The hepatoprotective potential of tannic acid against doxorubicin-induced hepatotoxicity: Insights into its antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Doxorubicin (DOX), which is frequently used in cancer treatment, has limited clinical use due to adverse effects on healthy tissues, especially the liver. Therefore, it is necessary to research the molecular basis of DOX-induced organ and tissue damage and protective agents. In this study, we aimed to examine the protective effects of tannic acid (TA) against DOX-induced hepatoxicity in experimental rat models. Rats were randomly divided into four experimental groups: the untreated control, DOX, TA, and cotreatment (DOX + TA) groups. We investigated the antioxidant system's main components and oxidative stress indicators. Moreover, we examined alterations in the mRNA expression of critical regulators that modulate apoptosis, inflammation, and cell metabolism to better understand the underlying factors of DOX-induced liver toxicity. The results showed that DOX exposure caused an increase in MDA levels and a significant depletion of GSH content in rat liver tissues. Consistent with oxidative stress-related metabolites, DOX was found to significantly suppress both mRNA expression and enzyme activities of antioxidant system components. Moreover, DOX exposure had significant adverse effects on regulating the other regulatory genes studied. However, it was determined that TA could alleviate many of the negative changes caused by DOX. The results of the present study indicated that TA might be considered a versatile candidate that could prevent DOX-induced hepatotoxicity, possibly by preserving cell physiology, viability, and especially redox balance.

The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways.

Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX-induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity.

The interplay between doxorubicin chemotherapy, antioxidant system, and cardiotoxicity: Unrevealing of the protective potential of tannic acid.

Cardiotoxicity is the leading side effect of anthracycline-based chemotherapy. Therefore, it has gained importance to reveal chemotherapy-supporting strategies and reliable agents with their mechanisms of action. Tannic acid (TA), a naturally occurring plant polyphenol, has diverse physiological effects, including anti-inflammatory, anticarcinogenic, antioxidant, and radical scavenging properties. Therefore, this study was designed to investigate whether TA exerts a protective effect on mechanisms contributing to anthracycline-induced cardiotoxicity in rat heart tissues exposed to doxorubicin (DOX). Rats were randomly divided into control and experimental groups and treated with (18 mg/kg) DOX, TA (50 mg/kg), and DOX + TA during the 2 weeks. Cardiac gene markers and mitochondrial DNA (mtDNA) content were evaluated in the heart tissues of all animals. In addition to major metabolites, mRNA expression changes and biological activity responses of components of antioxidant metabolism were examined in the heart tissues of all animals. The expression of cardiac gene markers increased by DOX exposure was significantly reduced by TA treatment, whereas mtDNA content, which was decreased by DOX exposure, was significantly increased. TA also improved antioxidant metabolism members' gene expression and enzymatic activity, including glutathione peroxidase, glutathione s-transferase, superoxide dismutase, catalase, and thioredoxin reductase. This study provides a detailed overview of the current understanding of DOX-induced cardiotoxicity and preventive or curative measures involving TA.

Comparison of two different suction curettage methods in cesarean scar pregnancy treatment.

BACKGROUND: Cesarean scar pregnancy (CSP), the incidence of which is increasing, can lead to life-threatening consequences. In this study, it was aimed to compare the results of two different ultrasound-assisted suction curettage (SC) approaches that we applied to endogenous type CSPs in different time periods. METHODS: Patients who were diagnosed with CSP and treated with SC in the early pregnancy service between January 2012 and March 2019 were included in the study. While classical SC was applied until December 2016, patients were treated with SC modified by us after this date. Demographic characteristics, preoperative clinical findings, intraoperative characteristics and postoperative short-term follow-up of these two groups of patients belonging to different time periods were compared. RESULTS: 34 patients were treated with classic SC (Group 1) and 32 patients with modified SC (Group 2). The amount of decrease in Hemoglobin values measured at the sixth hour postoperatively compared to the preoperative period was found to be less in group 2 (1.01 ± 0.67 g/dl) than in group 1 (1.39 ± 0.85 g/dl) (p = 0.042). The treatment failure rate was found to be lower in group 2 (p = 0.028). According to the results of multiple logistic regression analysis of significant factors associated with treatment outcome, myometrial thickness measurement and the largest gestational diameter measurement were found to be significant independent factors. CONCLUSION: In CSP cases, SC procedure with abdominal ultrasonography is an effective and reliable approach. At the beginning of this surgical procedure, if the gestational sac is removed from the uterine wall with the curettage cannula before suction, the success of the procedure will increase even more.

