were utilized for statistical outcome analysis (SPSS software version 21). COL/10% P3HB scaffold showed the best mechanical and structural properties (7.86 MPa strength, porosity more than 75%). MTT assay indicated that scaffold and especially HAM have suitable biocompatibility. Collagenization and neovascularization were significantly higher, and necrosis was considerably lower in all treated groups in comparison with the controls. MSC-seeded scaffold and HAM significantly decrease inflammation and increase gland volume compared with other groups. The MSC-seeded HAM was significantly successful in decreasing edema compared with other groups. Newly synthesized COL/P3HB scaffold improves the colon anastomosis healing; however, the major positive effect belonged to HAM. MSCs remarkably increase their healing process. Further investigations may contribute to confirming these results in other wound healing.

Pantoprazole-Induced Bone Loss through Gastrin Secretion: A Stereological Study.

Background: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. Methods: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation. Results: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. Conclusion: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.

Simple methods for cerebrospinal fluid collection in fetal, neonatal, and adult rat.

BACKGROUND: Cerebrospinal fluid (CSF) collection and its analysis are common medical practices useful in the diagnosis, therapy, and prevention of central nervous system (CNS) disorders. In recent years, several types of research have improved our insight into CSF and its role in health and disease. Yet, many characteristics of this fluid remain to be fully understood. NEW METHODS: Here, we describe how to collect CSF from embryonic, postnatal, and adult stages of the rat. In adults, CSF can be collected through simple stereotaxic surgery to expose the membrane overlying the cisterna magna (CM) of an anesthetized rat and collection of CSF through micropipette puncture through the membrane. In embryos and pups, CSF is aspirated, using a fire-polished micro-capillary pipette, from the CM of animals. RESULTS: Application of these methods provides the maximum volume of pure, uncontaminated CSF (embryonic day 19: 10-15 microliter, postnatal day 5: 20-30 microliter, adults: 100-200 microliter) with a success rate of approximately 95% in every age. COMPARISON WITH EXISTING METHODS: Compared to the existing protocols, these methods obtain considerable volumes of CSF, which may accelerate the measurement of biological markers in this fluid. Also, these techniques do not require surgical skills and according to the practical points mentioned during sampling, the procedures can be performed in rapid fashion. CONCLUSION: We describe simple methods for collecting CSF in live rats. These protocols provide clean, uncontaminated CSF for experiments to understand the exact role of this fluid in the development and maintenance of the CNS health.

Hydroalcoholic extract of Glycyrrhiza glabra root combined with Linum usitatissimum oil as an alternative for hormone replacement therapy in ovariectomized rats.

Objective: Plant-derived estrogens (phytoestrogens) with structural similarity to primary female sex hormones could be suitable replacements for sex hormones. Therefore, the effects of the licorice root extract and Linum usitatissimum oil on biochemical and hormonal indices in the serum and uterine stereological changes in ovariectomized rats were evaluated. Design: In this study, 70 adult female rats were randomly divided into seven groups including 1) control group, 2) sham-operated group, 3) ovariectomized (OVX) group, 4) OVX rats that received 1 mg/kg estradiol for 8 weeks at the day of post-operation, 5) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil for 8 weeks at the day of post-operation, 6) OVX rats which received 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation, and 7) OVX rats which received 2.0 mg/kg body wt Linum usitatissimum oil + 2.0 mg/kg body wt licorice extract for 8 weeks at the day of post-operation. After eight weeks, alkaline phosphatase activity, as well as calcium, estradiol, and progesterone concentrations were assessed and tissue samples of the uterus were serologically examined. Results: The results indicated that after 8 weeks of OVX the alkaline phosphatase activity (Mean = 637.7 IU/L) increased and the calcium (Mean = 7.09 mg/dl), estradiol (5.30 pmol/L), and progesterone (Mean = 3.53 nmol/L) reduced compared to other groups. Moreover, stereological changes in the uterus in ovariectomy groups were seen compared to the other groups. The treatment with Linum usitatissimum oil and licorice extract had a significant therapeutic effect on biochemical factors and stereological changes compared to the ovariectomized group. Conclusion: The results of this study showed that the combination of Linum usitatissimum oil with licorice extract showed the high potential of hormone replacement therapy in the reduction of OVX complications.

