Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3). METHODS: The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed. RESULTS: The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24 h was seen in the ALA + Cisplatin + Paclitaxel group. CONCLUSIONS: This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24 h, along with tumor cell adhesion.

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control + Saline), Group 2 (AT), Group 3 (AT + exercise), Group 4 (AT + sericin), and Group 5 (AT + sericin + exercise). Intratendinous sericin administration (0.8 g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1ß and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1ß were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P = 0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P = 0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

Silk protein sericin: a promising therapy for Achilles tendinopathy-evidence from an experimental rat model.

OBJECTIVE: This study investigated the efficacy of sericin in treating experimental Achilles tendinopathy (AT) in rats via the transforming growth factor-beta (TGF-ß)/mothers against decapentaplegic (Smad) pathway compared with diclofenac sodium (DS). METHOD: An AT model was induced in rats using collagenase enzyme type I and divided into 5 groups: C (control), AT (diseased control), ATS (AT treated with sericin), ATN (AT treated with DS), and ATSN (AT treated with sericin and DS). Sericin injection was given on the 3rd and 6th days by intratendinous injection (0.8 g/kg/mL), and DS was administered for 14 days by oral gavage (1.1 mg/kg/day). Serum concentrations of total oxidant-antioxidant status (TOS-TAS), TGF-ß1, decorin, Smad2, and connective tissue growth factor (CTGF) were measured. Histopathologic and immunohistochemical (IHC) studies were conducted on Achilles tendon samples. RESULTS: The TOS, oxidative stress index (OSI), TGF-ß1, Smad2, CTGF, and decorin serum concentrations were significantly higher in AT than in C and significantly lower in ATS than in AT (P<0.05). Histopathological examination revealed that irregular fibers, degeneration, and round cell nuclei were significantly elevated in AT. Spindle-shaped fibers were similar to those in C, and degeneration was reduced in ATS. TGF-ß1 and Smad2/3 expression was increased, and collagen type I alpha-1 (Col1A1) expression was decreased in AT vs. C (P=0.001). In the ATS, TGF-ß1 and Smad2/3 expression decreased, and Col1A1 expression increased. The Bonar score significantly increased in the AT group (P =0.001) and significantly decreased in the ATS group (P =0.027). CONCLUSION: Sericin shows potential efficacy in reducing oxidative stress and modulating the TGF-ß/Smad pathway in experimental AT models in rats. It may be a promising therapeutic agent for AT, warranting further clinical studies for validation. Key Points • This study revealed that sericin mitigates AT-induced damage through the TGF-ß/Smad pathway in an AT rat model. • ELISA and IHC investigations corroborated the effectiveness of sericin via the pivotal TGF-ß/Smad pathway in tissue repair. • Evidence indicates that sericin enhances collagen synthesis,shapes tendon fiber structure, and diminishes histopathological degeneration. • Sericin's antioxidant properties were reaffirmed in its AT treatment application.

Determination of the pathways of potential muscle damage and regeneration in response to acute and long-term swimming exercise in mice.

The objective of the current study was examining early and late (3, 24 h) responses to acute, chronic swimming exercise as muscle damage and regeneration in gastrocnemius-soleus muscle complexes. We also aimed to reveal the signaling pathways involved. 8-12 weeks old mice were grouped as control, exercise. Exercising groups were firstly divided into two as acute and chronic, later every group was again divided in terms of time (3, 24 h) passed from the last exercise session until exsanguination. Acute exercise groups swam 30 min, while chronic swimming groups exercised 30 min/day, 5 days/week, 6 weeks. Histological investigations were performed to determine muscle damage and regeneration. Whole-genome expression analysis was applied to total RNA samples. Microarray data was confirmed by quantitative real-time PCR. Exercising mice muscle revealed enhanced damage, leukocyte infiltration. Increments in acute and chronic 3 h groups were statistically significant. Car3, Neb, Obscn, Ttn, Igfbp5, Igfbp7, Gsk3ß, and Usp2 were down-regulated in muscles of swimming mice. The exercise-induced signaling pathways involved in muscle damage and regeneration were drawn. Our findings demonstrate that swimming induces muscle damage. Samples were obtained at 3 and 24 h following exercise, this time duration seems not sufficient for the development of myofibrillogenesis.

Do seasonal variations in ambient temperature, humidity and daylight duration affect semen parameters? A retrospective analysis over eight years.