Impact of molecular and histopathological findings on FIGO 2009 stage I endometrial cancer: Transition to FIGO 2023 staging system.

AIM: This study aims to investigate the impact of integrating molecular and histopathological findings into the revised International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system on patients initially diagnosed with stage I endometrial cancer (EC) according to the FIGO 2009 criteria. METHODS: A cohort of 197 EC patients, initially classified as stage I under FIGO 2009, underwent restaging based on the updated FIGO 2023 criteria. The patients' molecular and histopathological characteristics were documented, and their impact on upstaging was analyzed. RESULTS: Molecular profiling was conducted for 81.2% (160/197) of the patients, revealing that 55.3% (109/197) were classified as non-specific molecular profile, 14.7% (29/197) as mismatch repair deficiency, 11.2% (22/197) as p53 abnormality (p53abn), and 18.8% (37/197) as unknown. Upstaging was identified in 26.9% (43/160) of the 160 patients with known molecular profiles. Among the upstaged patients, 51.2% experienced upstaging due to p53 abnormality, 20.9% due to substantial lymphovascular space invasion (LVSI), 20.9% due to aggressive histological types, and 6.9% due to high grade. CONCLUSIONS: The introduction of the molecular profile into the revised FIGO 2023 staging system for stage I EC has led to notable changes in the staging of approximately one-fifth of patients. While p53 abnormalities have emerged as the most influential factor contributing to the upstaging, LVSI and aggressive histological types also represent significant contributing factors.

Do First-Trimester Subchorionic Hematomas Affect Pregnancy Outcomes?

OBJECTIVE: The aim of this study is to investigate the relationship between first trimester subchorionic hematomas and pregnancy outcomes in women with singleton pregnancies. MATERIAL AND METHODS: Between January 2018 and January 2019, patients who had a single pregnancy between the 6th and 14th weeks of their pregnancy and were hospitalized with the diagnosis of abortus imminens in the early pregnancy service were included in the study. According to the ultrasonographic examination, those with subchorionic hematoma and those with no hematoma were compared in terms of demographic data, pregnancy outcomes and pregnancy complications. RESULTS: 400 abortus immines cases with subchorionic hematoma and 400 abortus imminens cases without subchorionic hematoma were compared. Preterm delivery percentages were similar in both groups, however abortus percentage was significantly higher in the hematoma group (34.2 vs. 24.7%; p=0.007). In addition, it was revealed that the presence of subchorionic hematoma before the 20th gestational week increased the risk of miscarriage 1.58 times. However, no data could be found in the study that could correlate the size of the hematoma with pregnancy loss. CONCLUSION: The presence of subchorionic hematoma increases abortion rates in abortus imminens cases. And the presence of subchorionic hematoma in cases with ongoing pregnancy does not increase the complications of delivery.

The effect of medical and social conditions on the mode of delivery: a prospective questionnaire-based study applied to 404 Turkish obstetricians.

PURPOSE: To identify the factors that influence provider's decisions on method of delivery in a country where national cesarean delivery rate (CDR) among all births increased steadily from 21 to 56% in a 16-year period. METHODS: We planned nine birth scenarios, in which both delivery modes were plausible, and we used self-administered questionnaire to ask obstetricians for their preferred mode of delivery in these scenarios. If the choice was cesarean delivery (CD), the provider was asked to state the reason for choosing this method. We grouped respondents according to number of years in their occupation, working sector (state, university or private hospital) and academic degree. RESULTS: Four hundred and four obstetricians completed the questionnaire. Preference for CD in all scenarios was comparable between male and female obstetricians (p = 0.334) and between specialists, associate professors and professors (p = 0.812). The most frequent reason for choice of CD in all nine scenarios was fear of fetal risk and/or fear of litigation. CONCLUSION: Fear of litigation was found to be the major factor influencing CD choice. This fear not only increases the CDR but also results in loss of training in breech delivery and operative vaginal delivery, forming a vicious cycle.

Tonic-Clonic Seizure in Patient With SLE: Posterior Reversible Encephalopathy Syndrome, or a Neuropsychiatric Manifestation of SLE?