Potential Anti-Inflammatory and Growth Inhibitory Effect of Cyrtopodion scabrum Extract on Colon Cancer; An in vivo Study.

BACKGROUND: The use of complementary and/or alternative medicine to increase the efficacy and decrease the side effects of current cancer treatment is highly required. In this in-vivo study, we aimed to investigate the anti-tumor activity and probable side effects of a natural treatment, Cyrtopodion scabrum extract (CsE), in a model of tumor bearing mice. METHODS: We established 28 female CT26-tumor bearing balb/c-mice model. We divided them randomly into four groups (n=7): Negative control received distilled water (DW) and the three treatment groups were administered with 5-FU and two different doses (300 and 600 mg/kg) of the gecko aqueous extract, respectively. The changes in the tumor volumes and weights during and after treatment, along with the blood cell counts; spleen and thymus indices were assessed in the treatment groups. We have also measured the serum TNF-α, VEGF, AST, ALT and GSH, as well as the physical activities of the experimental mice. RESULTS: We found that the means of tumor weights and volumes in both CsE and 5-FU treated groups were significantly lower than the untreated group (p<0.05). Serum TNF-α and VEGF levels in both CsE treated groups were remarkably lower than 5-FU and untreated groups (p<0.05). The 5-FU treatment caused a remarkably decrease in serum GSH, RBC count, WBC count, thymus index, and spleen index , while CsE treatment maintained these quantities, with no significant changes, compared to the control group. AST and ALT were not significantly changed in none of the treated groups compared to control. CONCLUSION: Altogether, data suggest C. scabrum, as an effective and safe anti-cancer natural source, which could be used as an alternative/complementary medicine for the treatment of patients who suffer from colon cancer.

Recombinant GPEHT Fusion Protein Derived from HTLV-1 Proteins with Alum Adjuvant Induces a High Immune Response in Mice.

The human T-cell leukemia virus type 1 (HTLV-1) is a positive single-stranded RNA virus that belongs to the delta retrovirus family. As a result, a vaccine candidate that can be recognized by B cells and T cells is a good candidate for generating a durable immune response. Further, the GPEHT protein is a multi-epitope protein designed based on the Gag, Pol, Env, Hbz, and Tax proteins of HTLV-1. In developing a suitable and effective vaccine against HTLV-1, the selection of a designed protein (GPEHT) with the formulation of an alum adjuvant was conducted. In this study, we assessed the potential of a multi-epitope vaccine candidate for stimulating the immune response against HTLV-1. In assessing the type of stimulated immune reaction, total IgG, IgG1, and IgG2a isotypes, as well as the cytokines associated with Th1 (IFN-γ), Th2 (IL-4), and Th17 (IL-17), were analyzed. The outcomes showed that the particular antisera (total IgG) were more elevated in mice that received the GPEHT protein with the alum adjuvant than those in the PBS+Alum control. A subcutaneous vaccination with our chimera protein promoted high levels of IgG1 and IgG2a isotypes. Additionally, IFN-γ, IL-4, and IL-17 levels were significantly increased after spleen cell stimulation in mice that received the GPEHT protein. The immunogenic analyses revealed that the GPEHT vaccine candidate could generate humoral and cell-mediated immune reactions. Ultimately, this study suggests that GPEHT proteins developed with an alum adjuvant can soon be considered as a prospective vaccine to more accurately evaluate their protective efficacy against HTLV-1.

Primary hepatocyte urea assessment in the sodium-alginate patterned hydrogel by electrochemical procedure containing umbilical cord conditioned media.