We aimed to evaluate the possible effects of seasonal variation on semen parameters. We retrospectively analysed the data of 6,116 semen samples collected at a university hospital for eight years. The past ambient temperature, relative humidity and daylight duration records, and birth registry of the province were obtained to examine the relationship of seasonal changes in semen parameters with annual birth rates and environmental factors. The mean age was 33.03 ± 6.86 years. We found a significant difference between months for sperm concentration (p < .0001), total sperm count (p < .0001), progressively motile sperm count (p < .0001) and normal sperm morphology (p = .028). The sperm concentration and total count were significantly lower in July and August compared with December, May and June. The progressively motile sperm count in October was 23.6% less than the value of May. The temperature and temperature-humidity index were negatively correlated with semen parameters. The highest number of births was in the summer. However, no correlation was present between deliveries and the semen concentration regarding months (rs  = 0.199, p = .083). In conclusion, we observed significant seasonal and monthly differences in sperm concentration, sperm count and progressively motile sperm count. Increased ambient temperature due to seasonal changes may be a detrimental factor for semen parameters.

Contribution of Heme Oxygenase 2 to Blood Pressure Regulation in Response to Swimming Exercise and Detraining in Spontaneously Hypertensive Rats.

BACKGROUND We aimed to determine the effects of exercise followed by detraining on systolic blood pressure (SBP), heme oxygenase 2 (HO-2) expression, and carboxyhemoglobin (COHb) concentration in spontaneously hypertensive rats (SHR) to explain the role of carbon monoxide (CO) in this process. MATERIAL AND METHODS Animals were randomized into exercised and detrained groups. Corresponding sedentary rats were grouped as Time 1-2. Swimming of 60 min/5 days/week for 10 weeks was applied. Detraining rats discontinued training for an additional 5 weeks. Gene and protein expressions were determined by real-time PCR and immunohistochemistry. RESULTS Aorta HO-2 histological scores (HSCORE) of hypertensive rats were lower, while SBP was higher. Swimming caused enhancement of HO-2 immunostaining in aorta endothelium and adventitia of SHR. Exercise induced elevation of blood COHb index in SHR. Synchronous BP lowering effect of exercise was observed. HO-2 mRNA expression, HSCORE, and blood COHb index were unaltered during detraining, while SBP was still low in SHR. CONCLUSIONS CO synthesized by HO-2 at least partly plays a role in SBP regulation in the SHR- and BP-lowering effect of exercise. Regular exercise with short-term pauses may be advised to both hypertensives and individuals who are at risk.

[Investigation of the effect of ibuprofen on wound healing in experimental Staphylococcus aureus soft tissue infections]. / Deneysel Staphylococcus aureus yumusak doku enfeksiyonlarinda ibuprofenin yara iyilesmesi üzerindeki etkisinin arastirilmasi.

Soft tissue infections (STIs) occur as a result of the colonization of pathogenic bacteria upon the destruction of normal skin microbial flora and the skin integrity. Streptococci and staphylococci are the most frequent causes of bacterial STIs. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen are often used in STIs because of their analgesic and antipyretic effects. However, evidence suggests that these drugs might delay both epithelization and angiogenesis in the early phases of wound healing because of an antiproliferative effect. The aim of this study was to investigate the effect of ibuprofen on the wound healing in STIs caused by Staphylococcus aureus in immunosuppressed mice. A total of 120 female Balb/c mice were used in the study and the mice were assigned to four test groups and two control groups. The test groups were defined as follows; B (Bacteria group, n= 23), BI (Bacteria + Ibuprofen group, n= 23), BA (Bacteria + Ampicillin group, n= 23), BIA (Bacteria + Ampicillin + Ibuprofen group, n= 21); and the control groups were defined as follows; S1B2 (only immunosuppressed controls, n= 15) and S2B2 (Sham group). Immunosupression was induced with cyclophosphamide and the experimental infection was generated by subcutaneous inoculation of bacterial suspension (2 x 10(8) cfu/ml) of methicillin-sensitive S.aureus ATCC 25923 to the right hind leg. Ibuprofen was given to the mice by gastric gavage (50 mg/kg/day), and ampicillin (100 mg/kg/day) by intramuscular injection. Wound sizes that appear in the animals were measured on a daily basis. Serum and tissue (epithelial tissue, connective tissue, sebaceous glands, sweat glands) samples were obtained on the first, third and seventh days. The tissue samples were examined histopathologically by hematoxylin-eosin (HE) staining method and IL-1, IL-6, TNF-α and VEGF (Vascular Endothelial Growth Factor) levels were determined in serum samples by ELISA method. The tissue cytokine reactions were also evaluated by immunohistochemical (immunoperoxidase staining) method in tissue samples. In our study, no significant change was detected in the wound sizes of B and BI groups from the second day to the end of study period (p> 0.05). On the other hand the wound dimensions of BA and BIA groups gradually decreased and remained superficial. The average serum levels of TNF-α and IL-1 was detected low in all groups. The mean value of serum IL-6 on the first day in group B was determined to be higher compared to other groups, and when this difference was compared to groups BI and BA, and the control group, it was found statistically significant (p< 0.05). In addition, the VEGF levels which were detected low in all groups in the third day of infection increased significantly at the seventh day. The results of histopathologic and immunohistochemical studies have supported the results of ELISA and yielded similar results with serum cytokine patterns. In conclusion, our data indicated that ibuprofen has no negative effect on the wound healing in soft-tissue infections caused by S.aureus.