Posterior reversible encephalopathy syndrome (PRES) is a clinically and radiologically diagnosed reversible sudden onset disease with many neurological symptoms. SLE is the most common cause of PRES among autoimmune diseases. Many factors, such as SLE activity, hypertension, hematological and renal diseases, lymphopenia dyslipidemia, and immunosuppressive treatments, can trigger PRES in SLE. We wanted to draw attention to the difference between neuropsychiatric systemic lupus erythematosus (SLE) and PRES in a patient with SLE and the triggers for developing PRES in SLE by presenting a hypertensive patient on immunosuppressive therapy who had just started haemodialysis treatment and had generalised tonic-clonic seizures.

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol.

OBJECTIVE: The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. MATERIALS AND METHODS: A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (ß-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. RESULTS: The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). CONCLUSION: Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

OBJETIVO: A disponibilidade de marcadores confiáveis e baratos que podem ser usados para determinar o risco de ruptura durante o tratamento com metotrexato (MTX) em gestações ectópicas (GEs) é considerável. O objetivo do presente estudo é investigar o papel de marcadores inflamatórios sistêmicos, como leucócitos (ou glóbulos brancos, glóbulos brancos), a relação neutrófilo-linfócito (NLR) e largura de distribuição de plaquetas (PDW), que estão entre os parâmetros do hemograma completo (hemograma), na predição de ruptura de PEs sob tratamento com MTX. MATERIAIS E MéTODOS: Foram analisados retrospectivamente 161 pacientes com EP tubária submetidas a protocolo de dose única de metotrexato (MTX), sendo que o grupo controle (n = 83) incluiu pacientes curadas com MTX, enquanto o grupo roto (n = 78) incluíram pacientes operadas por ruptura tubária durante o tratamento com MTX. As características de EP, beta-gonadotrofina coriônica humana (ß-hCG), achados ultrassonográficos e marcadores derivados de CBC, como WBC, NLR e PDW, foram investigados comparando os dois grupos. RESULTADOS: A RNL foi maior no grupo roto, de 2,92 ± 0,86%, e significativamente menor no grupo controle, de 2,09 ± 0,6%. Da mesma forma, o PDW foi maior (51 ± 9%) no grupo roto, e foi significativamente menor a (47 ± 13%) no grupo controle (p < 0,05). Outros parâmetros do hemograma foram semelhantes em ambos os grupos (p > 0,05). CONCLUSãO: Marcadores inflamatórios sistêmicos derivados do hemograma podem ser facilmente aplicados para predizer o risco de ruptura tubária na Eps, uma vez que o hemograma é um exame de baixo custo e fácil aplicação, solicitado primeiramente a cada paciente durante a internação.

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol / Predição de ruptura por hemograma completo em gestações ectópicas tubárias tratadas com protocolo de dose única de metotrexato

Abstract Objective The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. Materials and Methods A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (β-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. Results The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). Conclusion Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

Resumo Objetivo A disponibilidade de marcadores confiáveis e baratos que podem ser usados para determinar o risco de ruptura durante o tratamento com metotrexato (MTX) em gestações ectópicas (GEs) é considerável. O objetivo do presente estudo é investigar o papel de marcadores inflamatórios sistêmicos, como leucócitos (ou glóbulos brancos, glóbulos brancos), a relação neutrófilo-linfócito (NLR) e largura de distribuição de plaquetas (PDW), que estão entre os parâmetros do hemograma completo (hemograma), na predição de ruptura de PEs sob tratamento com MTX. Materiais e Métodos Foram analisados retrospectivamente 161 pacientes com EP tubária submetidas a protocolo de dose única de metotrexato (MTX), sendo que o grupo controle (n = 83) incluiu pacientes curadas com MTX, enquanto o grupo roto (n = 78) incluíram pacientes operadas por ruptura tubária durante o tratamento com MTX. As características de EP, beta-gonadotrofina coriônica humana (β-hCG), achados ultrassonográficos e marcadores derivados de CBC, como WBC, NLR e PDW, foram investigados comparando os dois grupos. Resultados A RNL foi maior no grupo roto, de 2,92 ± 0,86%, e significativamente menor no grupo controle, de 2,09 ± 0,6%. Da mesma forma, o PDW foi maior (51 ± 9%) no grupo roto, e foi significativamente menor a (47 ± 13%) no grupo controle (p < 0,05). Outros parâmetros do hemograma foram semelhantes em ambos os grupos (p > 0,05). Conclusão Marcadores inflamatórios sistêmicos derivados do hemograma podem ser facilmente aplicados para predizer o risco de ruptura tubária na Eps, uma vez que o hemograma é um exame de baixo custo e fácil aplicação, solicitado primeiramente a cada paciente durante a internação.

