Corrigendum: Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats.

[This corrects the article DOI: 10.3389/fphar.2023.1305816.].

Evaluation of the expression of LC3-II and BECLIN1 genes of autophagy pathway in patients with hematological malignancies.

Background: Autophagy is a pathway for the degradation of cytoplasmic components, which plays an essential role in various cellular and physiological processes, including cell renewal and survival, and immune responses. While recent studies have shown that they can play a role in cancer treatment, the precise mechanisms of autophagy in leukemogenesis are not fully understood. We have assessed the expression levels of LC3 and BECLIN1 as two crucial autophagy mediators in patients with leukemia. Methods: This cross-sectional study was performed on bone marrow or peripheral blood samples of 61 leukemia patients (24 AML, 20 ALL, and 17 CML) and compared to 18 healthy controls. Real-time PCR was used to quantitate gene expression. SPSS statistics 16.0 and Graph Pad Prism 8.4.2 software were applied for statistical analysis. Results: While BECLIN1 expression was significantly lower in AML, ALL, and CML patients as compared to the control group (p < 0.05), LC3 showed significantly different expression only in the AML patients (P= 0.03). There was no significant correlation between the expression levels of BECLIN1 with LC3 (p> 0.05). Whilst the AML LC3high group had a significantly lower lymphocyte count (P= 0.023), the AML BECLIN1low group had a significantly higher MPV levels (P= 0.044). Furthermore, ALL LC3high group indicated a significantly lower HCT count (P= 0.017). Conclusion: Significant changes in the expression levels of BECLINI and LC3 in hematologic malignancies may indicate a possible role for autophagy in their pathogenesis. However, further studies are warranted to confirm these findings.

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients.

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accompanies a worse survival. In this study, gene expression levels of 5 key players of apoptosis, including DR4, DR5, FAS, caspase 8, and DNA damage-induced apoptosis suppressor (DDIAS), have been evaluated in AML patients compared with controls, aiming to evaluate their possible role and prognostic impact. Methods: This cross-sectional study was performed in the Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. A total of 30 newly diagnosed AML cases as well as 30 healthy controls enrolled in the study. Real-time polymerase chain reaction was used to evaluate the expressions of DR4, DR5, FAS, DDIAS, and caspase 8 genes in cases and controls. Other necessary data, including cytogenetic findings, mutations, French-American-British (FAB) classification, and survival, were retrieved from hospital records and by direct contact with patients. Statistical analysis was done by SPSS software. When appropriate, the Mann-Whitney U, Pearson's correlation, and the t tests were utilized. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The expression of all evaluated genes, including DDIAS (0.89 ± 0.20), DR4 (0.67 ± 0.24), DR5 (0.72 ± 0.24), FAS (0.70 ± 0.25), and Caspase 8 (0.77 ± 0.20) were significantly decreased in AML patients compared with the controls (P < 0.001). Patients with the t (16;16) or inv (16) expressed significantly higher amounts of the FAS gene and those with FLT3 mutation exhibited lower expression of caspase 8. Expression of the evaluated genes showed no significant effect on survival. Conclusion: The expression of DR4, DR5, FAS, and caspase 8 seems to be decreased in AML. Lower expression of these molecules may aid AML cells in avoiding apoptosis because they are involved in the initiation of apoptosis, making them potential targets for treatment.

Molecular biology of microRNA-342 during tumor progression and invasion.

Cancer is considered as one of the main causes of human deaths and health challenges in the world. Various factors are involved in the high death rate of cancer patients, including late diagnosis and drug resistance that result in treatment failure and tumor recurrence. Invasive diagnostic methods are one of the main reasons of late tumor detection in cancer patients. Therefore, it is necessary to investigate the molecular tumor biology to introduce efficient non-invasive markers. MicroRNAs (miRNAs) are involved in regulation of the cellular mechanisms such as cell proliferation, apoptosis, and migration. MiRNAs deregulations have been also frequently shown in different tumor types. Here, we discussed the molecular mechanisms of miR-342 during tumor growth. MiR-342 mainly functions as a tumor suppressor by the regulation of transcription factors and signaling pathways such as WNT, PI3K/AKT, NF-kB, and MAPK. Therefore, miR-342 mimics can be used as a reliable therapeutic strategy to inhibit the tumor cells growth. The present review can also pave the way to introduce the miR-342 as a non-invasive diagnostic/prognostic marker in cancer patients.

Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene.

BACKGROUND: The chimeric enzyme SETMAR (or Metnase) has been associated with several DNA processes, including DNA damage repair through the non-homologous joining pathway and suppression of chromosomal translocation in mouse fibroblasts. SETMAR overexpression has been reported in certain cancers suggesting that it might contribute to the establishment or progression of these cancers. In leukemia, the SETMAR gene transcript variants have not been widely studied. Therefore, this study aimed to quantify 3 predominant SETMAR variants in 2 types of childhood acute leukemia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS: In this study, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the relative expression of 3 SETMAR transcript variants (Var 1, Var 2, and Var A) were evaluated in the bone marrow samples collected from 30 newly diagnosed patients with AML, 65 newly diagnosed patients with ALL, and 15 healthy individuals. RESULTS: The expression of SETMAR variants 1 and A were significantly higher in AML patients compared with controls ( P =0.02, and P =0.009, respectively). Variant A expression was significantly higher in ALL compared with controls ( P =0.003). When comparing the expression in translocation-positive and negative subgroups, the expression of variant 1 was significantly higher in translocation-positive ALL patients ( P =0.03). The variants' distribution patterns differed concerning translocation status ( P =0.041), as variants 1 and A were dominant in the translocation-positive ALL group, and variant 2 was more prevalent in translocation-negative ones. CONCLUSIONS: According to the results, SETMAR showed increased expression in pediatric acute leukemia's bone marrow samples, indicating a role for this molecule in leukemia pathogenesis. As this is the first report of SETMAR expression in pediatric leukemias, further studies are needed to investigate the causality of this association.

Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats.

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor (S. minor) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI. Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted. Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK (p < 0.001) and elevated MDA levels (p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content (p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase (p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers (p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract. Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress.

Deregulation of the Expression of Beclin1 and Light Chain 3(LC3), Autophagy-Related Genes, in COVID-19 Patients.

Background: The autophagy machinery is reported to be employed by Coronaviruses during their replication. Beclin-1 (BECN1) and protein 1 light chain 3 (LC3) are two key elements in the autophagy process, and their inhibition can prevent the replication of some coronaviruses in vitro. Here, we aimed to investigate the expression levels of Beclin-1 and LC3 in COVID-19 patients and healthy controls, hoping to find new therapeutic targets. Methods: This cross-sectional study was conducted in Imam Reza and Ghaem University Hospitals, Mashhad, Iran. Nasopharyngeal samples of 68 consecutive Covid-19 patients and 61 healthy controls, who have been referred to the laboratories for COVID-19 PCR testing between 21 March to 21 September 2021, were used in order to evaluate the expression of BECN1 and LC3 genes using the Real-time quantitative PCR method. Demographic and other laboratory findings of patients were extracted from the hospital electronic system. SPSS Statistics 16.0 and Graph Pad Prism 8.4.2 soft wares were used for statistical analysis. Non-parametric tests were used. Results: BECN1 expression was significantly higher in COVID-19 patients compared to the controls (14.37±18.84 vs. 4.26±7.39, p=0.001). The expression of LC3 gene was significantly lower in patients compared to the controls (1.01±1.06 vs. 1.49±1.12, p=0.007). There was no significant correlation between the expression levels of BECN1 and LC3. Patients with lower BECN1 expression showed significantly higher RBC counts, higher Urea and lower HCO3 levels. The patients in LC3Low group showed significantly lower MCH, MCHC and PH levels compared to the others. Conclusion: Regarding the significant difference in the expression of BECN1 and LC3 in COVID-19 patients compared to the controls, these molecules may have a role in the pathogenesis of this disease. In case of further confirmation of this role, these molecules may be used as possible therapeutic targets.

Cardioprotective Effect of Rheum turkestanicum Against Doxorubicin-Induced Toxicity in Rats.

