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Abstract Background The probiotic potential of Lacticacid bacteria has been studied in various medical complications, from gastrointestinal diseases to antibiotic resistance infections recently. Moreover, diabetic ulcer (DU) is known as one of the most significant global healthcare concerns, which comprehensively impacts the quality of life for these patients. Given that the conventional treatments of DUs have failed to prevent later complications completely, developing alternative therapies seems to be crucial. Methods We designed the stable oleogel-based formulation of viable probiotic cells, including Lactobacillus rhamnosus (L. rhamnosus), Lactobacillus casei (L. casei), Lactobacillus fermentum (L. fermentum), and Lactobacillus acidophilus (L. acidophilus) individually to investigate their effect on wound healing process as an in vivo study. The wound repair process was closely monitored regarding morphology, biochemical, and histopathological changes over two weeks and compared it with the effects of topical tetracycline as an antibiotic approach. Furthermore, the antibiofilm activity of probiotic bacteria was assessed against some common pathogens. Results The findings indicated that all tested lactobacillus groups (excluded L. casei) included in the oleogel-based formulation revealed a high potential for repairing damaged skin due to the considerably more levels of hydroxyproline content of tissue samples along with the higher numerical density of mature fibroblasts cell and volume density of hair follicles, collagen fibrils, and neovascularization in comparison with antibiotic and control groups. L. acidophilus and L. rhamnosus showed the best potential of wound healing among all lactobacillus species, groups treated by tetracycline and control groups. Besides, L. rhamnosus showed a significant biofilm inhibition activity against tested pathogens. Conclusions This experiment demonstrated that the designed formulations containing probiotics, particularly L. acidophilus and L. rhamnosus, play a central role in manipulating diabetic wound healing. It could be suggested as an encouraging nominee for diabetic wound-healing alternative approaches, though further studies in detailed clinical trials are needed.

Abstract Background This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis. Methods Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties. Results The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected. Conclusion This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis.

Abstract 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

Objective(s): 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

Objective: To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome (PCOS) rats. Methods: Fifty female Sprague-Dawley rats were randomly divided into five groups: the control group, the ethanol group, the quercetin group (15 mg/kg/day), the PCOS group, as well as the PCOS + quercetin group. After the induction of PCOS, quercetin was administered orally for 30 days. Histological, stereological and real-time PCR analyses were carried out to evaluate the effect of quercetin on PCOS rats. Results: Stereological analysis revealed that quercetin significantly increased the number of ovarian follicles and the volume of corpus luteum and induced a significant decrease in atretic follicles in comparison to the PCOS group. In addition, quercetin markedly increased mTOR gene expression while decreasing Beclin-1 and LC3 gene expression. Conclusions: Quercetin strongly modulates the expression of ovarian autophagy-related genes and stereological parameters in PCOS rats. Therefore, it can be considered as an ameliorative component for ovarian follicular impairments.

Abstract 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

Abstract 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

Abstract 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.

Abstract 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.

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.

Abstract 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.

Abstract 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

Background: Paricalcitol has been proposed for the treatment of secondary hyperparathyroidism in patients with renal failure and vitamin D deficiency (VDD); however, VDD is related to a range of clinical complaints. We aimed to investigate the effects of paricalcitol on body composition in VDD rats.Methods: Thirty adult male rats aged 10 weeks were randomly divided into three groups of 10, comprising control, VDD, and VDD plus paricalcitol (32 ng/rat intraperitoneal injection) (VDD+P), at the Animal Lab of the Endocrinology and Metabolism Research Center, Shiraz, Iran, in 2020. Body composition was assessed after three weeks via serum biochemical tests and dual-energy X-ray absorptiometry. Finally, the data were analyzed by using the paired-sample t test, the one-way ANOVA, and the Tukey post hoc test.Results: Global lean mass and fat mass were lower in the VDD and VDD+P groups than in the controls (P

