Endometrial cancer (EC) is a gynecological malignancy classified into two biologically distinct subtypes, Type I and Type II EC. The more aggressive Type II EC exhibits a poor response to conventional platinum-based chemotherapy. Propofol, an anesthetic agent in gynecologic surgery, has been reported to exert antitumor effects beyond anesthesia; however, its role as a chemoadjuvant in EC remains insufficiently explored. In this study, we investigated the effects of propofol combined with carboplatin on drug resistance- and metastasis-associated microRNAs and genes using in vitro and in vivo Type II EC model. Propofol treatment significantly reduced cancer cell viability and migratory capacity, while the combination treatment showed greater antimetastatic effects compared with carboplatin alone. In xenograft models, combination therapy resulted in a significant reduction in tumor volume and suggested reduced metastatic involvement in lung and liver tissues. Molecular analyses revealed downregulation of oncogenic microRNAs (miR-21, miR-135a) and upregulation of tumor-suppressive microRNAs (miR-34b, miR-98), accompanied by reduced mTOR, c-Myc, MRP7, and N-cadherin expression and increased PTEN and HMGB1 levels. Collectively, these findings indicate that propofol is associated with greater antitumor effects when combined with carboplatin, accompanied by changes in miRNA-gene expression patterns.

Endometrial cancer (EC) is a gynecological malignancy classified into two biologically distinct subtypes, Type I and Type II EC. The more aggressive Type II EC exhibits a poor response to conventional platinum-based chemotherapy. Propofol, an anesthetic agent in gynecologic surgery, has been reported to exert antitumor effects beyond anesthesia; however, its role as a chemoadjuvant in EC remains insufficiently explored. In this study, we investigated the effects of propofol combined with carboplatin on drug resistance– and metastasis-associated microRNAs and genes using in vitro and in vivo Type II EC model. Propofol treatment significantly reduced cancer cell viability by 28% and migratory capacity by 34% (p < 0.01), while combination treatment enhanced antimetastatic effects compared with carboplatin alone. In xenograft models, combination therapy resulted in a 42% reduction in tumor volume (p < 0.001) and markedly decreased lung and liver metastasis. Molecular analyses revealed downregulation of oncogenic microRNAs (miR-21, miR-135a, miR-449) and upregulation of tumor-suppressive microRNAs (miR-34b, miR-98), accompanied by reduced mTOR, c-Myc, MRP7, and N-cadherin expression and increased PTEN and HMGB1 levels. Collectively, these findings indicate that propofol enhances carboplatin antitumor efficacy through epigenetic modulation of microRNA–gene networks and may represent an adjuvant strategy in Type II EC.

BACKGROUND:Spinal cord injury is a devastating trauma that leaves survivors at risk for several medical complications throughout their lives. Lercanidipine, a third-generation calcium channel blocker, possesses anti-apoptotic, anti-inflammatory, and antioxidative properties. This study aimed to evaluate the neuroprotective effects of lercanidipine in an experimental spinal cord trauma model.METHODS:Twenty-one Wistar rats were randomly assigned to three groups. Group 1 (G1) underwent laminectomy. Group 2 (G2) were subjected to trauma following laminectomy. Group 3 (G3) were exposed to trauma following laminectomy and treated with lercanidipine. Lercanidipine was administered intraperitoneally for seven days. Histopathological and immunohistochemical evaluations were conducted.RESULTS:Regarding Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, there was no significant difference among the groups. However, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) levels were significantly different across the groups. G2 had significantly higher NF-κB levels compared to G1 and G3.CONCLUSION:Lercanidipine, a third-generation calcium channel blocker, is effective against inflammatory responses induced in spinal cord injury. Further studies are required to determine its capability in preventing apoptosis or improving functional recovery. To the best of our knowledge, this study is the first in the literature to examine the neuroprotective effects of lercanidipine on spinal cord injury.

