Therapeutic potentials of the caffeine in polycystic ovary syndrome in a rat model: Via modulation of proinflammatory cytokines and antioxidant activity.

Recent studies have shown that polycystic ovary syndrome (PCOS) affects about 6% of women worldwide. It is associated with reproductive and metabolic dysfunction. Caffeine is naturally found in tea, cocoa, and coffee. It has been shown that caffeine can change hormonal profiles, stimulate ovulation, and enhance fertility. Therefore, in this study, the effects of caffeine on rats with PCOS were investigated. For this purpose, 40 female rats were divided into five groups: (1) control group (without any intervention), (2) sham group (administration of olive oil as a caffeine solvent), (3) PCOS group (injection of 2 mg of estradiol valerate for each rat), (4) caffeine group (administration of 37.5 mg/kg caffeine for each rat), and (5) PCOS + caffeine group. After 21 days of treatment, the ovaries of rats were removed and prepared for further evaluations, including hematoxylin and eosin staining, TUNEL assay, real-time PCR, and biochemical analysis. Administration of caffeine in PCOS mice considerably reduced both the volume of the ovary (P < 0.05) and follicular clusters (P < 0.01). However, superoxide dismutase and glutathione peroxidase were dramatically active in the PCOS + caffeine group compared to others (P < 0.05). Besides, caffeine treatment in PCOS mice led to Bax reduction and increased Bcl-2 expression. On the other hand, the expression of IL-6 and TNF-α in PCOS + caffeine group was high compared to other groups. We found that caffeine can reduce apoptosis and inflammation in PCOS ovaries and enhance the unpleasant symptoms of PCOS.

Toxicology of long-term and high-dose administration of methylphenidate on the kidney tissue - a histopathology and molecular study.

The present study aims to assess the influences of oral methylphenidate on kidney function and structure versus vehicle treatment in adult male rats. In this study, thirty adult male rats equally into two treatment groups divided randomly, and among them, MPH has been administered for 21 days, at doses of 20 mg/kg, and the control group has received salin. In renal, under the effect of MPH applying quantitative real-time PCR, we analyzed nephrotoxicity-related molecular pathways like autophagy, inflammation, and apoptosis. Moreover, the levels of GSH, CAT, and SOD were investigated as antioxidant enzymes. Afterward, stereological analysis in MPH-treated rats has been performed. Analysis of qPCR displayed inflammation, impaired autophagy, and enhanced apoptosis with histological changes in the kidney's tissue, also an important rise in the antioxidant enzymes' level. Besides, 20 mg/kg of MPH led to a decline in the mean of Bowman's space thickness and renal corpuscle's volume in comparison to the control rats. Collectively, our histological and molecular data implicit that in the kidney region, administrating of MPH evoked discriminative expression alterations in nephrotoxicity-associated signaling cascades, specifically autophagy, inflammation, and apoptosis paired with important damage to kidney tissue.

The ability of mouse nuclear transfer embryonic stem cells to differentiate into primordial germ cells.

Nuclear transfer embryonic stem cells (ntESCs) show stem cell characteristics such as pluripotency but cause no immunological disorders. Although ntESCs are able to differentiate into somatic cells, the ability of ntESCs to differentiate into primordial germ cells (PGCs) has not been examined. In this work, we examined the capacity of mouse ntESCs to differentiate into PGCs in vitro. ntESCs aggregated to form embryoid bodies (EB) in EB culture medium supplemented with bone morphogenetic protein 4(BMP4) as the differentiation factor. The expression level of specific PGC genes was compared at days 4 and 8 using real time PCR. Flow cytometry and immunocytochemical staining were used to detect Mvh as a specific PGC marker. ntESCs expressed particular genes related to different stages of PGC development. Flow cytometry and immunocytochemical staining confirmed the presence of Mvh protein in a small number of cells. There were significant differences between cells that differentiated into PGCs in the group treated with Bmp4 compared to non-treated cells. These findings indicate that ntESCs can differentiate into putative PGCs. Improvement of ntESC differentiation into PGCs may be a reliable means of producing mature germ cells.

Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats.

BACKGROUND: Lovastatin, as a drug of statins subgroup, has been conceptualized to have anti-inflammatory, antioxidant, and anti-apoptotic properties. Accordingly, the present study aimed to investigate the neuroprotective ramification of lovastatin on spinal cord injury (SCI). MATERIAL AND METHODS: Seventy-five female adult Wistar rats were divided into five groups (n = 15). In addition to non-treated (Control group) and laminectomy alone (Sham group), SCI animals were randomly assigned to non-treated spinal cord injury (SCI group), treated with 2 mg/kg of lovastatin (Lova 2 group), and treated with 5 mg/kg of lovastatin (Lova 5 group). At the end of the study, to evaluate the treatments, MDA, CAT, SOD, and GSH factors were evaluated biochemically, apoptosis and gliosis were assessed by immunohistochemical while measuring caspase-3 and GFAP antibodies, and inflammation was estimated by examining the expression of IL-10, TNF-α, and IL-1ß genes. The stereological method was used to appraise the total volume of the spinal cord at the site of injury, the volume of the central cavity created, and the density of neurons and glial cells in the traumatic area. In addition, Basso-Beattie-Bresnehan (BBB) and narrow beam test (NBT) were utilized to rate neurological functions. RESULTS: Our results exposed the fact that biochemical factors (except MDA), stereological parameters, and neurological functions were significantly ameliorated in both lovastatin-treated groups, especially in Lova 5 ones, compared to the SCI group. The expression of the IL-10 gene was significantly upregulated in both lovastatin-treated groups compared to the SCI group and was considerably heighten in Lova 5 group. Expression of TNF-α and IL-1ß, as well as the rate of apoptosis and GFAP positive cells significantly decreased in both lovastatin treated groups compared to the SCI group, and it was more pronounced in the Lova 5 ones. CONCLUSION: Overall, using lovastatin, especially at a dose of 5 mg/kg, has a dramatic neuroprotective impact on SCI treatment.