Limitations in liver transplantation and advances in cell therapy methods motivated us to study primary hepatocytes. The main challenge in using primary hepatocytes for liver regeneration is that they lose their functionalities. We aimed to develop a controlled-shape hydrogel and apply the conditioned-media of mesenchymal stromal cells (CM-MSCs) to improve in vitro hepatocyte functions. In this experimental study, following rat hepatocyte isolation by collagenase perfusion and collection of human umbilical cord CM-MSCs, a simple and precise system called electrodeposition was used to produce the patterned alginate hydrogel. To reduce the cytopathic effects, we used an indirect electrodeposition method. For characterizing this structure, mechanical properties, Fourier-transform infrared spectroscopy (FTIR), water uptake, in-vitro degradation, and hydrogel stability were studied. Urea synthesis as a basic function of hepatocytes was assessed in five different groups. Scanning electron microscope (SEM) was utilized to evaluate the primary hepatocyte morphology and their dispersion in the fabricated structure. We observed a significant increase in urea synthesis in the presence of CM-MSCs in patterned hydrogel alginate compared to 2D culture on day 3 (p<0.05). However, there was no significant difference in simple and patterned hydrogel on day 2. We found that the electrodeposition method is appropriate for the rapid fabricating of hydrogel structures with arbitrary patterns for 3D cell culture.

New concepts in regulation and function of the FGF23.

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.

Thymoquinone improves folliculogenesis, sexual hormones, gene expression of apoptotic markers and antioxidant enzymes in polycystic ovary syndrome rat model.

BACKGROUND: Nowadays, polycystic ovary syndrome (PCOS) is a prevalent cause of infertility affecting women of reproductive age around the world. Thymoquinone is a natural antioxidant, derived from Nigella sativa. OBJECTIVES: The current study aimed to evaluate the protective effects of thymoquinone on the detrimental effects of PCOS rats induced with letrozole. METHODS: Thirty-two female rats were randomly divided into four groups: (1) Control, (2) PCOS, (3) PCOS+5 mg/kg thymoquinone and (4) PCOS+10 mg/kg thymoquinone. Thymoquinone was administered every 3 days for 30 days. Ovaries were histopathologically and stereologically examined, and antioxidant and apoptotic enzymes gene expression in ovaries and sex hormones in serum were measured. RESULTS: The number of unilaminar, multilaminar, antral, and graffian follicles, volume density of corpus luteum (p < 0.01), and GPx1 gene expression in ovaries and level of FSH in the blood increased in both thymoquinone groups when compared to untreated PCOS (p < 0.05). Ovaries in thymoquinone groups showed a significant reduction in the number of atretic follicles, ovary weight and volume, volume density of cortex and ovarian cysts, Bax gene expression (p < 0.01) and Bax/Bcl2 ratio as well as levels of luteinizing hormone (LH), LH/FSH ratio and testosterone (p < 0.05) in the blood of female rats when compared to PCOS group. Administration of thymoquinone restored the most detrimental effects of PCOS on ovaries (p < 0.01) and sexual hormones (p < 0.05) in rats. CONCLUSIONS: These data suggest that thymoquinone has improved effects on ovarian function in the PCOS rat model. Therefore, thymoquinone might be useful as a protective agent and adjunct treatment in PCOS patients.

Evaluation of morphology and angiogenesis of breast cancer in BALB/c mice using trypsin inhibitor from Cucumis melo seeds. In vitro and in vivo study.

Introduction: Melon seeds, as an excellent source of protease inhibitors, may have a protective role against tumor progression and angiogenesis. However, their effects on angiogenesis and the mechanism of their action against cancer progression remain elusive. This study aimed to investigate the effect of bioactive compounds of melon seed on the expression of angiogenesis genes in BALB/c mice with breast cancer. Material and methods: Trypsin inhibitor (TI) was purified from the seed powder of Cucumis melo. Half- maximal inhibitory concentration was determined for TI, extract of melon seed powder (EXT), and tamoxifen (TAM) by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Also, breast tumor was induced by subcutaneous injection of MC4-L2 cells in BALB/c inbred mice breast tissue. After tumor growth, mice were treated with TI, EXT, and TAM to examine their effects on the tumor characteristics and expression of angiogenesis-related genes including MMP-2, MMP-9, and vascular endothelial growth factor (VEGF) using the reverse transcription polymerase chain reaction method. Results: Trypsin inhibitor, EXT, TAM, and adjuvant treatment of TI + TAM resulted a reduction in expression of MMP-2, MMP-9, and VEGF. All treatments improved the breast tumor characteristics and the necrosis. The real-time polymerase chain reaction method verified the positive effects of the treatments on the breast cancer cell line and tumors. Conclusions: The results indicated that treatments with TI purified from Cucumis melo seeds and also combination therapy of TI and TAM can be considered as an alternative therapy in breast cancer patients. Further studies are warranted.