Abstract Background Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible damages induced by MSG effects on some organs have been stated in experimental animal models. The aim of the present study was to evaluate the protective effects of L-carnitine (L-ca) on the renal tissue in MSG-Induced Rats. Methods In this regard, 60 male rats were randomly divided into six groups (n = 10/each): 1 (Control); 2 (sham); 3 (L-carnitine 200 mg/kg b.w); 4 (MSG 3 g/kg b.w); 5 (MSG + L-carnitine 100 mg/kg); and 6 (MSG + L-carnitine 200 mg/kg). After 6 months, the rats were sacrificed, the blood sample collected and the kidneys harvested for evaluation of biochemical analytes, genes expression, and histopathological changes. Results MSG significantly increased the serum level of MDA, BUN, creatinine, uric acid and renal Caspase-9, NGAL and KIM-1 expression, but it decreased the serum activity also renal expression of SOD, catalase, GPX, and Bcl-2 expression compared to the control group. Treatment with L-ca significantly reduced the serum BUN, creatinine, uric acid and MDA level and increased catalase, GPX and SOD compared to the MSG group. However, only administration of L-ca 200 significantly decreased the caspase-9, NGAL and KIM-1; also, it increased the Bcl-2 expression in the kidney compared to the MSG group. Conclusions Our findings indicated that L-carnitine had a major impact on the cell protection and might be an effective therapy in ameliorating the complications of the kidney induced by MSG via its antioxidant and anti-apoptotic properties.

Abstract Background Post-menopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. Methods The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations for 4 weeks immediately after ovariectomy. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. Results Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global bone mineral density (BMD), Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMD. We found Bacillus coagulans supernatant meaningfully enriched tibia BMD. Conclusion Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.

Abstract The ovariectomized rat is a widely used preclinical model for studying postmenopausal and its complications. In this study, the therapeutic effect of flaxseed oil on the ovariectomized adult rats was investigated. Our results showed that biochemical parameters including calcium, oestrogen and progesterone levels increase 8 weeks after ovariectomy in rats. Also, the amount of alkaline phosphatase decreased significantly after 8 weeks compared with the OVX rat. The healing potential of flaxseed oil was proven by successfully recovering the affected tissue and preventing the unpleasant symptoms of ovariectomized rats. The biological effects of flaxseed oil may be due to high amounts of fatty acids, phytoestrogens and an array of antioxidants. The results suggest that flaxseed oil can mimic the action of oestrogen and can be a potential treatment for hormone replacement therapy (HRT).

Abstract Background Accumulating evidence suggests that low vitamin D status may affect male gonadal structure. This study was undertaken to reveal whether vitamin D-deficient rats have demonstrable changes in the quantitative histomorphometric properties of the testis. Methods In the present investigation, adult male Sprague-Dawley rats were divided into four groups and received: group 1) conventional diet; group 2) vitamin D-deficient diet; group 3) vitamin D-deficient diet and paricalcitol and group 4) conventional diet plus paricalcitol. After 3 months, serum levels of vitamin D metabolites, Ca, P, LH, FSH, testosterone, and epididymal sperm quality were evaluated. Moreover, the morphometric characteristics of testis were assessed via stereological methods. Results Rats fed a vitamin D-deficient diet (groups 2 and 3) were normocalcemic and had 25-hydroxyvitamin D3 level below 10 ng/mL. A significant reduction in serum testosterone and comparable gonadotropin levels were seen in vitamin D-deficient groups compared to controls. The concentration, morphology, and motility of sperm cells were profoundly disturbed in animals raised on the vitamin D-deficient diet. There was a significant decline in the population of different germ cells, the volume of interstitial tissue and germinal epithelium in group 2 and 3 rats, which were placed on the vitamin D-deficient diet. No appreciable difference in the estimates of the Leydig or Sertoli cell numbers were observed between groups. Conclusions The depletion of vitamin D stores and induction of moderate grades of vitamin D deficiency by dietary measures led to remarkable impairment of spermatogenesis and microscopic architecture of rat testis. These findings can be attributed, at least in part, to decreased androgen production.