Background: Doxorubicin as an anti-cancer drug causes cardiotoxicity, limiting its tolerability and use. The mechanism of toxicity is due to free radical production and cardiomyocytes injury. This research evaluated Rheum turkestanicum (R.turkestanicum) extract against doxorubicin cardiotoxicity due to its considerable in vitro antioxidant activity. Methods: Male Wistar rats received 2.5 mg/kg doxorubicin intraperitoneally every other day for 2 weeks to create an accumulative dose. R. turkestanicum was administrated at a dose of 100 and 300 mg/kg intraperitoneally from the second week for 7 days. On the 15th day, the animals were anesthetized and blood was collected from cardiac tissue for evaluation of alanine aminotransferase (ALT), cardiac muscle creatinine kinase (CK-MB), troponin T (cTn-T), lactate dehydrogenase (LDH), and B-type natriuretic peptide brain natriuretic peptide. A cardiac homogenate was also collected to determine superoxide dismutase (SOD), catalase Catalase Activity, malondialdehyde (MDA), and thiols. Histopathology was also performed. Results: Doxorubicin increased all cardiac enzymes and malondialdehyde, correlating with a reduction in SOD, catalase, and thiols. Histopathology revealed extracellular edema, moderate congestion, and hemorrhage of foci. In contrast, administration of R. turkestanicum ameliorated these doxorubicin-induced pathophysiological changes. Conclusion: This study revealed that the extract ameliorated doxorubicin-induced cardiac toxicity via modulation of oxidative stress-related pathways. Liquid chromatography-mass spectrometry analysis of R. turkestanicum indicated several components with potent pharmacological properties.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Retrospective analysis of direct antiglobulin test positivity at tertiary academic hospital over 10 years.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a clinically significant problem that may potentially affect any pregnancy. Direct antiglobulin test (DAT) is considered to be an important test in identifying newborns who are suspected to have HDN. This study aims in reviewing data regarding a positive DAT result concerning etiology and the development of HDN over a period of 10 years. STUDY DESIGN AND METHODS: A retrospective study of all neonates with a positive DAT result between January 2011 and December 2020 was performed. Data were obtained from patients' electronic hospital files, transfusion medicine databases, and medical birth records. Laboratory parameters along with clinical interventions in neonates with a DAT-positive result and a comparison group of DAT-negative neonates were performed. RESULTS: 36,000 deliveries were registered in this period. 176 (2.65 %) neonates had a positive DAT result. ABO-incompatibility was the most common cause with 59.1 %; Rh incompatibility 13.8 %, minor blood group incompatibility, and other RBC-related antibodies 10.1 %, and unspecified etiology in 17 % of cases. Among DAT-positive cases, 32.7 % of neonates were diagnosed with HDN. ABO-incompatibility was the major reason as well. Initial mean total bilirubin levels were higher in the DAT-positive group than the control group (p < 0.001), and these neonates also had a lower initial hemoglobin level (p < 0.001). The need for therapeutic interventions was significantly higher in DAT-positive neonates (p < 0.001) as 86.8 % underwent phototherapy, with 32.7 %, and 17.6 % receiving exchange transfusion (ET) and intravenous immunoglobulin (IVIG), respectively. CONCLUSION: In conclusion, ABO incompatibility was the most common cause for neonatal DAT positivity. Besides the common causes of DAT positivity, there would be rare but important conditions that may lead to a positive result, such as antibodies passively acquired from mothers in the context of alloimmunizations or using drugs. In addition, as a high rate of therapeutic intervention was identified among neonates with a DAT-positive result, there is a crucial need for increasing awareness regarding early diagnosis of the condition, careful monitoring, and the employment of prenatal alloimmunization screening tests.

Standardized extract of Sanguisorba minor attenuates injury in aging rat model via the Nrf2/HO­1 pathway.

