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OBJECTIVE: In this study, we aimed to investigate the effect of type of fluid (Normal Saline solution: NSS or Lactated Ringer's solution: LRS) to be selected in fluid replacement in acute pancreatitis (AP) treatment on disease severity. SUBJECTS AND METHODS: This study is a prospective, single-center study. Patients diagnosed with acute pancreatitis in emergency service were included in the study and randomized to receive LRS or NSS. The severity of AP was determined regarding Revised Atlanta Classification. C-reactive protein (CRP) levels and serum pH and bicarbonate (HCO3) levels were measured to evaluate the systemic inflammatory response and to detect changes in acid-base balance, respectively. RESULTS: Sixty-five and seventy-seven patients receiving NSS and LRS, respectively, were analyzed. Eighty-nine (67.4%) and 43 (32.6%) patients were with mild and moderate Ap, respectively; however, there was no patient with severe AP. The frequency of moderate AP was significantly lower in the LRS group than the NSS group in terms of the severity of AP (p=0.011). Subjects that were randomized to receive LRS had lower CRP levels when compared to the participants in the NSS treatment arm 48 hours after resuscitation (p=0.010). In addition to these results, serum pH and HCO3 level in patients resuscitated with NSS reduced in comparison to LRS (p<0.001). CONCLUSIONS: Resuscitation with LRS is associated with decreased severity of AP in patients with AP. It may derive from how it causes lower CRP levels. [ABSTRACT FROM AUTHOR]

In this study, the energy view of an oven of a 70-oven coke battery in an iron and steel plant was evaluated based on operating parameters and recommendations for improving efficiency were made. A mass and energy balance per coking period (p) was created for a coke oven. It was found that during each coking period, 51.2% of the energy input was used as coking heat. It is predicted that approximately 6.91% of the input energy can be recovered from flue gas into the combustion air. By recovering the heat from the flue gas into the combustion air, the efficiency of the coke oven can be increased to 58.11%. The heat of the coke oven gas can be recovered and converted into usable form, which accounts for 6.53% of the total energy input. With the dry quenching process, it is possible to recover around 24% of the energy used from coke. Improved oven insulation, heat recovery from coke and flue gases, and the dry quenching process can recover energy worth more than 25.19 GJ/p. The energy efficiency of the furnace was predicted to rise to 82.11% with coke dry quenching and to more than 88.64% with coke gas heat recovery and insulation upgrades. The potential economic savings are $2578, equivalent to a reduction in CO₂ emissions of 2.45 tons per coking period. The financial equivalent of emissions reductions from carbon trading could be $233 per coking period. Through the processes of dry coke quenching, coke gas (CG), and flue gas heat recovery and thermal insulation improvements of the coke battery, the total amount of recoverable energy can exceed 617,294 GJ/year.

In this study, we have investigated the effects of suberoylanilide hydroxamic acid (SAHA) against chronic myeloid leukemia (CML) cells in combination studies with methotrexate (MTX), which is a dihydrofolate reductase inhibitor used in combination therapy with other agents or alone. Combination of synergistic ratios of MTX and SAHA led to apoptotic cell death of CML cells via PARP cleavage, cytochrome c release and ROS increase in vitro. We suggest that combination of MTX and SAHA may minimize the toxicity and side effects of SAHA treatment, thus providing lower amounts of each drug in CML treatment. [ABSTRACT FROM AUTHOR]

Flavonoids have chemo-preventive and chemotherapeutic properties against different human cancers including chronic myeloid leukemia. Quercetin and curcumin are two polyphenols with potential anti-carcinogenic and pro-apoptotic properties. We have previously demonstrated the synergistic protective effect of quercetin and curcumin on chronic myeloid leukemia cells (K562) cells. Anti-proliferative and apoptotic effects of these polyphenols were examined by apoptosis and cell viability assays. Oxidative status of the cells was analyzed by determining the level of reactive oxygen species, mitochondrial permeability and intracellular glutathione. Obtained data showed that quercetin and curcumin had beneficial and synergistic effects on K562 cells. On the basis of the above-mentioned data, herein we aimed to clarify signaling pathways involved in synergistic combination of quercetin and curcumin on K562 cells. Normal peripheral blood mononuclear cell line was used as controls. The mRNA and protein expressions of the signaling pathways were detected by Human Signal Transduction Pathway Finder-RT2 PCR Array system and Western blotting, respectively. The results of PCR array were evaluated by DAVID v6.8 and database for KEGG pathways. Our data revealed that synergistic combination of curcumin quercetin was effective on genes that were particularly related to P53, NF and TGF. We believe that our findings will lead to new research in this area and will contribute to the chronic myeloid leukemia treatment protocols.

