The protective effects of hesperidin pretreatment on kidney and remote organs against renal ischemia-reperfusion injury.

OBJECTIVE: As an antioxidant and anti-inflammatory agent, Hesperidin was investigated to prove whether it prevents damage to the kidney and lung tissues of rats undergoing renal ischemia-reperfusion injury. MATERIALS AND METHODS: Four groups of rats were set, including eight subjects each as Group 1 (control), Group 2-RIR (renal ischemia reperfusion), Groups 3 and 4 as pretreatment groups (50 HES, 100 HES). RESULTS: According to our results, Hesperidin pretreatment improved the biochemical and histopathological parameters in kidney and lung tissues of rats with ischemia-reperfusion injury. Besides, a 100 mg/kg dose of Hesperidin was found to be more beneficial to the rats than 50 mg/kg. CONCLUSIONS: The study suggests that Hesperidin is protective against renal and lung tissues of rats that underwent ischemia-reperfusion injury.

The relationship between hemoglobin-RDW ratio and clinical outcomes in patients with advanced pancreas cancer.

OBJECTIVE: The prognostic significance of hemoglobin (HGB) -red cell distribution width (RDW) ratio (HRR) has been indicated in various cancer types. However, its clinical significance in patients with metastatic pancreas cancer (MPC) is unknown. In this study, we aimed to investigate the prognostic importance of pre-treatment HRR in patients with metastatic pancreas cancer. PATIENTS AND METHODS: MPC patients (≥18 years of age) who received at least one course of chemotherapy between January 2001 and January 2021, were evaluated retrospectively in terms of pre-treatment HRR values. RESULTS: Of 111 patients, the mean HRR value was 0.84, and the patients were divided into low HRR and high HRR groups. The median follow-up was 8.7 months (95% CI 1.8-51.6). The median duration of first-line treatment was 4.4 months (95% CI 0.5-31.3). The median overall survival (OS) was 7.6 months (95% CI 3.4-11.8) in the low HRR group and 8.7 months (95% CI 5.7-11.8 months) in the high HRR group (p=0.276) (Figure 1). The median progression-free survival (PFS) was 4.2 months (95% CI 2.7-5.6 months) in the low HRR group and 5.1 months (95% CI 2.8-7.4 months) in the high HRR group (p=0.044) It was found that high HRR decreased progression event in both univariate (HR 0.67, 95% CI 0.45-0.99, p=0.046) and multivariate (HR 0.62, 95% CI 0.42-0.93, p=0.022) analysis. CONCLUSIONS: The present study emphasized that low HRR was a poor prognostic factor for PFS in patients with MPC. There was no statistically significant difference between the HRR groups regarding OS. This is the first study evaluating the prognostic significance of HRR in MPC.

Factors affecting prognosis and treatment strategies in metastatic soft tissue sarcomas: twenty years of experience.

OBJECTIVE: In this study, we aimed to reveal the general clinicopathological features, treatment features, and factors that could predict overall survival in metastatic soft tissue sarcomas, a very rare and heterogeneous disease group. PATIENTS AND METHODS: This study was a retrospective cohort study. Patients monitored with metastatic soft tissue sarcoma between January 2001 and January 2021 were evaluated retrospectively. Patients aged 18 years and over, histopathologically diagnosed with metastatic STS, and unsuitable for operations, such as local curative surgery or metastasectomy, were included in the study. RESULTS: A total of 179 patients in the metastatic stage and monitored in our center were included in the study. The median follow-up period was 8.4 months (IQR, 3.4-14.4). 58 (32.4%) patients were de-novo metastatic, and 121 (67.6%) patients developed metastasis later. The median age was 53.2 (Range: 18.8-87.6 years), and 101 (56.4%) patients were male. The most common primary location was the lower extremity (87) (48.6%). The most common histological subtypes were synovial sarcoma (38) (21.2%), pleomorphic sarcoma (37) (20.7%), and liposarcoma (26) (14.5%). The majority were grade 3 tumors (n=131, 73.2%). Having ECOG PS 2-3 (HR=2.829, 95% CI 1,667-4.800, p<0.001), having tumor grade as 3 (HR=1.748, 95% CI 1.150-2.656, p<0.009), receiving palliative chemotherapy (HR=0.294, 95% CI 0.144-0.600, p<0.001), and receiving two or more lines of chemotherapy among those palliative receivers (HR=2.505 95% CI 1.696-3.700, p<0.001) were independent predictive factors of mortality. CONCLUSIONS: Survival in metastatic soft tissue sarcoma is better in patients with good ECOG performance status, low tumor grades, and who have received palliative chemotherapy. Receiving more than one line of palliative systemic treatment for progressive disease improves survival.