Objective: Osteoporosis, as a skeletal disorder caused by aging, is considered a major health problem. This work was planned to assess the effect of the black olive hydroalcoholic extract on bone mineral density and biochemical parameters in ovariectomized rats. Materials and Methods: Ninety 6-month-old female Sprague Dawley rats were randomly assigned into 7 sets: control (received saline); sham-operated control, Ovariectomized (OVX) rats (received saline); 3 groups of black olive-supplemented OVX rats (respectively, receiving 250, 500, and 750 mg/kg body wt black olive extract orally); and estrogen group (receiving 3 mg/kg/day estradiol valerate). Blood samples were collected 2, 4 and 6 months after treatment to measure calcium (Ca), alkaline phosphatase (ALP), and phosphorus (P). Dual-energy X-ray absorptiometry (DEXA) was applied to measure the bone mineral density (BMD). Global, lumbar spine and lower limb BMD was measured. Results: Ca concentration was significantly increased in the group treated with the highest dose of black olive hydroalcoholic compared to the OVX group (p

Abstract Background Pioglitazone, as a PPAR gamma agonist, is used for the management of type 2 diabetes mellitus. Nevertheless, evidence showed that the therapeutic modulation of PPAR gamma activity using pioglitazone might be linked with bone mass reduction and fracture risk in type 2 diabetes mellitus patients. The objective of the current research was to inspect the preventive role of some types of probiotic strains, including (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) against pioglitazone-induced bone loss. Methods Streptozotocin (60 mg/kg) was administered for diabetes induction. Diabetic rats were fed orally with pioglitazone (300 mg/kg) and probiotics (1 × 109 CFU/ml/day) alone and in combination for four weeks. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD, BMC, and area of the femur, spine, and tibia at the end of the experiment. Serum glucose, serum calcium (Ca), alkaline phosphatase (ALP), phosphorus (P), Blood urea nitrogen (BUN), creatinine, and urine calcium were also analyzed. Results Administration of pioglitazone and probiotics alone and, in combination, significantly reduced elevated blood glucose. Pioglitazone treatment significantly increased urinary calcium and BUN and decreased ALP and creatinine. Co-treatment of probiotics with pioglitazone significantly decreased urinary calcium, creatinine, and ALP. Pioglitazone showed detrimental effects on femur-BMD, whereas treatment with probiotics remarkably ameliorated these effects. Among the tested probiotics, Bifidobacterium longum displayed the best protective effects on pioglitazone-induced bone loss in diabetic rats. Conclusion This study suggests probiotic supplementation in diabetic patients on pioglitazone regime could be considering as an excellent strategy to ameliorate bone loss induced by pioglitazone.

Abstract Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder. The aim of the present study was to evaluate the effects of the oral administration of thylakoid-rich spinach extract and the caraway aqueous extract in letrozole-induced polycystic ovary syndrome rats. Methods Sixty female Sprague-Dawley rats were randomly divided into five groups of 12 animals each. Letrozole (1 mg/kg) was administered orally for a period of 28 days to induce PCOS. Sham and PCOS control rats received 1 mL/day of distilled water, and the three groups of PCOS rats were given 150 mg/kg of metformin, 3 g/kg of caraway, and thylakoid at a dose of 6 mg chlorophyll/gr food intake/day by oral gavage for 8 weeks. Finally, blood samples were collected and the right ovary of rats was removed, weighed, and fixed in 4% buffered formalin to determine the biochemical and stereological parameters. Results Compared to the PCOS control group, consuming metformin, thylakoid, and caraway extracts significantly improved the fasting blood sugar (FBS), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), luteinizing hormone (LH), insulin resistance, and body weight, increased the volume of the corpus luteum, and reduced the number of atretic follicles after 8 weeks (푃