In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.

Background: Anxiety is an adaptive response to potentially threatening conditions. Excessive and uncontrolled anxiety responses become nonadaptive and cause anxiety disorders. To better understand the anxiety-modulating effects of Mg sulfate, behavioral test batteries in the assessment of anxiety and learning and memory functions were performed simultaneously over a time period. This study also examines the effects of Mg sulfate compared to diazepam, an anxiolytic drug with amnestic effects on anxiety-like behavior, as well as possible oxidative-nitrosative stress and hippocampal changes in male rats exposed to predator odor., Methods: Young adult Sprague-Dawley male rats were used. The rats were assessed using a comprehensive neurobehavioral test battery consisting of novel object recognition, open field, and successive alleys tasks. Anxiety was induced by cat odor, and diazepam and Mg were used as study drugs. Of the frontal cortex and hippocampus, the state of total oxidant and antioxidant and NO levels and histological examination of hippocampal CA1, CA2, CA3, and DG regions were performed., Results: Diazepam- and Mg-treated rats showed an improvement in anxiety-related behavior to predator odors. Furthermore, Mg treatment alleviated some of the increasing oxidative stress in the frontal cortex and hippocampus of rats, while diazepam treatment in particular enhanced hippocampal oxidant and antioxidant activity. In addition, brain NO increase induced by animal odor exposure or diazepam treatment was ameliorated by Mg administration., Conclusions: Overall, our work suggests that Mg had a partial anxiolytic effect on anxiety-like behaviors, although not as much as diazepam, and this effect varied depending on the dose. Mg treatment might counteract increased oxidative stress and elevated NO levels in the brain.

Recent investigations indicate that tannic acid is associated with a decrease in oxidative damage. Growing evidence supports the protective effects of tannic acid on the central nervous system (CNS). However, uncertainties persist regarding its influence on hydrogen peroxide (H 2 O 2 )-triggered oxidative impairment in nerve cells and its interaction with apoptosis. Hence, the objective of this work was to examine the neuroprotective impact of tannic acid on SH-SY5Y cell impairment following H 2 O 2 -induced oxidative stress, particularly concerning apoptotic pathways. The control group received no treatment, while the H 2 O 2 group underwent treatment with 0.5 mM H 2 O 2 for a duration of 24 h. The tannic acid group received treatment with different concentrations of tannic acid for a duration of 24 h. Meanwhile, the tannic acid + H 2 O 2 group underwent pre-treatment with tannic acid for one hour and was subsequently subjected to 0.5 mM H 2 O 2 for one day. Within the tannic acid + H 2 O 2 group, the cell viability in SH-SY5Y cells was notably enhanced by tannic acid at concentrations of 2.5, 5, and 10 μM. It also resulted in a considerable rise in TAS (Total Antioxidant Status) levels and a concurrent decline in TOS (Total Oxidant Status) levels, serving as indicators of reduced oxidative stress. Additionally, tannic acid treatment resulted in decreased levels of apoptotic markers (Bax, cleaved PARP, and cleaved caspase 3) and oxidative DNA damage marker (8-oxo-dG), while increasing the anti-apoptotic marker Bcl-2. The findings from flow cytometry also revealed a significant reduction in the apoptosis rate following pretreatment with tannic acid. In summary, tannic acid demonstrates protective effects on SH-SY5Y cells in the face of H 2 O 2 -triggered oxidative damage by suppressing both oxidative stress and apoptosis. Nevertheless, additional research is warranted to assess the neuroprotective potential of tannic acid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye., Method: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed., Results: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p  = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p  = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p  = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p  = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p  = 0.009) were found to be significant regarding remission., Conclusion: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

In the present work, the mechanism of anticancer activity of some pyrrolopyrimidine derivatives was evaluated. Compounds 5 and 8 exhibiting significant antiproliferative activity against HT-29 cells with IC 50 values of 4.17 μM and 2.96, arrested the cells at the G2/M phase and significantly induced apoptosis. The apoptotic potential of the compounds has been verified via ELISA assay, which resulted in increased BAX, PUMA, BIM, and cleaved caspase 3 expression and decreased BCL-XL and MCL-1 protein levels in HT-29 cells. Moreover, the immunofluorescence technique showing that compounds 5 and 8-treatment reduced Ki67 immunolocalization and increased the caspase 3 and p53 immunolocalization confirmed the apoptotic activity. While treatment of HT-29 cells to compounds 5 and 8 inhibited Akt and ERK1/2, there are no alterations in JNK and p38 signaling pathways. According to molecular docking results, compounds 5 and 8 occupied the active site of Akt kinase and showed important hydrogen bonding interactions with key amino acids. Also, siRNA-mediated depletion of BIM, PUMA, and BAX/BAK expression decreased apoptotic response in HT-29 cells upon exposure to compound 5 and compound 8. Compounds 5 and 8 trigger the activation of mitochondrial apoptosis in HT-29 cells. Additionally, we found that proapoptotic BH3-only proteins BIM and PUMA are required for the full engagement of mitochondrial apoptosis signaling. However, p53 was dispensable for compound 5- or compound 8-induced apoptosis in HT-29 cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