Objective:The implantation period of gestation is a complex process in which numerous molecular pathways play a role.The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of the evolutionarily conserved cascades used to transduce a multitude signals for several biological events such as implantation and uterine receptivity.Previous studies have indicated that the implantation process is disrupted by the lack of proteins involved in this pathway.However, our literature knowledge showed that there is no study evaluated the expression of JAK/STAT signaling pathwayassociated proteins during the implantation period.This study investigated the expression patterns of JAK/STAT signaling pathway-associated proteins in rats by immunohistochemical (IHC) staining according to gestational days. Methods:In this study, thirty Wistar Albino rats weighing 250-300 g, without any problems in their menstrual cycles, were used.The pregnant animals were sacrificed on the 4 th , 5 th , and 6 th days and histochemical and IHC analysis were performed on the uterine tissues taken from these animals.Results: In this study, protein expression of JAK1, JAK2, JAK3, STAT2, STAT3, STAT4, STAT5, and STAT6 belonging to the JAK/STAT pathway was evaluated in the uterine surface epithelium, gland structures, antimesometrial region, cells of the immune system, myometrium, mesometrial region and decidual cells, which are associated with the implantation process.The result of this evaluation reveals that the expression levels of these proteins in the JAK/STAT pathway vary in different days of the implantation period in implantation-related structures. Conclusion:This study indicates that JAK/STAT signaling pathway-associated proteins can function actively in the regulation of the immunological response of the uterus and embryo-uterus interaction during the implantation period in rats.However, the findings obtained from advanced research on JAK/STAT pathway can be used for treating recurrent pregnancy failures and in enhancing assisted reproductive technology.

Doxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-κB), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.

There is still controversy over whether structural and morphological changes can be observed in tissues depending on the carbon dioxide (CO2) nature or the applied intra-abdominal pressures (IAP). This study aimed to investigate the effects of different pressure or CO2 nature used for pneumoperitoneum in gynecological laparoscopic surgery on inflammation, DNA damage, oxidative stress, and histopathological changes in ovarian and peritoneal tissue. For this purpose, forty female rats were randomly divided into 6 groups and different pneumoperitoneum models were created in these groups. Rats in group other than control and sham groups received standard (CD) or heated-humidified CO2 (HH) insufflations at low (4 mmHg) or high pressure (8 mmHg). The ovary and peritoneum sections were evaluated microscopically for apoptotic index (API) and API scoring was calculated. Tissue and plasma interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-α), anti-Mullerian hormone (AMH) and 8-hydroxydeoxyguanosine (8-OHdG) levels were analyzed with enzyme-linked immunosorbent assay (ELISA). The most severe changes occurred in the 8CD group microscopically, while the least severe changes occurred in the 4HH group. All histopathological parameters except for ovarian apoptotic index and peritoneal PCNA at low pressure were higher in the CD group. TNF-α and 8-OHdG levels were higher in the CD group at both low and high pressures. Standard CO2 caused more prominent histopathological changes at high pressures and systemic inflammation in both pressure groups. The least change between the experimental study groups in terms of histopathological and biochemical was observed in the low-pressure heated-humidified group.

Diabetes mellitus (DM) is common metabolic disease that poses a major risk to public health and fertility. Previous studies indicate that DM may cause male infertility by triggering oxidative stress and germ cell apoptosis in the testis. Due to the undesirable effects of known antidiabetic drugs, scientists have begun to investigate the use of alternative drugs to control infertility complications observed in men. In this context, present study aimed to investigate the possible antiapoptotic effect of losartan against DM-induced testicular germ cell apoptosis. Expreimental DM model was induced by intraperitoneal injection of streptozocin (STZ, 55 mg/kg) to 28 rats, which were then randomly assigned to 4 groups; 1 mL saline solution was given to DM + saline group by oral gavage, 5 mg/kg/day oral losartan was given to DM + low-dose losartan, 20 mg/kg/day oral losartan was given to DM + mid-dose losartan and, 80 mg/kg/day oral losartan was given to DM + high-dose losartan group for 4 weeks. Bax, Bcl-2 and cleaved-Caspase 3 immunoexpression, terminal-deoxynucleotidyl transferase dutp nick end labeling (TUNEL), Annexin-V and Real Time PCR analyses performed to evaluate antiapoptotic effects of losartan on diabetic rats’ testis. In addition, biochemical analyzes carried out to evaluate change in oxidative stress. The results showed that losartan may have dose-related antiapoptotic effects on rats’ testis via decreasing oxidative stress.