Background: Resveratrol and Berberis integerrima (B. integerrima) are known to be natural antioxidants and regulators of human metabolism. However, the effects of resveratrol and B. integerrima on the ovarian morphology in polycystic ovary syndrome (PCOS) are not obvious. Objective: This study aimed to determine the effect of the hydroalcoholic extract of B. integerrima in combination with resveratrol on some biochemical parameters and ovarian morphology in the letrozole-induced PCOS rat. Materials and Methods: Seventy adult female Sprague-Dawley rats aged 10-12 weeks weighing 200 ± 20 gr were randomly divided into seven groups (n = 10/each). Group I): normal; Group II): vehicle; Group III): letrozole-induced PCOS 1 mg/kg letrozole orally, rats receiving 1 cc normal saline orally; Group IV): PCOS + receiving 150 mg/kg metformin orally; Group V): PCOS + receiving 20 mg/kg resveratrol orally; Group VI): PCOS + 3 gr/kg barberry orally; and Group VII): PCOS + receiving 3 gr/kg barberry and 20 mg/kg resveratrol orally. All animals were followed-up for 63 days. The biochemical parameters and histological assessments of ovaries were performed. Results: Resveratrol alone and/or in combination with B. integerrima treatment in rats led to a significant decrease in low-density lipoprotein, triglyceride, malondialdehyde, and tumor necrosis factor-alpha concentrations (p = 0.02). The groups IV, V, VI, and VII showed a decrease in insulin resistance and an increase in the superoxide dismutase, total antioxidant capacity, and high-density lipoprotein (p = 0.01). No significant difference was observed between the level of serum glucose in the treatment groups. Number of cystic follicles had a significant decrease in barberry, resveratrol, and their combination groups (p < 0.001). Conclusion: Resveratrol, B. integerrima, and their combination as natural products with fewer side effects might be effective as an alternative medicine in treatment of PCOS.

Abstract Background Recent studies have reported that herbal extracts may have some protective effect against the complications of diabetes mellitus. This study aimed to investigate the effects of Achillea millefolium hydroalcoholic extract in comparison to metformin on liver damage, lipid abnormality, and glycemic control in diabetic rats. Methods Rats were randomly assigned to 7 groups of 10 animals. Diabetes was induced by injection of streptozotocin (STZ) to 4 groups of rats. Three groups of diabetic rats were given 250 mg/kg/day metformin, 25 mg/kg/day Achillea millefolium hydroalcoholic extract, or 100 mg/kg/day of this extract. Two non-diabetic groups were also given either 25 mg/kg/day or 100 mg/kg/day Achillea millefolium extract. Normal control and diabetic control rats received 1 mL/day of normal saline. Treatments were administered through oral gavage for 28 days. At the end, rats were anesthetized with ether and their serum samples were separated in order to measure blood glucose, serum total protein, lipids, and liver enzymes. Results There was a significant reduction in blood glucose, serum liver enzymes, triglycerides, and total- and LDL-cholesterol levels of the Achillea millefolium extract-treated groups compared to the other groups. In addition, there was a significant increment in body weight and HDL-cholesterol serum level in the Achillea millefolium-treated groups. Conclusion Achillea millefolium extract compared to metformin reduces lipid abnormality, blood glucose and liver enzymes in STZ-induced diabetic rats. Future clinical studies are warranted to confirm our experimental findings in humans.

Objective(s): Type 1 diabetes (T1D) is an autoimmune disease resulting from inflammatory destruction of islets β-cells. Nowadays, progress in cell therapy, especially mesenchymal stem cells (MSCs) proposes numerous potential remedies for T1D. We aimed to investigate the combination therapeutic effect of these cells with insulin and metformin on neuropeptide Y, melanocortin-4 receptor, and leptin receptor genes expression in TID. Materials and Methods: One hundreds male rats were randomly divided into seven groups: the control, diabetes, insulin (Ins.), insulin+metformin (Ins.Met.), Wharton’s Jelly-derived MSCs (WJ-MSCs), insulin+metformin+WJ-MSCs (Ins.Met.MSCs), and insulin+WJ-MSCs (Ins.MSCs). Treatment was performed from the first day after diagnosis as diabetes. Groups of the recipient WJ-MSCs were intraportally injected with 2× 10⁶ MSCs/kg at the 7th and 28th days of study. Fasting blood sugar was monitored and tissues and genes analysis were performed.Results: The blood glucose levels were slightly decreased in all treatment groups within 20th and 45th days compared to the diabetic group. The C-peptide level enhanced in these groups compared to the diabetic group, but this increment in Ins.MSCs group on the 45th days was higher than other groups. The expression level of melanocortin-4 receptor and leptin receptor genes meaningfully up-regulated in the treatment groups, while the expression of neuropeptide Y significantly down-regulated in the treatment group on both times of study. Conclusion: Our data exhibit that infusion of MSCs and its combination therapy with insulin might ameliorate diabetes signs by changing the amount of leptin and subsequent changes in the expression of neuropeptide Y and melanocortin-4 receptor.