Effects of menopause, diabetes mellitus and steroid use on type I mesh-induced tissue reaction in a rat model.

OBJECTIVE: To evaluate the effects of menopause, use of steroids, diabetes mellitus, and site of implantation on the tissue response to type I polypropylene mesh used in pelvic reconstructive surgery. STUDY DESIGN: Forty mature female albino rats were used in the study. Inflammatory reaction and mesh-tissue detachment strength were studied in 4 different animal models; control (GI), menopause (GII), steroid+menopause (GIII), and diabetes mellitus+menopause (GIV) groups. Two pieces of 1cm×1cm type I macro porous polypropylene monofilament mesh were fixed over rectus abdominis muscle on both sides of the midline, and 0.5cm×0.5cm in size was placed into paravaginal area. Nine weeks later, implanted sling materials in the vaginal region and the right abdominal side were harvested with surrounding tissue for histopathologic examination, whereas the left sided meshes were used for the mechanical testing of detachment strength. RESULTS: The mean detachment strengths in groups were, 595±274g for GI, 410±161g for GII, 610±202g for GIII, and 457±250g for GIV (p>0.008). Inflammatory process was more intense in menopause and DM+menopause groups for both abdominal and vaginal tissues (p<0.008). There was no difference between control and steroid+menopause groups, and DM+menopause and menopause groups (p>0.008). Comparison of tissue reaction caused by meshes in abdominal and vaginal area showed more intense granulocyte infiltration in abdominal region whereas more prominent inflammation and necrosis in the vaginal site (p<0.05). CONCLUSION: The abdominal and vaginal region show differences in tissue reaction to type I mesh, and menopause was the most determining factor on the intensity of mesh induced inflammatory response.

Effect of testosterone propionate on hippocampal pyramidal neuron number in female rats.

INTRODUCTION: The hippocampus is an important region of the brain that regulates cognitive and emotional functions. In this study, we examined the impact of perinatal administration of testosterone propionate (TP) on the number of pyramidal neurons in the CA1 and CA3 regions of the hippocampi of female rats. METHODS: Five groups of rats were used in this study. Three groups of female rats were administered TP in either both the prenatal and the postnatal periods (Group 1), only the prenatal period (Group 2) or only the postnatal period (Group 3). The other two groups of rats included control females (Group 4) and control males (Group 5). The rats were sacrificed on postnatal Day 120 and their brains were analysed for hippocampal pyramidal neuron number using stereological methods. RESULTS: Control male rats (Group 5; p = 0.043) and TP-treated female rats in Groups 1 (p = 0.012) and 2 (p = 0.037), but not Group 3 (p > 0.05), had a significantly higher number of pyramidal neurons than control female rats (Group 4). The rats in Group 1 had the highest number of pyramidal neurons among the female rats. CONCLUSION: Perinatal TP treatment has an augmenting effect on the number of pyramidal neurons in the hippocampi of female rats. We also found gender-based differences in the hippocampi of male and female rats, with a higher number of pyramidal neurons seen in male rats. Continuous TP administration during the prenatal and postnatal periods is more effective than administration only in the prenatal or postnatal period.