The PI3K pathway plays a crucial role in tumor cell proliferation across various cancers, including colon cancer, making it a promising treatment target. This study aims to investigate the antiproliferative activity of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor, on colon cancer and elucidate the underlying mechanisms. HT-29 colon cancer cells were treated with varying doses of ETP 45658 and its cytotoxic effect assessed using the XTT cell viability assay.ELISA was also used to measure TAS, TOS, Bax, BCL-2, cleaved caspase 3, cleaved PARP, and 8-oxo-dG levels. Flow cytometry was performed to investigate apoptosis, cell cycle, caspase 3/7 activity, and mitochondrial membrane potential. Additionally, following the administration of DAPI (4,6-diamidino-2-phenylindole) dye, the cells were visualized using an immunofluorescence microscope. It was observed that ETP-45658 exerted a dose-dependent and statistically significant antiproliferative effect on HT-29 colon cancer cells. Further investigations using the IC 50 dose showed that ETP-45658 decreased TAS levels and increased TOS levels and revealed that it upregulated apoptotic proteins while downregulating anti-apoptotic proteins. Our findings also showed that it increased Annexin V binding, arrested the cell cycle at G0/G1 phase, induced caspase 3/7 activity, impaired mitochondrial membrane potential, and ultimately triggered apoptosis in HT-29 cells. ETP-45658 shows promise against colon cancer by inducing cell death, and oxidative stress, and arresting the cell cycle. Targeting the PI3K/AKT/mTOR pathway with ETP-45658 offers exciting potential for colon cancer treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: With increased fluid intake and tolvaptan treatment, the growth rate of cysts can be theoretically decelerated in autosomal polycystic kidney disease. In this prospective study, it was planned to evaluate thirst sensation in these patients and the parameters affecting its intensity., Methods: Forty-one ADPKD patients on tolvaptan and 40 ADPKD patients not on tolvaptan as the control group were evaluated for thirst distress sensation and intensity. The feeling of thirst and the discomfort caused by excessive fluid intake was assessed with Thirst Distress Scale-HF 12 questions (60/12). Thirst intensity was evaluated with a 100 mm visual scale., Results: Of the whole group, 35.8% (29) were males, and 64.2% (52) were females. The mean age of the tolvaptan group was 39.17 ± 9.35 years and for the control group, it was 41.95 ± 12.29 years. There was a negative correlation between the thirst distress score of the patients and an increase in creatinine level after a year of tolvaptan treatment (r = - 0.335, p = 0.035). The patients not taking thiazide had higher thirst intensity scores (p = 0.004). There was no impact of tolvaptan dosage, total kidney volume, serum sodium, urinary osmolarity or eGFR on thirst distress and thirst intensity scores., Discussion/conclusion: Only thiazide co-treatment had a positive impact on thirst distress and intensity when given tolvaptan. Thirst Distress Scale for ADPKD patients can be used to classify patients before and during tolvaptan treatment., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Polo-like kinase 1 (PLK1) is crucial in regulating cell division and has been shown to have an oncogenic function in several cancers. Since PLK1 overexpression is closely related to tumorigenesis and has been correlated with poor clinical outcomes, specific inhibition of PLK1 in cancer cells is a promising approach for developing new anticancer drugs. In this context, the aim of the present study was to evaluated the potential cytotoxic effects of GSK461364A, a competitive inhibitor for PLK1, in gastric cancer cell line SNU-1 cells and explored its cytotoxic mechanism. The cells were exposed to GSK461364A at different concentrations ranging from 1 to 40 μM for 24 h, and it showed considerable cytotoxicity with an IC 50 value of 4.34 μM. The treatment of SNU-1 cells with GSK461364A results in cell cycle arrest at the G2/M phase, decreased mitochondrial membrane potential, and increased apoptosis as indicated by Annexin V binding assay. In addition, GSK461364A treatment significantly increased the total oxidant (TOS) level, a signal of oxidative stress, and increased cleaved PARP and 8-oxo-dG levels as an indicator of DNA damage. ELISA experiments evaluating Bax, BCL-2, and cleaved caspase 3 also confirmed the apoptotic effect of GSK461364A. Current findings suggest that GSK461364A may be a chemotherapeutic agent in patients with gastric cancer. Nevertheless, more research is needed to evaluate GSK461364A as a cancer treatment drug., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Cancer cells restrain apoptotic and senescence pathways through intracellular heat shock protein 70 (Hsp 70). These cells aid stimulus-independent growth, and their higher metabolism rate requires Hsps. Hsps compensate abnormally increased substrate protein folding rate of cancer cells., Objective: Misfolding of substrate proteins especially signaling substrate proteins, may not function properly. Therefore, Hsp70 folds these substrate proteins into their native-fully functional states, and this mode of action helps cancer cell survival., Methods: Targeting Hsps is promising cancer therapy, and in this study, 6,8,9-trisubstituted purine derivatives were designed and synthesized to inhibit Hsp70 and drive cancer cells to apoptosis. Further, oncogenic stimuli through inhibitors can induce an irreversible senescent state and senescence is a barrier to transformation., Results: Hsp70 helps cancer cells to bypass the cellular senescence program, however, binding of N6-(4- isopropylaniline) analogue (7) depletes Hsp70 function as evidenced by aggregation assay and Hsp70 depletion induces senescence pathway., Conclusion: The purine-based inhibitor-compound 7 effectively inhibits MCF-7 cell line. Moreover, the therapeutic potential with regard to the senescence-associated secretory phenotype has complementary action. Dual action of the inhibitor not only drives the cells to apoptosis but also force the cells to be in the senescence state and provides promising results specially for luminal A type breast cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats., Methods: In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method., Results: The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area., Discussion: 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.