Aging promotes damage to vulnerable organs like brain and liver. Sanguisorba minor has been traditionally used to cure various ailments. Few studies have reported pharmacological activities of this medicinal plant. This research aimed to investigate the effects of Sanguisorba minor extract (SME) on brain and liver injury in aging rats and identify the underlying mechanisms. The aging model was developed by subcutaneously injecting D­galactose and simultaneously treating them with SME. After biochemical and pathological assessments, mRNA expression levels of nuclear factor­erythroid factor 2­related factor 2 (Nrf2) and Nrf2­ regulated gene, heme oxygenase­1 (HO­1), in the brain and liver tissues were determined. As a result, malondialdehyde and acetylcholinesterase levels were elevated while total thiol content and superoxide dismutase were reduced in the aging rats. Treatment with the extract remarkably attenuated oxidative injury and pathological changes in liver and brain tissues. Concomitantly, the extract up­regulated Nrf2 and HO­1 genes. Our findings exhibited SME may improve the aging­related brain and liver damage through the Nrf2­HO­1 pathway.

Codelivery of BV6 and anti-IL6 siRNA by hyaluronate-conjugated PEG-chitosan-lactate nanoparticles inhibits tumor progression.

AIMS: Increased expression of inhibitor of apoptosis (IAP) genes has been associated with progressive cancer and chemoresistance. Accordingly, blockade of IAPs by BV6 has resulted in ameliorative outcomes. Interleukin (IL)-6 is another important mediator involved in the growth and survival of tumor cells. Therefore, we hypothesized that simultaneous inhibition of IAPs and IL-6 could be a new promising anti-tumor treatment strategy. MATERIALS AND METHODS: In this study, we generated and characterized hyaluronate-PEG-Chitosan-Lactate (H-PCL) nanoparticles (NPs) to simultaneously deliver IL6-specific siRNA and BV6 to 4T1 (breast cancer) and CT26 (colon cancer) cells, and investigate the anti-tumor properties of this combination therapy both in vitro and in vivo. KEY FINDINGS: H-PCL NPs exhibited good physicochemical properties leading to efficient transfection of cancer cells and suppression of target molecules. Moreover, combination therapy synergistically increased apoptosis, as well as decreased cell migration, proliferation, colony formation, and angiogenesis in both 4T1 and CT26 cell lines and suppressed cancer progression in tumor-bearing mice that was associated with enhanced survival time. SIGNIFICANCE: These findings imply the effectiveness of cancer combination therapy by using H-PCL NPs loaded with anti-IL-6 siRNA and BV6.

Reno-protective effect of Rheum turkestanicum against gentamicin-induced nephrotoxicity.

OBJECTIVES: Gentamicin belongs to the family of aminoglycoside antibiotics and is a preferred drug in developing countries because of its low cost, availability, and potent effects against bacterial. However, gentamicin can induce nephrotoxicity. In this research, hydroalcoholic extract of Rheum turkestanicum was used against gentamicin- induced nephrotoxicity and its effect against gentamicin-induced nephrotoxicity in rats has been investigated. MATERIALS AND METHODS: The rats were placed into one of these groups: saline group, gentamicin group that received gentamicin 80 mg/kg/day for six days, and two treatment groups that received R. turkestanicum intraperitoneally at doses of 100 and 200 mg/kg body weight, respectively, 1 hr before gentamicin injections. Urine samples were collected at 24 hr to measure glucose and protein concentration. Blood samples were collected to determine serum urea and creatinine. One kidney was homogenized to measure malondialdehyde and thiol, and the other kidney was kept for pathological studies. RESULTS: Gentamicin increased the level of urinary glucose and protein, and increased malondialdehyde while it decreased thiol in kidney tissue, and increased the concentration of urea and creatinine in the serum. Histopathological pathology revealed renal damage following gentamicin usage; however, the extract was able to improve gentamicin toxicity. CONCLUSION: R. turkestanicum has positive effects in the attenuation of gentamicin-induced nephrotoxicity.

Correlation between expression of CatSper1,2 and sperm parameters in the gamma irradiated adult mouse testis.