BACKGROUND:Central nervous system infection after neurosurgical procedures is a severe complication with high morbidity rates and sometimes mortality. Our experimental study aimed to investigate the biochemical and histopathologic effects of vancomycin on neural tissues when applied to the cisterna magna.METHODS:Wistar albino rats were randomly divided into 4 groups: Control (Group 1) and different vancomycin dose groups (Groups 2, 3, and 4). In Group 1, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mL 0.9% NaCI (normal saline) was administered into the subarachnoid space. In the study groups, 0.1 mL cerebrospinal fluid was drained from the cisterna magna and 0.1 mg/200g rat per day (Group 2), 0.2 mg/200g rat per day (Group 3), and 0.4 mg/200g rat per day (Group 4) vancomycin were administered into the subarachnoid space for 7 days. All rats were sacrificed on the eighth day. Serum superoxide dismutase and catalase levels were measured. Histopathologic and immunohistochemical analyses were conducted.RESULTS:The findings showed that the administration of 0.2 and 0.4 mg/kg doses had significant differences in superoxide dismutase and catalase activity compared with the controls (P < 0.05). These vancomycin doses also induced the apoptotic process, and the enzyme activity results correlated with immunohistochemical results.CONCLUSIONS:Dose-related neurotoxicity of intrathecal vancomycin was shown at the cellular level. The importance of dose regulation of intrathecal vancomycin has come into view. To our knowledge, this is the first study in the literature that has investigated the neurotoxic effects of vancomycin.

Diabetic neuropathy (DN) is the most common degenerative complication associated with Diabetes Mellitus. Despite widespread awareness about DN, the only effective treatments are blood glucose control and pain management. The aim of the current study was to determine the effect of intramuscular adipose-derived mesenchymal stem cell (AMSC) transplantation on sciatic nerves in DN using EMG and histological analyses. A total of 27 mice were randomly divided into three groups: control group, DN group and AMSC group. In EMG, CMAP amplitude in the sciatic nerves was lower, but distal latency was higher in the DN group compared with the control group. CMAP amplitude in the sciatic nerves was higher in the AMSC group compared with the DN group. Distal latency in the sciatic nerve was lower in the AMSC group compared with the DN group. Histologic examination of the tissues in the animals treated with AMSC showed a remarkable improvement in microscopic morphology. Fluorescence microscopy analyses demonstrated that intramuscularly transplanted AMSC was selectively localized in the sciatic nerves. Transplantation of AMSC increased protein expression of S100, cdk2, NGF and DHH, all of which, interfered with DN onset in sciatic nerves. The findings of the present study suggest that AMSC transplantation improved DN through a signal-regulatory effect on Schwann cells, neurotrophic actions and restoration of myelination.

Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric diseases that are characterized by abnormalities of thought, behaviour, cognition and mood. The genetic findings obtained from past molecular genetics research failed to elucidate the molecular pathogenesis of SZ and BD and this situation showed that the risk factors for these diseases were not solely due to the DNA sequence. On the other hand, evidence from cell, animal and postmortem brain studies suggest that abnormal epigenetic mechanisms are important actors in the etiology of complex diseases such as SZ and BD. In this review, epigenetic evidences that obtained from DNA methylation, post-translational histone modifications and non-coding RNA studies in SZ and BD were summarized and the importance of this evidences for advances in the diagnosis and treatment of SZ and BD were discussed briefly.

Cancer, which causes the deaths of millions of people, is an important public health problem worldwide. Despite significant advances in the diagnosis and treatment of cancer, survival rates are still insufficient in progressive cancers. Today, one of the most important reasons for not being able to reach the desired level in the fight against progressive cancer types is cancer stem cells (CSCs). The ineffectiveness of conventional therapies on CSCs has made it necessary to investigate the molecular mechanisms and signaling pathways used in the survival, drug resistance, and metastasis of CSCs. In this context, studies investigating the biology of CSCs suggest that lipid metabolism and extracellular vesicles are critical for understanding the stemness and metastasis of these cells. These studies have demonstrated that a number of molecules play a vital role in resistant to apoptosis in CSCs, including the cellular FLICE-inhibitor protein (c-FLIP), which inhibits TRAIL-induced extrinsic apoptosis. Another important output of these studies is the demonstration of the relationship of the cancer microenvironment in terms of epithelial-mesenchymal transition, which CSCs frequently use in the metastasis process. In addition, studies investigating the differences in glycosylation observed in CSCs and investigating cancer vaccines are promisng. These findings will strengthen our aresnal in the fight against cancer. In this article, we summarize current molecular studies on CSCs, an important target in novel cancer therapies.