A new series of thiosemicarbazone derivatives (1-11) were prepared from various aldehydes and isocyanates with high yields and practical methods. The structures of these compounds were elucidated by Fourier transform infrared, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR spectroscopic methods and elemental analysis. Cytotoxic effects of target compounds were determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay and compound 1 showed significant cytotoxic activity against both MCF-7 and MDA-MB-231 cells, with half-maximal inhibitory concentration values of 2.97 μM and 6.57 μM, respectively. Moreover, in this study, the anticholinergic and antidiabetic potentials of these compounds were investigated. To this aim, the effect of the newly synthesized thiosemicarbazone derivatives on the activities of acetylcholinesterase (AChE) and αglycosidase (α-Gly) was evaluated spectrophotometrically. The title compounds demonstrated high inhibitory activities compared to standard inhibitors with K i values in the range of 122.15-333.61 nM for α-Gly (K i value for standard inhibitor = 75.48 nM), 1.93-12.36 nM for AChE (K i value for standard inhibitor = 17.45 nM). Antiproliferative activity and enzyme inhibition at the molecular level were performed molecular docking studies for thiosemicarbazone derivatives. 1M17, 5FI2, and 4EY6, 4J5T target proteins with protein data bank identification with (1-11) compounds were docked for anticancer and enzyme inhibition, respectively., (© 2022 Wiley Periodicals LLC.)