The protective effect of L-carnitine on testosterone synthesis pathway, and spermatogenesis in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats. METHODS: Sixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed. RESULTS: L-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p < 0.05). Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group. CONCLUSION: The study's findings demonstrated that L-carnitine due to its anti-oxidant properties, ameliorated the reproductive abnormalities in the male rats exposed to MSG.

The ameliorative role of specific probiotic combinations on bone loss in the ovariectomized rat model.

BACKGROUND: Osteoporosis, a skeletal disease described by impaired bone strength, cause an increased risk of fractures. We aimed in this study to clarify which particular wise combination of probiotics has the most beneficial effect in the rat model of osteoporosis. METHODS: Sixty-three mature female Sprague Dawley rats (12-14 weeks old, weight 200 ± 20 g) were ovariectomized and then divided into nine random groups, each group consisting of 7 rats. Lactic acid bacteria were isolated from traditional fermented yogurt on the northern coast of the Persian Gulf. Seven combinations of probiotics, each containing three probiotic strains, were designed and administered (1 × 10 9 CFU / ml/strain daily along with their water) to treat ovariectomized rats. The period from ovariectomy to eutanásia was 3 months. For evaluating femur, spine, and tibia, bone mineral density (BMD), and bone mineral content (BMC), Dual-energy X-ray absorptiometry (DEXA) scans were performed. Also, effect of probiotic combinations was assessed on biochemical markers including vitamin D, calcium, phosphorus, and alkaline phosphatase in serum. RESULTS: Combination NO 4, containing L. acidophilus, B. longum, and L. reuteri, is the most influential group on global, spine, and femur BMD. Combination NO 3, containing L. acidophilus, L. casei, and L. reuteri, also significantly affects the BMD of the tibia among the treatment group. We found that the combination NO 4 had the most significant ameliorative effect on global BMC. Also, combination NO 1 (comprising L. acidophilus, L. casei, and B. longum), NO 6 (containing L. casei, B. longum, and Bacillus coagulans), NO 7 (containing L. casei, L. reuteri, and B. longum), and NO 4 had the most considerable raising effect on spine BMC. In addition, the serum calcium and Vitamin D concentration in the groups NO 4, 6, and 7 were significantly higher than in OVX groups, whereas the alkaline phosphatase concentration was considerably reduced in these groups. CONCLUSION: Among nine effective probiotics, a combination containing L. acidophilus, B. longum, and L. reuteri is the most influential group in ovariectomized osteoporotic rat.

Resveratrol promotes liver cell survival in mice liver-induced ischemia-reperfusion through unfolded protein response: a possible approach in liver transplantation.

BACKGROUND: Ischemia-reperfusion (I/R) of the liver is a multifactorial condition that happens during transplantation and surgery. The deleterious effects of I/R result from the acute production of reactive oxygen species (ROS), which can trigger immediate tissue damage and induce a series of destructive cellular responses, including apoptosis organ failure and inflammation. The production of ROS in the I/R process can damage the antioxidant system and cause liver damage. Resveratrol has been shown to have antioxidant properties in several investigations. Here, we address the therapeutic effect of resveratrol on I/R-induced liver injury by focusing on unfolded protein response (UPR) signaling pathway. METHODS: Five minutes before reperfusion, resveratrol was injected into the tail vein of mice. They were ischemic for 1 h and then re-perfused for 3 h before being slaughtered (I/R). The activity of liver enzymes and the expression levels of genes involved in the unfolded protein response pathway were used to measure the hepatic damage. RESULTS: Our results revealed that the low dose of resveratrol (0.02 and 0.2 mg/kg) post-ischemic treatment significantly reduced the ALT and AST levels. In addition, compared with the control group, the expression of UPR pathway genes GRP78, PERK, IRE1α, CHOP, and XBP1 was significantly reduced in the resveratrol group. In the mice that received lower doses of resveratrol (0.02 and 0.2 mg/kg), the histopathological changes induced by I/R were significantly improved; however, the highest dose (2 mg/kg) of resveratrol could not significantly protect and solve the I/R damage. CONCLUSION: The findings of this study suggest that hepatic ischemia occurs after liver transplantation and that receiving low-dose resveratrol treatment before reperfusion may promote graft survival through inhibition of UPR arms, especially PERK and IRE1α.