Propose: CatSper protein channels are responsible for the entry of Ca2+ into sperm cells. These proteins play an important role in motility and male fertility. So it is important to find out whether or not environmental factors, such as gamma radiation, have an effect on the expression of Catsper genes. In this study, we investigated the effects of gamma radiation on the expression of CatSper1 and CatSper2 genes. Materials and methods: Twenty-one male NMRI mice were divided into three groups: a control group without gamma radiation, and two experimental groups; Group 1 treated with 1 Gy of gamma radiation, and Group 2 treated with a higher dose of 2 Gy gamma radiation. Testes were removed from all groups of animals 35 days following irradiation and the testicular tissue, processed and embedded in paraffin blocks for sectioning and histological examination. Sperm samples were also taken from the epididymis for microscopic. Sperm parameters such as sperm count, morphology, motility, and viability rates were analyzed. Expression of CatSper genes was evaluated using Real-time PCR. Data were analyzed using the SPSS software and ANOVA test. Results: Our results showed that after treatment with gamma radiation, testes morphology was changed. Epididymal sperm count, motility, and morphology rates were significantly affected in both experimental groups compared to the control group. The relative expressions of CatSper 1 and 2 genes were significantly reduced in the irradiated mice (1 Gy and 2 Gy) than non-irradiated ones. Conclusions: Gamma radiations not only change testes histology and sperm parameters, but also decrease the expression of CatSper 1 and 2 genes in male mice.

Acylated and deacylated quillaja saponin-21 adjuvants have opposite roles when utilized for immunization of C57BL/6 mice model with MOG35-55 peptide.

BACKGROUND: The majority of patients with multiple sclerosis (MS) suffer from central neuropathic pain (CNP). Using experimental autoimmune encephalomyelitis (EAE) model, only a few experiments were performed to assess pain behaviors in MS. To address this issue, complete Freund's adjuvant (CFA) was replaced with an acylated triterpene glycoside saponin adjuvant named quillaja saponin-21 (QS-21) to develop CNP in the EAE mouse model. The deacylated form of QS-21, named QT-0101, has been suggested to have an immunomodulatory effect. Thus, QT-0101 was used as a vaccine adjuvant to modulate the immune system against myelin oligodendrocyte glycoprotein (MOG35-55) antigen. METHODS: In this study, C57BL/6 mice, except for mice in the negative control (PBS) and MOG groups, were divided into three groups and immunized by MOG35-55 emulsified with CFA, QS-21, or QT-0101 adjuvants, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, through the Hot Plate test and the clinical signs, was assessed for 60 days after immunization. On days 21 and 60, mice were sacrificed and the frequency of TCD4+, TCD8+, IL-17+, IL-4+, and CD25+/FoxP3+ cells population in the total splenocytes population was assessed by flow cytometry. Infiltration of Leukocytes into the brain and demyelination of white matter were also evaluated by histopathologic studies. RESULTS: Our results revealed that unlike the MOG+QT-0101 group, the MOG+QS-21 and MOG+CFA groups represented clinical symptoms that mimic the mild relapsing-remitting and monophasic models, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, developed in the bilateral hind paws in the MOG+CFA and MOG+QS-21 mice groups during the onset of neurologic deficits, but it is maintained until completion of the study only in MOG+QS-21 mice group. The frequency of TCD4+, TCD8+ and IL-17+ cells population in the MOG+QS-21 and MOG+CFA mice groups, as well as IL-4+ and CD25+/Foxp3+ cells population in the MOG+QT-0101 mice group, significantly increased in comparison with the PBS mice group. Infiltration of inflammatory cells increased significantly in the MOG+QS-21 and MOG+CFA mice groups compared with the PBS mice group. Demyelination of white matter was identified significantly only in the MOG+CFA mice group compared with the PBS mice group. CONCLUSION: These results showed that QS-21 is a suitable adjuvant for the establishment of a mild relapsing-remitting EAE model for CNP development and open a new avenue to future pre-clinical and clinical research studies related to CNP treatment. Nevertheless, QT-0101 seems to have the potential to act as a vaccine adjuvant with immunomodulatory property against auto-antigens.

Down-regulation of CatSper 1 and CatSper 2 genes by lead and mercury.

In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated. A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25 mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR. Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (-0.01 ±â€¯0.24, -0.007 ±â€¯0.52 vs. 1 ±â€¯0.50, P = 0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (-0.24 ±â€¯2.28, -4.49 ±â€¯4.86 vs. 1 ±â€¯0.50, P = 0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93 ±â€¯0.17, 1.54 ±â€¯0.17 vs. 0.51 ±â€¯0.11; P ≤ 0.000). The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.