Background/aim: Losartan, an antihypertensive drug, is highly preferred in patients with diabetes mellitus (DM) and hypertension because of its retarding effect on diabetic nephropathy. In this study, we investigated the potential therapeutic effect of different doses of losartan on hepatic damage in a streptozotocin (STZ, 50 mg/kg)-induced DM model in rats. Materials and methods: In this study, five different groups were formed: control, DM, low-dose losartan (5 mg/kg), mid-dose losartan (20 mg/kg), and high-dose losartan (80 mg/kg). Liver tissues of experimental groups were evaluated immunohistochemically for TUNEL, iNOS, eNOS, VEGF, and NF-kappa B pathways. In addition to immunohistochemical analysis, analyses of SOD and MDA, which are oxidative stress markers, were also performed and the results were evaluated together. Results: When biochemical and immunohistochemical findings were evaluated together, it was found that the results obtained from the mid-dose losartan group were closer to those of the control than the other groups. Conclusion: This study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating iNOS, eNOS, VEGF, and NF-kappa B protein expressions in DM-induced hepatic damage.

Doxorubicin (DOX) is an anthracycline derivative antibiotic that still frequently used in the treatment of solid tumors and hematological malignancies. The clinical use of DOX is largely restricted due to acute and chronic renal, cardiac, hematological, and testicular toxicities. Previous studies have indicated that oxidative stress, lipid peroxidation, and apoptosis in germ cells are the main factors in DOX-induced testicular toxicity, but the entire molecular mechanisms that responsible for DOX-induced testicular damage are not yet fully understood. Fluvastatin is a cholesterol-lowering agent that acts by inhibiting hydroxylmethyl glutaryl coenzyme A, the key enzyme for cholesterol biosynthesis. In addition to its cholesterol-lowering effect, fluvastatin showed an antioxidant effect by cleaning hydroxyl and superoxide radicals and this drug could have a protective effect by acting on the mammalian target of rapamycin (mTOR) signal pathway in testicular damage caused by obesity. This study aimed to investigate the possible protective and therapeutic effects of fluvastatin on the DOX-induced testicular toxicity model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction analyses. The present study indicates that fluvastatin may have a protective and therapeutic effect by removing reactive oxygen species and by regulating the mTOR, connexin 43, and matrix metalloproteinase 9 protein and messenger ribonucleic acid expressions, which play an important role in regulating the blood–testis barrier. On the other hand, the use of fluvastatin as a protective/prophylactic agent was found to be more effective than the use of this drug for treatment. In light of this information, fluvastatin may be a candidate agent that can be used to prevent testicular toxicity observed in men receiving DOX treatment.

Embryonic developmental stages and regulations have always been one of the most intriguing aspects of science. Since the cancer stem cell discovery, striking for cancer development and recurrence, embryonic stem cells and control mechanisms, as well as cancer cells and cancer stem cell control mechanisms become important research materials. It is necessary to reveal the similarities and differences between somatic and cancer cells which are formed of embryonic stem cells divisions and determinations. For this purpose, mouse embryonic stem cells (mESCs), mouse skin fibroblast cells (MSFs) and mouse lung squamous cancer cells (SqLCCs) were grown in vitro and the differences between these three cell lines signalling regulations of mechanistic target of rapamycin (mTOR) and autophagic pathways were demonstrated by immunofluorescence and real-time polymerase chain reaction. Expressional differences were clearly shown between embryonic, cancer and somatic cells that mESCs displayed higher expressional level of Atg10, Hdac1 and Cln3 which are related with autophagic regulation and Hsp4, Prkca, Rhoa and ribosomal S6 genes related with mTOR activity. LC3 and mTOR protein levels were lower in mESCs than MSFs. Thus, the mechanisms of embryonic stem cell regulation results in the formation of somatic tissues whereas that these cells may be the causative agents of cancer in any deterioration.