Caffeine modulates apoptosis, oxidative stress, and inflammation damage induced by tramadol in cerebellum of male rats.

Tramadol, an opioid used as analgesic, can induce neurotoxic effects associated to cognitive dysfunction. Moreover, caffeine has been reported to have neuroprotective effects. In this regard, we hypothesized that administration of caffeine can modulate tramadol-induced damages in cerebellum. For this study, forty male Wistar rats were divided into four groups: the control group, the tramadol group (50 mg/kg), the caffeine group (37.5 mg/kg), and the tramadol+caffeine group (50 mg/kg tramadol+37.5 mg/kg caffeine). At the end of study (day 21), after performing rotarod behavioral test, cerebellum tissue samples were removed and prepared for further evaluations including biochemical profile markers (MDA, GPx, and SOD), immunohistochemistry for Caspase-3, as well as the expression of genes involved in cellular processes such as inflammation markers (IL-1ß, HMGB1, IL-6, and TNF), apoptosis markers (Caspase-3, Caspase-8, Bax, and P21), and autophagy markers (LAMP2, ATG5, BECN1, and ATG12). Stereological evaluations were performed to determine the total volume of granular and molecular layers and white matter of cerebellum tissue and numerical density of the Purkinje cells. Our results showed that the stereological parameters, biochemical profiles (except MDA) and behavioral function were significantly higher in the tramadol+caffeine group compared to the tramadol group. Autophagy-related genes were significantly upregulated in tramadol+caffeine group compared to the tramadol group. While the expression of inflammatory and apoptosis genes, MDA level, as well as density of apoptosis cells were significantly lower in the tramadol+caffeine group compared to the tramadol group. Briefly, it can be concluded that administration of caffeine has neuroprotective effects in cerebellar damages induced by tramadol.

Report of a Novel Bilateral Variation of Sciatic and Inferior Gluteal Nerve: A Case Study.

INTRODUCTION: The sciatic nerve is the thickest nerve of the sacral plexus which innervates many muscles and vast areas of the skin of the lower limb. It leaves the pelvis via the greater sciatic foramen, emerges into the gluteal region by passing under the piriformis muscle, and descends beneath the gluteus maximus to divide into its terminal branches; the tibial and common peroneal nerve at the superior angle of the popliteal fossa. In some cases, the sciatic nerve divides into the tibial and common peroneal nerves at a higher level and one of them or both passes through or over the piriformis muscle. CASE PRESENTATION: We find an interesting bilateral variation of sciatic nerve accompanying a very thick inferior gluteal nerve on the right side and unusual route and branching of tibial and common peroneal nerves on the left side. CONCLUSION: As in conditions like intramuscular injections, gluteal surgeries, and piriformis syndrome such variations may increase the risk of injury, it is important for the medical team to be aware of them. In this paper, by reporting many variations in a cadaver, we emphasize the importance of anatomical variations, especially for surgeons and nurses.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

Effect of low-level laser therapy on healing of medial collateral ligament injuries in rats: an ultrastructural study.

OBJECTIVE: This study sought to investigate whether low-level laser therapy (LLLT) with a helium-neon (He-Ne) laser would increase fibril diameter of transected medial collateral ligament (MCL) in rats. BACKGROUND DATA: It has been shown that LLLT can increase ultimate tensile strength MCL healing. METHODS: Thirty rats received surgical transect to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with He-Ne laser and 0.01 J/cm(2) energy fluency per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy fluency (density) per day and group 3 (sham-exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while control group received neither surgery nor LLLT. Transmission electron microscope (TEM) examination was performed on days 12 and 21 after surgery and dimension and density of ligament fibrils were measured. The data were analyzed by Student t-test and Mann-Whitney tests, respectively. RESULTS: On day 12, the fibril dimension of group 2 and their density were higher than of groups 1 and 3. CONCLUSION: LLLT with He-Ne laser on incised MCL in rats could not significantly increase fibril diameter and their density in comparison with sham-exposed group.

Low-level laser therapy improves early healing of medial collateral ligament injuries in rats.

OBJECTIVE: This study sought to investigate whether or not low-level laser therapy (LLLT) with a helium-neon laser increased biomechanical parameters of transected medial collateral ligament (MCL) in rats. BACKGROUND DATA: It has been reported that LLLT can enhance tendon healing. METHODS: Thirty rats received surgical transection to their right MCL, and five were assigned as the control group. After surgery, the rats were divided into three groups: group 1 (n = 10) received LLLT with 0.01 J/cm(2) energy density per day, group 2 (n = 10) received LLLT with 1.2 J/cm(2) energy density per day, and group 3 (sham = exposed group; n = 10) received daily placebo laser with shut-down laser equipment, while the control group received neither surgery nor LLLT. Biomechanical tests were performed at 12 and 21 days after surgery. The data were analyzed by one-way analysis of variance. RESULTS: The ultimate tensile strength (UTS) of group 2 on day 12 was significantly higher than that of groups 1 and 3. Furthermore, the UTS and energy absorption of the control (uninjured) group were significantly higher than those of the other groups. CONCLUSIONS: LLLT with a helium-neon laser is effective for the early improvement of the ultimate tensile strength of medial collateral ligament injuries.