Crosstalk between SHH and stemness state signaling pathways in esophageal squamous cell carcinoma.

The expression of GLI1 as a downstream gene of sonic hedgehog (Hh) pathway, studied in a variety of cancers including esophageal squamous cell carcinoma (ESCC). However, the interaction of Hh with other developmental pathways needs to be elucidated. In this study, we aimed to investigate the correlation of GLI1 expression with transcription factors (TFs) of stem cell signaling pathways, and their association with clinico-pathological data of ESCC. Using real-time PCR, we assessed the expression of GLI1 mRNA in 49 ESCC patients, and analyzed the correlation between GLI1 and selected TFs. The results showed overexpression of GLI1 in ESCC tissues in significant correlation with lymph node metastasis. The GLI1 up-regulation was also correlated to the SOX2 and SIZN1 (Smad-interacting zinc finger protein) expression. These correlations may confirmed the role of GLI1 in crosstalk among different cell signaling pathways in ESCC. To our knowledge, this is the first study to demonstrate the correlation of GLI1 expression with stemness marker and BMP signaling in ESCC.

A 14-Year-Old Boy with Torsion of the Epididymal Cyst.

Epididymal cyst is a benign mass in the scrotum that is relatively common in adults but it is rare in children. In routine experience the treatment of such cysts is conservative. Torsion of these cysts is extremely rare and the diagnosis is made by exploration of the scrotum. Our patient was a 14-year-old boy who has been referred to hospital with scrotal pain followed by a minor trauma 3 days ago. Exploration of the scrotum to rule out testicular rupture was performed and a large black cyst connected to the head of the epididymis with 720-degree rotation was found. The cyst was resected and pathologic examination revealed an acquired epididymal cyst (spermatocele). The patient has normal physical exam after 3 months' follow-up.

Role of SALL4 in the progression and metastasis of colorectal cancer.

BACKGROUND: Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuance of this trait. SALL4 is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in colorectal tumor cells. To determine this level and probable clinicopathological consequences, its expression was analyzed. METHODS: SALL4 expression in fresh tumoral and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction (PCR). RESULTS: Greater than a two-fold increase in SALL4 expression was detected in 87% of tumors vs. normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately-differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger than older patients with tumor cells in stages I and II (P < 0.05). CONCLUSIONS: These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent advancement of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 may have a role in progression, development and maintenance of colorectal cancers.

Association of Epstein Barr virus deoxyribonucleic acid with lung carcinoma.

CONTEXT: Lung cancer is the leading cause of cancer death worldwide. In addition to smoking, a variety of other contributing factors, including viral infection, have been suggested in tumorigenesis. Epstein Barr virus (EBV), which is linked to various malignancies, seems to be a good candidate. AIMS: The aim of this study was to investigate the association of EBV with lung carcinomas. SETTINGS AND DESIGN: A total number of 90 formalin fixed paraffin embedded lung tissue samples including 48 cases of lung cancers (18 squamous cell carcinomas [SCCs], 18 adenocarcinomas and 12 small cell carcinomas) and 42 non-tumoral samples (control group), were retrieved from the pathology archive. MATERIALS AND METHODS: Following deoxyribonucleic acid extraction, polymerase chain reaction (PCR) was performed using an EBV-Eph PCR kit. The positive cases were studied immunohistochemically for the expression of EBV-late membrane protein-1 (EBV-LMP-1) in tumoral tissues. STATISTICAL ANALYSIS USED: The t-test and Fisher exact test were used and P < 0.05 was considered statistically significant. RESULTS: Five of our cases, including four SCCs and one adenocarcinoma and two control samples showed a positive reaction in PCR. All positive tumoral cases showed diffuse staining with LMP-1 in immunohistochemistry. CONCLUSIONS: We found a significant difference in the presence of the EBV genome in cases of lung SCC compared to other lung lesions (P = 0.02). According to our data, EBV is not at major play in the non-lymphoepithelioma-like cancers of the lung in general, but may have a role in the tumorigenesis of some lung SCCs.