Investigating the Effect of Hydroalcoholic Extract of Licorice Root to Prevent Ovariectomy-Mediated Complications.

Introduction: The importance of women's health and the quality of life after menopause is a critical issue. To prevent disability and menopause complications as well as avoid the side effects of hormone replacement therapy (HRT), in this study, licorice hydroalcoholic extract (Glycyrrhiza uralensis roots) was evaluated as a natural remedy. Methods: Seventy-two female Sprague-Dawley rats were divided into six groups: control group, Sham-operated group, Glycyrrhiza (Gly) 30% group, and ovariectomized group as well as two ovariectomized groups treated with Gly 10% and Gly 30%. Normal saline and different treatments were administered orally for 8 weeks. At the end of the study, calcium, alkaline phosphatase, estrogen, and progesterone levels in the ovariectomized rats were determined. Moreover, the stereological and histopathological changes in uterine tissue in all groups were determined. Phytochemical analyses were also performed to determine the total phenolic content and antioxidant potential of the extract. Result: The hydroalcoholic extract of licorice root exhibited considerable effect to improve calcium, estrogen, and progesterone levels in the ovariectomized rats. Also, hydroalcoholic extract of licorice root successfully decreases the amount of alkaline phosphatase (ALP) level. The stereological and histopathological findings confirmed the therapeutic potential of this extract. The considerable effects of hydroalcoholic extract of licorice root could be due to high amounts of phytoestrogens with similar estrogen-like structures. Considerable total phenolic content and antioxidant activity were also seen in licorice root extract. Conclusion: Hydroalcoholic extract of licorice root due to containing high amounts of phytoestrogens with similar chemical structures to estradiol notably improves biochemical parameters as well as stereological and histopathological markers of uterine tissues in ovariectomy rats, so it could be a potential agent for prevention and/or treatment as hormone replacement therapy in healthy middle-aged and/or older women.

The effect of hydroalcoholic extract of Psidium guajava L. on experimentally induced oral mucosal wound in rat.

BACKGROUND: The aim of this study was to evaluate the biological effects of hydroalcoholic extract of Psidium guajava L leaves and phenytoin as a standard agent on the induced oral mucosal wound. METHODS: Hundred seventy Sprague Dawley rats were grouped in 5 clusters randomly. Oral mucosal wounds were induced in all rats except for the control group. Phenytoin and guajava leaf extract were used as a mouthwash. Twelve rats from the 5 groups were euthanized on day 7th and 10th, and 10 rats from each group were sacrificed on the 14th day. Interleukin-6 and total antioxidant capacity were determined in the serum. The tissues were evaluated for pathological and stereological assessments. Phytochemical analyses were performed on the hydroalcoholic extract of Psidium guajava L to determine the antioxidant potency. RESULTS: Total phenolic content test and DPPH analysis demonstrated the high potential of antioxidant capacity of Psidium guajava L. Decreasing IL-6 and increasing TAC were seen in the guajava hydroalcoholic extract and phenytoin groups. The difference of IL-6 between the wound treated guajava group and the wounded group was significant. The wound treated guajava group and wound treated phenytoin group on the 14th day increased the number of fibroblast cells and volume density of sub-mucosae effectively to the same thickness to be considered as a healed sub-mucosae layer. The volume density of the epithelium changes showed statistically significant different responses based on gender. CONCLUSION: In conclusion, hydroalcoholic extract of Psidium guajava L leaves might exert theraputic effects on oral mucositis.

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration.

BACKGROUND: Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model. METHODS: This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed. RESULTS: Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05). CONCLUSION: In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.