Recent studies have shown that angiotensin-converting enzyme (ACE) inhibitors have reduced oxidative damage in the central nervous system (CNS). Accumulating evidence have also demonstrated that captopril, an ACE inhibitor, has protective effects on the CNS. However, its effects on hydrogen peroxide (H 2 O 2 )-induced oxidative damage in glial cells and interaction with the inflammatory system are still uncertain. Therefore, this study was aimed to investigate the protective effect of captopril on glial cell damage after H 2 O 2 -induced oxidative stress involved in the inflammatory and apoptotic pathways. The control group was without any treatment, and the H 2 O 2 group was treated with 0.5 mM H 2 O 2 for 24 h. The captopril group was treated with various concentrations of captopril for 24 h. The captopril + H 2 O 2 group was pre-treated with captopril for 1 h and then exposed to 0.5 mM H 2 O 2 for 24 h. In the captopril + H 2 O 2 group, captopril at all concentrations significantly increased the cell viability in C6 cells. It also significantly increased the TAS and decreased the TOS levels which are an indicator of oxidative stress. Moreover, captopril significantly reduced the inflammation markers including NF-kB, IL-1 β, COX-1, and COX-2 levels. Flow cytometry results also exhibited that captopril pretreatment significantly decreased the apoptosis rate. Besides, captopril significantly reduced apoptotic Bax and raised anti-apoptotic Bcl-2 protein levels. In conclusion, captopril has protective effects on C6 cells after H 2 O 2 -induced oxidative damage by inhibiting oxidative stress, inflammation, and apoptosis. However, further studies need to be conducted to evaluate the potential of captopril as a neuroprotective agent., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent evidence has shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its effect and mechanisms on glutamate-induced cytotoxicity are still unclear. The current experiment was designed to examine the effect of sCT on glutamate-induced cytotoxicity in C6 cells, involving the inflammatory and nitric oxide stress pathways. The study used the C6 glioma cell line. Four cell groups were prepared to evaluate the effect of sCT on glutamate-induced cytotoxicity. The control group was without any treatment. Cells in the glutamate group were treated with 10 mM glutamate for 24 h. Cells in the sCT group were treated with various concentrations (3, 6, 12, 25, and 50 µg/mL) of sCT for 24 h. Cells in the sCT + glutamate group were pre-treated with various concentrations of sCT for 1 h and then exposed to glutamate for 24 h. The cell viability was evaluated with an XTT assay. Nuclear factor kappa b (NF-kB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), caspase-3, and caspase-9 levels in the cells were measured by ELISA kits. Apoptosis was detected by flow cytometry method. sCT at all concentrations significantly improved the cell viability in C6 cells after glutamate-induced cytotoxicity (p < 0.001). Moreover, sCT significantly reduced the levels of NF-kB (p < 0.001), TNF-α, and IL-6 levels (p < 0.001). sCT also decreased nNOS, NO, and cGMP levels (P < 0.001). Furthermore, it decreased the apoptosis rate and increased the live-cell rate in the flow cytometry (P < 0.001). In conclusion, sCT has protective effects on glutamate-induced cytotoxicity in C6 glial cells by inhibiting inflammatory and nitric oxide pathways. sCT could be a useful supportive agent for people with neurodegenerative symptoms., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This work examined the cytotoxic effects of colchicine on PC3 cells and elucidated the possible underlying mechanisms of its cytotoxicity. The cells were exposed to colchicine at different concentrations ranging from 1 to 100 ng/mL for 24 h, and it showed considerable cytotoxicity with an IC 50 value of 22.99 ng/mL. Mechanistic studies also exhibited that colchicine treatment results in cell cycle arrest at the G2/M phase as well as decreased mitochondrial membrane potential and increased early and late apoptotic cells. The apoptotic and DNA-damaging effects of colchicine have also been verified by fluorescence imaging and ELISA experiments, and they revealed that while colchicine treatment significantly modulated expression as increases in Bax, cleaved caspase 3, cleaved PARP, and 8-hydroxy-desoxyguanosine levels and as a decrease of BCL-2 protein expression. Besides, colchicine treatment significantly increased the total oxidant (TOS) level, which is a signal of oxidative stress and potential cause of DNA damage. Finally, the results of quantitative real-time PCR experiments demonstrated that colchicine treatment concentration-dependently suppressed MMP-9 mRNA expression. Overall, colchicine provides meaningful cytotoxicity on PC3 cells due to induced oxidative stress, reduced mitochondrial membrane potential, increased DNA damage, and finally increased apoptosis in PC3 cells. Nevertheless, further research needs to be conducted to assess the potential of colchicine as an anticancer drug for the treatment of prostate cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Accumulating evidences indicate that thiamine plays a vital role in the nervous system. However, questions exist as to how it causes epilepsy, neuronal damage, and antiepileptic mechanisms. The study looked at how the thiamine supplement impacted pentylenetetrazole (PTZ)-induced seizures in rats and pentylenetetrazole-induced neurotoxicity in the SH-SY5Y cell line. We used twenty-four male rats and they were randomly divided into 4 groups as control, saline (1 mL/kg/day serum physiologic) + PTZ, thiamine (50 mg/kg/day) + PTZ, and thiamine (50 mg/kg/day) for 10 days. PTZ (45 mg/kg) was given to activate the seizure on day 10. Memory efficiency was measured by using passive avoidance. The brain levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) were analyzed by using ELISA kits. SH-SY5Y cells were treated with/without thiamine for 1 h, followed by PTZ (30 μm) at a medium level to trigger neurotoxicity. Cell viability, total antioxidant status, total oxidant status, and apoptosis were assayed in the SH-SY5Y cells. Thiamine delayed the initiation of epileptic seizures and increased memory damage. In addition, 8-OHdG, caspase-3, NO, and cGMP levels were significantly reduced in the brain and prevented pentylenetetrazole-induced neurotoxicity, apoptosis, enhanced antioxidant, and reduced oxidant in SH-SY5Y cells. Thiamine dramatically altered seizures, memory loss, oxidative stress, and apoptosis. Thiamine has a preventative effect on PTZ-induced seizures in rats and PTZ-induced neurotoxicity in SH-SY5Y neuroblastoma cells. It could prevent oxidative stress and signaling of NO/cGMP. Thiamine supplement could be used as an additional therapeutic agent in epilepsy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country., Methods: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded., Results: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001)., Conclusion: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.