From Genetics to Functional Genomics: Improvement in Drought Signaling and Tolerance in Wheat.

Drought being a yield limiting factor has become a major threat to international food security. It is a complex trait and drought tolerance response is carried out by various genes, transcription factors (TFs), microRNAs (miRNAs), hormones, proteins, co-factors, ions, and metabolites. This complexity has limited the development of wheat cultivars for drought tolerance by classical breeding. However, attempts have been made to fill the lost genetic diversity by crossing wheat with wild wheat relatives. In recent years, several molecular markers including single nucleotide polymorphisms (SNPs) and quantitative trait loci (QTLs) associated with genes for drought signaling pathways have been reported. Screening of large wheat collections by marker assisted selection (MAS) and transformation of wheat with different genes/TFs has improved drought signaling pathways and tolerance. Several miRNAs also provide drought tolerance to wheat by regulating various TFs/genes. Emergence of OMICS techniques including transcriptomics, proteomics, metabolomics, and ionomics has helped to identify and characterize the genes, proteins, metabolites, and ions involved in drought signaling pathways. Together, all these efforts helped in understanding the complex drought tolerance mechanism. Here, we have reviewed the advances in wide hybridization, MAS, QTL mapping, miRNAs, transgenic technique, genome editing system, and above mentioned functional genomics tools for identification and utility of signaling molecules for improvement in wheat drought tolerance.

Barley transcript profiles under dehydration shock and drought stress treatments: a comparative analysis.

A microarray including 1654 cDNAs, mainly derived from dehydration-shocked barley leaf tissues, was utilized to monitor expression changes in leaves of barley plants subjected to slow drying conditions (7 d and 11 d: 7d-WS and 11d-WS) in soil and after rehydration. The results were compared with those obtained under shock-like conditions imposed with a 6 h dehydration treatment. A total number of 173 transcripts (approximately 10% of all transcripts profiled) were declared up- or down-regulated in at least one of the conditions tested. The majority of the transcripts were regulated by only one of the drought treatments, with 57% of the differentially expressed transcripts exclusively affected in the dehydration shock treatment, 6% at 7d-WS, 14% at 11d-WS, and 6% after rehydration. Irrespective of the low percentage of transcripts (10%) with similar expression changes between shock and slow stress treatments, a sizeable portion of these transcripts shared a common expression trend under the different drought treatment conditions, as evidenced by low but significant correlations between the fast occurring and the 7d-WS and 11d-WS treatments (r=0.32 and 0.41, P=0.001, respectively). These results are discussed with respect to the merit of different dehydration treatments in the investigation of the changes in transcript profiling.

Identification of drought-inducible genes and differentially expressed sequence tags in barley.

Drought limits cereal yields in several regions of the world and plant water status plays an important role in tolerance to drought. To investigate and understand the genetic and physiological basis of drought tolerance in barley, differentially expressed sequence tags (dESTs) and candidate genes for the drought response were mapped in a population of 167 F8 recombinant inbred lines derived from a cross between "Tadmor" (drought tolerant) and "Er/Apm" (adapted only to specific dry environments). One hundred sequenced probes from two cDNA libraries previously constructed from drought-stressed barley (Hordeum vulgare L., var. Tokak) plants and 12 candidate genes were surveyed for polymorphism, and 33 loci were added to a previously published map. Composite interval mapping was used to identify quantitative trait loci (QTL) associated with drought tolerance including leaf relative water content, leaf osmotic potential, osmotic potential at full turgor, water-soluble carbohydrate concentration, osmotic adjustment, and carbon isotope discrimination. A total of 68 QTLs with a limit of detection score > or =2.5 were detected for the traits evaluated under two water treatments and the two traits calculated from both treatments. The number of QTLs identified for each trait varied from one to 12, indicating that the genome contains multiple genes affecting different traits. Two candidate genes and ten differentially expressed sequences were associated with QTLs for drought tolerance traits.