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.

Objective: Oxidative stress leads to reactive oxygen species (ROS) overproduction, which causes tissue injury in diabetic patients. The aim of this study was to evaluate the effects of Zataria multiflora extract on TNF-α, oxidative stress products, and insulin levels as well as lipid profile in diabetic rats. Materials and Methods: Rats were randomly divided into 6 groups of 10 animals. Diabetes was induced by a single injection of streptozotocin (STZ). Control and diabetic control rats orally received 1 mL/day of normal saline, whereas the other three groups received 250, 500 and 1000 mg/kg/day of Z. multiflora extract, and one non-diabetic group orally received 1000 mg/kg/day Z. multiflora extract, for 28 days. At the end of the treatment course, rats were anesthetized and their serum samples were analyzed for TNF-α, malondialdehyde (MDA), super oxide dismutase (SOD), total antioxidant capacity (TAC), lipid profile, total plasma protein, blood glucose, insulin, and liver enzymes levels. Results: Our results showed that cholesterol, LDL, TG, MDA and TNF-α levels decreased, but HDL, SOD, TAC, and total protein increased significantly in the diabetic group receiving 1000 mg/kg Z. multiflora compared to the diabetic control group (P

Background: Several plants have been shown to possess antioxidant and estrogenic properties that can be useful in postmenopausal bone-loss prevention. The present study aimed to investigate the anti-osteoporotic effects of the hydroalcoholic extract of the Psidium guajava (PG) fruit in ovariectomized (OVX) rats. Methods: Sixty female Sprague–Dawley rats were randomly divided into 6 groups: a control positive group, a sham-operated group, an OVX group given normal saline (OVX-only group), and 3 treatment groups comprising 2 OVX groups treated orally with 500 and 1000 mg/kg/d of the hydroalcoholic extract of the PG fruit respectively and an OVX group treated with an injection of 0.15 mg/kg of estradiol. The study was conducted over a 12-week period. Samples from the animals’ blood, femoral bones, and uteri were collected for stereological and biochemical analyses. The data were analyzed using SPSS, version 19. A P value equal to or less than 0.05 was considered statistically significant. Results: The results revealed a significant decrease in the levels of calcium, total antioxidant capacity, and phosphorus as well as uterus weight, femoral ash density, femoral volume and weight, and numbers of osteocytes and osteoblasts. Moreover, there was an increase in the levels of alkaline phosphatase and urine deoxypyridinoline together with a rise in the number of osteoclasts in the OVX-only group compared to the control and treatment groups (P≤0.05). The hydroalcoholic extract of the PG fruit increased femoral weight and volume, femoral ash density, numbers of osteocytes and osteoblasts, and trabecular volume of the bones in comparison with the OVX-only group in a dose-dependent manner. No significant difference was observed between the groups in the levels of malondialdehyde and interleukin-6. Conclusion: The hydroalcoholic extract of the PG fruit prevented OVX-induced bone loss in the rats, with no proliferative effect on atrophic uteri; it should, therefore, be considered for treatment purposes.

Objective: Postmenopausal osteoporosis is characterized by increased fracture risk. However, each approved treatment has specific side effects. Therefore, foods with plant origins have increasingly attracted attention as an alternative treatment. Studies have shown that Elaeagnus angustifolia (EA) has antioxidant properties. The present study aimed to investigate the effects of EA hydroalcoholic extract on ovariectomy-induced osteoporosis in rats using stereological methods. Material and Methods: 55 female Sprague-Dawley rats were randomly assigned to control, sham operated (normal saline), ovariectomized (OVX), OVX + EA fruit extract (600 mg/kg BW/day), and OVX + estradiol benzoate (3 mg/kg BW) for 16 weeks. Blood samples were collected to measure calcium, phosphorus, and alkaline phosphatase (ALP) plasma levels. Then, specimens from tibia and fifth lumbar vertebra (L5) bones were prepared and stereological analysis was done. Results: Ovariectomy significantly decreased the calcium level and increased the ALP level in the OVX group. In spite of improvement in calcium hemostasis in groups treated with estrogen and EA fruit extract (p