Polo-like kinase 1 (PLK1) is a prominent mediatory player during the cell cycle, mitosis, and cytokinesis in eukaryotic cells. Besides its physiological roles, PLK1 expression is upregulated in a wide range of human malignant tumors and its overexpression worsens prognosis, therefore, specific inhibition of PLK1 in tumor cells is a fascinating approach for the development of novel chemotherapeutics. The present study elucidated the potential cytotoxic effects of a PLK1 inhibitor, GSK461364A, in five cancer cell lines including Raji, K562, PC3, MCF-7, MDA-MB-231, along with noncancerous L929 cells by XTT assay. The cells were treated for 24 h with GSK461364A at different concentrations ranged between 0.5 and 40 μM and significant cytotoxicity was observed in all treated groups with the IC 50 values between 2.36 and 4.08 μM. GSK461364A was also found to be safer with lower cytotoxicity against L929 cells and the IC 50 value was found to be greater than 40 μM. Raji cells were identified as the most sensitive cell line against GSK461364A with the lowest IC 50 values, hence it was selected for further studies to evaluate the underlying mechanism of cytotoxic activity. The treatment of Raji cells with GSK461364A caused a cell cycle arrest at the G2/M phase, also altered TOS, which is an indicator of oxidative stress, and DNA damage response, significantly. The Annexin V binding assay revealed that GSK461364A treatment significantly increased in the percentage of early and late apoptotic cells. Fluorescence imaging also showed that GSK461364A treatment significantly induced apoptosis of Raji cells. The apoptotic effect of the compound has also been confirmed by increased expressions of Bax and cleaved caspase 3 and along with the decreased expression of BCL-2. The results demonstrated that GSK461364A induced anticancer effects which was mainly promoted by cell cycle arrest, oxidative stress, DNA damage, and finally apoptosis in Burkitt's lymphoma cells. Taken together, the present results emphasized that GSK461364A could be a useful therapeutic agent in patients with Burkitt's lymphoma. However, further studies are required to consolidate the anticancer activity of this promising compound., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Epilepsy is one of the most common neurological disorders that severely affect the life quality of many people worldwide. Excitatory-inhibitory mechanisms, oxidative stress, and also inflammation systems have been implicated in the pathogenesis of epilepsy. Recent studies have shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its relation with epilepsy is still unclear. This study aimed to investigate the effect of sCT on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole (PTZ)-induced epilepsy model in rats. The study was performed in two steps. In the first step, the effect of sCT on epileptic seizures was evaluated by using electroencephalography (EEG) in fully kindled rats. In the second step, the effect of sCT on epileptogenesis was evaluated by using the kindling process. Glutamate and gamma-aminobutyric acid (GABA), thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1 β), and interleukin 6 (IL-6) were measured in the second group in the brain and serum. Hippocampal regions were stained with hematoxylin-eosin and toluidine blue to evaluate hippocampal neuronal damage histopathologically. Salmon calcitonin showed an antiepileptic effect in fully kindled rats and also prevented the development of epileptogenesis in the kindling process. Besides, sCT decreased glutamate and increased GABA levels. Furthermore, it reduced TBARS levels and increased SOD and CAT levels. On the other hand, it decreased TNF-α levels, IL-1 β levels, and IL-6 levels. Histopathologically, sCT decreased neuronal damage in all hippocampal regions. Our findings are the first preclinical report to show the positive effect of sCT on epileptic seizures and epileptogenesis. Further investigation is required to answer the questions raised about the probable mechanisms involved., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A series of novel indole hydrazide derivatives was synthesized and evaluated for their anticancer activities. Compound 12 exhibited the highest antiproliferative activity against the MCF-7 cell line, with an IC 50 value of 3.01 µM. Treatment of MCF-7 cells with compound 12 led to cell cycle arrest at the G0/G1 phase and also displayed a significant annexin V binding pattern, indicating that compound 12 is effective in apoptotic cell death. The Western blot analysis showed that compound 12 increased the expression of proapoptotic Bax and decreased the levels of the antiapoptotic Bcl-2 protein. It was also observed that MCF-7 cells treated with compound 12 showed reduced levels of procaspase-3 and -9 proteins. Moreover, compound 12 treatment induced a significant DNA damage in MCF-7 cells by increasing H2AX and ATM phosphorylation., (© 2020 Deutsche Pharmazeutische Gesellschaft.)