Treatment options after regorafenib failure in metastatic colorectal cancer.

OBJECTIVE: In the treatment of metastatic colorectal cancer (mCRC), there is a need for a treatment option in patients who have received regorafenib (RGR) therapy and progressed, especially in patients fit enough to receive a new therapy. We aimed to compare the role of rechallenge chemotherapy (RCH CTx) with best supportive care (BSC) in mCRC patients after standard CTx and subsequent RGR treatment in terms of survival benefit. PATIENTS AND METHODS: Patients with progressive mCRC who received at least one month of subsequent RGR therapy after standard CTx treatments were included in the study. Patients were divided into two groups: receiving RCH CTx or BSC (without antitumoural therapy) after RGR failure. There were 26 patients in the RCH CTx group and 30 patients in the BSC group. The RCH CTx and BSC groups were compared for demographic and clinical features, laboratory parameters, and survival rates. RESULTS: After the RGR failure, the median overall survival (OS) for the RCH CTx (n = 26) and BSC (n = 30) groups were 7.5 (95% CI, 6.3-8.7) months and 1.2 (95% CI, 0.9-1.5) months, respectively (p < 0.001). The median OS was 7.5 (95% CI, 6.3-8.7) months for the RCH CTx (n = 26) and 1.4 (95% CI, 0.3-2.4) months for the BSC (n = 14) groups when only the patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2 at progression with RGR treatment were compared, respectively (p < 0.001). CONCLUSIONS: After the RGR failure, mCRC patients, especially those with a better ECOG-PS (≤ 2) and adequate organ function, should be considered candidates for RCH CTx instead of BSC.

Noise Stress-Induced Changes in mRNA Levels of Corticotropin-Releasing Hormone Family Molecules and Glucocorticoid Receptors in the Rat Brain.

Noise is a widespread stress resource that may lead to detrimental effects on the health. However, the molecular basis of the stress response caused by noise remains elusive. We have studied the effects of acute and chronic noise stress on stress-related molecules in the hypothalamus and hippocampus and also corticosterone responses. Sprague Dawley rats were randomized into control, acute and chronic noise stress groups. While the chronic noise stress group animals were exposed to 100 dB white noise for 4 h/a day during 30 days, the acute noise stress group of animals was exposed to the same level of stress once for 4 h. The expression profiles of corticotropin releasing hormone (CRH), CRH1, CRH2 receptors and glucocorticoid receptor (GR) mRNAs were analysed by RT-PCR. Chronic noise stress upregulated CRH mRNA levels in the hypothalamus. Both acute and chronic noise increased CRH-R1 mRNA in the hypothalamus but decreased it in the hippocampus. GR mRNA levels were decreased by chronic noise stress in the hippocampus. The present results suggest that while corticosterone responses have habituated to continuous noise stress, the involvement of CRH family molecules and glucocorticoid receptors in the noise stress responses are different and structure specific.

Effects of Saccharomyces cerevisiae extract on haematological parameters, immune function and the antioxidant defence system in breeder hens fed aflatoxin contaminated diets.