Amac: Yasam; baslangic, hayatta kalma ve olumu iceren hucrelerin devamli olan dongusunden olusmaktadir. Hucreler devamli olarak bolunur, farklilasir ve somatik hucreleri olustururlar. Somatik hucreler de belli bir noktada kanser hucrelerini olusturup kok hucreler ile benzer karakteristikleri paylasabilmektedirler. Bu donemlerdeki surecler, somatik hucrelerde anormallige egilimi ve kanser hucrelerine donusumu tanimlamak icin onemlidir. Kanserin ortaya cikisini ve ilerleyisini kontrol etmek icin, hayatta kalma mekanizmalari ozellikle de epitelyal-mezenkimal gecis (EMG) ve iltihaplanma onemlidir. EMG, hem embriyonik gelisim asamalarinda, hem de kanser ilerlemesinde ortaya cikar ve bu surec ozellikle molekuler temelli tedavi icin terapotik hedef olabilir. Gerec ve Yontem: EMG, MAP-Kinaz ve inflamasyon yolaklarinin gen ekspresyon seviyesinde karsilastirilmasinda kanser hucreleri temsili icin fare skuamoz akciger kanseri hucreleri (SqLCCs), somatik kokenli hucre ornegi olarak fare derisi fibroblastlari (MSF'ler) ve embriyonik kok hucre olarak da fare embriyonik kok hucreleri (mEKH'ler) kullanilmistir. ERK 1/2, Vimentin ve Twist'in immunofloresan boyama protein duzeyleri ayni hucrelerde karsilastirilarak incelenmistir. Bulgular: MSF'lerde ve SqLCC'lerde ERK1/2 protein ekspresyonu benzer iken mEKH’lerde ekspresyonu en dusuk bulunmustur. Ayrica, Twist ve Vimentin ifadesi istatistiksel olarak uc hucre hattinda farkli cikmistir. EMG'nin gen ekspresyon profiline ve MAPK sinyal yolaginin destekledigi inflamasyona gore, ozellikle Sparc, Vimentin, Mapksp1 ve Il24 gibi belirgin genlerde ekspresyon profilleri birbirinden cok farkli bulunmustur. Sonuc: Uc farkli hucre hatti hem gen hem de protein ekspresyonunda farkli ozellikler gostermistir. Bu nedenle, bu molekuller terapotik hedef belirlenmesinde potansiyel itici guc olabilir.

Hücre davranışı ve farklılaşmasının yanı sıra hücre bölünme modeli de canlılar için hayati önem taşımaktadır. Hücresel farklılaşma ve hücre çeşitliliği, doğrudan ve dolaylı olarak erken embriyonik aşamada hücre iskeleti, hücre polaritesi, hücre içi ve hücre dışı sinyaller gibi biyolojik süreçlerin yanı sıra, hücre şekli ve hareketinden de etkilenir. Atipik hücre davranışı, embriyogenezde ve bazen onkogenezde gözlenmektedir. Hücre içi trafik, hücrenin dışarıdan gelen sinyallere verdiği cevaplar ve hücre davranışı yönünden daha kapsamlı değerlendirilmelidir. Bu derlemenin amacı: hücre davranışının anlaşılmasında önemli yer tutan; hücre bölünme mekanizmaları açısından hücre şekli, hücrenin farklılaşma kapasitesi, hücre iskeleti, hücre motilitesi ve hücre polaritesi kavramlarını birbirleri ile ilişkilendirerek açıklamaktır.

BACKGROUND:Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the spine and sacroiliac joints. Macrophage migration inhibitory (MIF) factor is a regulatory cytokine that inhibits random immune cell migration. MIF gene promoter polymorphisms play a role in the progression of several inflammatory disorders.AIMS:To investigate the relationship between the MIF gene -173 G/C single-nucleotide polymorphism (SNP) and AS.STUDY DESIGN:Cross-sectional study.METHODS:In this study, a total of 161 AS and 194 normal controls were recruited. The MIF gene -173 G/C SNP was analyzed by polymerase chain reaction using the restriction fragment length polymorphism method.RESULTS:There was no significant difference between groups in terms of genotype distribution (p>0.05). When wild-type G/G and G/C+C/C genotypes are compared in terms of clinical characteristics, there is a significant difference between the average age and the duration of disease in AS patients (p<0.05).CONCLUSION:No significant relationship between AS disease and MIF -173 G/C polymorphism was found. MIF -173 G/C polymorphism (C allele) may affect the time of onset and the duration of disease in AS patients.