Background: Heat shock protein 70 (HSP70) is constitutively expressed in normal cells but aberrantly expressed in several types of tumor cells, helping their survival in extreme conditions. Thus, specific inhibition of HSP70 in tumor cells is a promising strategy in the treatment of cancer. HSP70 has a variety of isoforms in the cellular organelles and form different functions by coordinating and cooperating with cochaperones. Cancer cells overexpress HSPs during cell growth and proliferation and HSP network provides resistance against apoptosis. The present study aimed to evaluate quantitative changes in HSPs- and cancerassociated gene expressions and their interactions in the presence of 2-phenylethyenesulfonamide (PES) in MCF-7 cells., Methods: Antiproliferative activity of PES was evaluated using the XTT assay. Inducible HSP70 (HSP70i) levels in the PES-treated cells were determined using the ELISA kit. PCR Array was performed to assess the HSPs- and cancer-pathway focused gene expression profiling. Gene network analysis was performed using the X2K, yEd (V.3.18.1) programs, and web-based gene list enrichment analysis tool Enrichr., Results: The results demonstrated that PES exposure increased the amount of both HSP70i gene and protein expression surprisingly. However, the expression of HSP70 isoforms as well as other co-chaperones, and 17 cancer-associated genes decreased remarkably as expected. Additionally, interaction network analysis revealed a different mechanism; PES induction of HSP70i employs a cell cycle negative regulator, RB1, which is a tumor suppressor gene., Conclusion: PES treatment inhibited MCF-7 cell proliferation and changed several HSPs- and cancer-related gene expressions along with their interactions through a unique mechanism although it causes an interesting increase at HSP70i gene and protein expressions. RB1 gene expression may play an important role in this effect as revealed by the interaction network analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: This study aimed to explore the role of peritoneal ultrafiltration (UF) in cardiorenal syndrome (CRS) patients for fluid and metabolic control., Background: Peritoneal UF is safely and efficiently used for the management of CRS. It has been shown to provide efficient UF in hypervolemic patients., Methods: Thirty (20 males and 10 females) CRS patients were treated by peritoneal dialysis (PD) and UF. The baseline data of the patients (demographics, causes of heart failure, the presence of pacemaker or implantable cardioverter-defibrillator, the need for extracorporeal UF or paracentesis or thoracentesis, comorbidity, drugs, left ventricular ejection fraction [LVEF] and pulmonary artery systolic pressure [PAPs], pericardial effusion, physical examination, body weight, NYHA class, dialysis regime, urine output, N-terminal pro-B-type natriuretic peptide [NT-proBNP] level, hemoglobin, estimated glomerular filtration rate [eGFR], and other routine biochemical determinations) were recorded at the onset, every 6 months, and then annually. Echocardiograms were performed at baseline and after 6 and 12 months. The time points of complications associated with PD, the need for hemodialysis, the day of death, and causes of death were documented., Results: Mean age was 69 ± 8 years (range 49-84 years). The average PD duration was 18.25 ± 14.87 months. According to the CKD-EPI, initial mean GFR was 34.34 ± 11.9 mL/min/1.73 m2 (range 16.57-59.0), and this increased to 45.48 ± 26.04, 45.10 ± 28.58, and 41.10 ± 25.68 mL/min/1.73 m2 in the third, sixth, and twelfth months, respectively. There was a significant increase in the first 3 months and a significant decrease between the third and twelfth months (respectively, p = 0.018 and p = 0.043). There was no difference in eGFR levels between baseline and the end of the first year (p = 0.217). In the first 3 months, there was a significant decline in urea levels to 79.38 ± 36.65 from 109.92 ± 42.44 mg/dL and this was maintained until the end of the first year of PD therapy (after 3 months, p = 0.002; after 1 year, p = 0.024). However, there was no significant change in creatinine levels within the first year (p = 0.312). There was a significant increase in hemoglobin level up to the end of the first year of PD (after 3 months, p = 0.000; after 12 months, p = 0.013). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). Functional capacity (according to NYHA classification) improved in all patients by the third month of PD treatment (p < 0.001). This early improvement was maintained in many patients during the following 12 months (p < 0.001). There was a marked decrease in NT-proBNP levels in the first 6 months (p = 0.011). At the end of the first year, there was an approximate 15% reduction in NT-proBNP levels (p = 0.647). Hospitalizations decreased to 6 ± 15 days/patient-year (range 18-122 days) from 62 ± 24 days/patient-year (p = 0.000)., Conclusion: Peritoneal UF is a treatment method that maintains renal function and electrolyte balance, improves cardiac function, and reduces hospitalizations in CRS patients. We observed that this treatment significantly increased functional capacity and quality of life and significantly reduced hospital admissions., (© 2020 S. Karger AG, Basel.)