The study was conducted to investigate the efficacy of Saccharomyces cerevisiae extract (SC) on haematological parameters, immune function, and the antioxidant defence system in breeder hens fed a diet contaminated with low level aflatoxin (AF). Forty-eight Ross 308 breeder hens were fed on diets containing AF (0 or 100 µg/kg) and SC (0 or 1 g/kg) in a 2 × 2 factorial arrangement. Red blood cell (RBC), white blood cell (WBC), and platelet counts, differential leucocyte counts, blood CD3+, CD4+, CD8+ and CD5+ T cell ratios, phagocytic activity and oxidative burst of heterophils, plasma and liver catalase activity, and malondialdehyde (MDA) and ascorbic acid concentrations were measured. 3. Plasma and liver MDA concentrations increased (P < 0·05), liver catalase activity decreased (P < 0·05) and total WBC count tended to decrease (P = 0·082) in hens fed the contaminated diet. WBC count, monocyte percentage, phagocytic activity and oxidative burst of heterophils increased (P < 0·05), and plasma MDA concentration tended to decrease (P = 0.088) in SC extract supplemented hens. There was a significant interaction between AF and SC on heterophil, lymphocyte, CD5+ cell percentages, and plasma catalase activity. Blood heterophil percentage decreased but lymphocyte percentage increased in hens fed on the AF contaminated diet without SC supplementation. SC supplementation counteracted the negative effect of AF on heterophils and lymphocytes. The CD5+ cell percentage decreased in unsupplemented hens fed the AF contaminated diet and this negative effect was minimised in SC supplemented hens. Plasma catalase activity increased in SC supplemented hens fed the uncontaminated diet whereas the effect of SC decreased in hens fed the AF contaminated diet. 4. The SC reduced some of the some adverse effects of AF, and improved functions of the non-specific immune system. Therefore, the SC extract which has been used for improving productive performance in birds and mammals may also be useful for modulating some of the effects of a low level, chronic dosage of AF.

The effects of Saccharomyces cerevisiae extract on the weight of some organs, liver, and pancreatic digestive enzyme activity in breeder hens fed diets contaminated with aflatoxins.

The effects of the Saccharomyces cerevisiae extract on some organ, liver, and pancreatic digestive enzymes in breeder hens fed on aflatoxin (AF)-contaminated feed were investigated. Forty-eight 58-wk-old Ross 308 breeder hens were used. The hens were fed diets containing 0 or 100 µg of AF/kg and 0 or 1 g of S. cerevisiae/kg in a 2×2 factorial arrangement of treatments. Although serum alkaline phosphatase levels were significantly higher, serum alkaline aminotransferase (P=0.068) and gamma-glutamyltransferase (P=0.067) levels tended to increase (P<0.05) in hens fed the AF-contaminated diet than those of hens fed the uncontaminated diet. Both AF and S. cerevisiae extract increased (P<0.001) pancreatic amylase activity, but the effect was not additive, resulting in an AF×S. cerevisiae extract interaction (P<0.001). α-Amylase activity in duodenum was lower (P<0.001) in hens fed the AF-contaminated diet. Duodenum α-amylase activity was higher (P=0.024), but jejunum α-amylase activity was lower in S. cerevisiae extract-supplemented hens than that of nonsupplemented hens. There was a significant interaction between AF and S. cerevisiae extract on pancreatic and duodenal lipase activity. Pancreatic lipase activity decreased in hens fed the AF-contaminated diet. However, S. cerevisiae supplementation extract minimized this effect of AF on pancreatic lipase activity. Duodenal lipase activity was decreased in hens fed the AF-contaminated diet without S. cerevisiae extract supplementation. However, there were not any significant differences between hens fed the AF-contaminated diet and hens fed the uncontaminated diet after S. cerevisiae extract supplementation. Pancreatic trypsin activity was higher (P=0.044) in hens fed the AF-contaminated diet than that of hens fed the uncontaminated diet. There was a significant interaction between AF and S. cerevisiae extract on pancreatic chymotrypsin activity. It was increased in hens fed the AF-contaminated diet without S. cerevisiae extract supplementation. However, S. cerevisiae extract supplementation counteracted this negative effect of AF on pancreatic chymotrypsin activity. The treatments did not result in any change in duodenal chymotrypsin activity, but S. cerevisiae supplementation decreased (P<0.05) jejunal chymotrypsin activity. In conclusion, our results showed that addition of 1 g/kg of S. cerevisiae extract reduces the toxic effects of AF on pancreatic lipase and chymotrypsin activity. Therefore, it may be useful to supplement feedstuff with S. cerevisiae extract to reduce the effects of AF in laying breeder hens.