Objective: This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey., Methods: Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined., Results: GC-MS analysis revealed the presence of 31 compounds in P. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher α-glucosidase inhibitory activity, and both extract showed strong α-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039-2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC 50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively., Conclusion: Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 Published by Elsevier B.V.)

Background: As a member of serine/threonine-protein kinase, Polo.like kinase 1 (PLK1) plays crucial roles during mitosis and also contributes to DNA damage response and repair. PLK1 is aberrantly expressed in many types of tumor cells and increased levels of PLK1 are closely related to tumorigenesis and poor clinical outcomes. Therefore, PLK1 is accepted as one of the potential targets for the discovery of novel anticancer agents. The objective of this study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280, against MCF-7, human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human prostate cancer cells, as well as non-cancerous L929 fibroblast cells., Methods: Antiproliferative activity of RO3280 was examined using the XTT assay. Flow cytometry assay was performed to evaluate cell cycle distribution, apoptosis, multicaspase activity, mitochondrial membrane potential, and DNA damage response. Apoptosis with fluorescence imaging studies was also examined., Results: According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells., Conclusion: Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest, and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with specific cancer types., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Plane tree (Platanus orientalis L.) leaves have been employed for centuries in various countries due to their pharmacological value. Therefore, determination of the biological activity of the leaves is of interest. The aim of the study was to evaluate the inhibitory effects against Alzheimer's disease-related enzymes Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE), diabetes mellitus related enzymes α-glucosidase and α-amylase. The antioxidant, anticancer, and antimicrobial activities of the leaves were also studied. According to the results, both water and methanol extracts of P. orientalis demonstrated more α-glucosidase and α-amylase inhibition activity than the antidiabetic drug-acarbose at the same concentration level. In addition, extracts showed good inhibition activity against AChE and BuChE. Significant results were obtained regarding antioxidant, anticancer, and antimicrobial activities. These results are very promising especially for the improvement of pharmaceutical formulations to treat various diseases such as age-related diseases, cancer, diabetes etc. and it is necessary to conduct further experiments.

Objectives: Rho-kinases (ROCKs), are one of the dynamic structures of the actin cytoskeleton and they mediate different biological processes, including regulation of calcium sensitivity of smooth muscle contraction. The activation of Rho A/ROCK system is thought to be effective on the termination time of the pregnancy process. The aim of this study, was to investigate in vitro effects of the ROCK enzyme inhibitors, clinically available fasudil hydrochloride, and a new promising inhibitor AS1892802, on the contractions of isolated pregnant rat myometrium., Study Design: Term pregnant Wistar albino rats (n=12), weighing 200-220g, were used in this study. Myometrial tissues obtained from rats were dissected into four full-thickness longitudinal muscle strips and then myometrial tension was recorded isometrically. The inhibitory effects of cumulative concentrations of AS1892802 and of fasudil hydrochloride in the presence and absence of ODQ (guanylate cyclase inhibitor), l-NAME (nitric oxide synthase inhibitor) and l-NNA (endothelial nitric oxide synthase inhibitor) on oxytocin-induced myometrial contractions were measured, and values for -log10EC50 (pD2) and mean maximal inhibition (Emax) were compared., Results: Both ROCK inhibitors, AS1892802 and fasudil hydrochloride starting from the concentrations of 10(-6)M reached statistical significance on contraction amplitude and frequency of myometrial strips (p<0.05). The inhibition of the amplitude and frequency of myometrial contractions was antagonized with ODQ (10(-5)M; only amplitude), l-NAME (3×10(-5)M) and l-NNA (10(-5)M) (p<0.05)., Conclusion: These results suggest that fasudil hydrochloride and AS1892802 may contribute to the development of new tocolytic drugs. We conclude that AS1892802 and fasudil hydrochloride perform this inhibitory effect partially through ROCK inhibition and the NO/cGMP pathway., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)