Reproductive toxicity of cadmium (Cd) as an environmental toxicant has been proved in animals and humans. Exposure to Cd impairs testes organs and can reduce male fertility. The present study was ...designed to investigate the spectrum of histopathological changes in testicular tissue focusing on Sertoli cells in rats following Cd intoxication.
In the present experiment, acute testicular toxicity was induced by an intraperitoneal injection of 1.2 mg/kg CdCl
to the animals in the test group, while the control group received normal saline. After 52 days, the animals were euthanized, and testicular tissue was stained by Hematoxylin and Eosin. In addition, immunohistochemical staining was performed on Sertoli cells for Wilms' Tumor, Melan-A, and CD99 to evaluate histopathological changes.
Cd caused significant alterations in seminiferous tubules with varying effects on the patterns of spermatozoa production. These histopathological changes were significantly higher in the Cd group, compared to the control group.
The Cd-induced stepwise spectrum changes included sloughing, disorganization, hypospermatogenesis, spermatic cell arrest, germ cell hypoplasia, Sertoli cell-only pattern, fibro-hyalinized seminiferous tubules, and calcification. Sertoli cells accumulated and created multinucleated giant cells in the seminiferous tubules during the atrophic process, which could be dependent upon Sertoli cells viability and function.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction: Lung cancer (LC) is the most common type of cancer and causes of death among males. This study aims to estimate the survival rate of lung cancer patients by employing the benefits of ...Bayesian modeling in determining factors affecting the survival of lung cancer in Kerman province, Iran.
Methods: We conducted a historical cohort study of 195 patients with lung cancer from 2016 to 2018. In this study, we used linear dependent Dirichlet process (LDDP), and employed some results of the previous study as informative prior for better estimation.
Results: Of the 195 patients, 160 died. The mean age of patients at the time of diagnosis was 62.43±12.55. The median survival time of patients was 10.4 months. Men accounted for 75.9% of the total patients. One, two, and three-year survival rate was 44.5%, 22.9%, and 16.4%, respectively. The multivariable model results showed that treatments were significant. Other variables had no significant effect.
Conclusion: Our study highlights the importance of prompt diagnosis and appropriate treatment in improving the survival rate of lung cancer patients. We found that patients who received at least one usual lung cancer treatment, such as chemotherapy, radiation therapy, or surgery, had higher survival rates compared to those who did not receive any treatment. While our study has some limitations, such as its retrospective design, our use of Bayesian modeling techniques allowed us to effectively incorporate prior information from previous studies to improve estimation accuracy.
The present investigation was conducted to evaluate the vascular-toxicity of empagliflozin (EMP) in embryonic vasculature. Firstly, the vascular-toxicity of the drug as well as its interaction with ...apoptotic regulator proteins was predicted
via in silico
approach. In the next step, the apoptotic-signaling pathway in embryonic vasculature was evaluated using a chick’s YSM model.
In silico
simulation confirmed vascular-toxicity of EMP. There was also an accurate affinity between EMP, Bax and Bcl-2 (−7.9 kcal/mol). Molecular dynamics assay revealed complex stability in the human body conditions. Furthermore, EMP is suggested to alter Bcl-2 more than BAX. Morphometric quantification of the vessels showed that the apoptotic activity of EMP in embryonic vasculature was related to a marked reduction in vessel area, vessel diameter and mean capillary area. Based on the qPCR and immunohistochemistry assays, enhanced expression level of BAX and reduced expression level of Bcl-2 confirmed apoptotic responses in the vessels of the YSM. We observed that induction of an apoptotic signal can cause the embryonic defect of the vascular system following EMP treatment. The acquired data also raised suspicions that alteration in apoptotic genes and proteins in the vasculature are two critical pathways in vascular-toxicity of EMP.
Basal cell carcinoma (BCC) manifests different dermoscopic patterns in individuals with dark skin complexion compared to those with fair skin types. This study aimed to investigate the diagnostic ...utility of dermoscopy in discerning superficial BCC from other types of BCC, specifically in patients with dark skin complexion.
This cross-sectional study focuses on patients diagnosed with BCC who were referred for skin biopsy between July 2020 and September 2022. Initially, the demographic characteristics of patients, clinical attributes of lesions, and pathological sub-types of BCC were documented. Subsequently, videodermoscopy was employed to capture comprehensive views and dermoscopic images of the lesions. Univariate logistic regression analysis was then utilized to assess the reliability of dermoscopic structures in distinguishing superficial BCC from other BCC types. Last, the study evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of dermoscopy in the differentiation of superficial BCC from other BCC sub-types.
The study enrolled 49 patients diagnosed with BCC, with a mean age of 66.22 ± 10.41 years. The most prevalent pathological sub-type observed was nodular (53.1%). Dermoscopy exhibited a higher specificity compared to the naked eye in the differentiation of superficial BCC from other types (55% vs. 35%, respectively). Univariate analysis revealed a significant association between spoke-wheel structures and superficial BCC (
= 0.02, odds ratio = 7.2, 95% confidence interval = 1.35-38.32).
Dermoscopy exhibited superior specificity compared to the naked eye in differentiating superficial BCC from other BCC types. Notably, the spoke-wheel structure demonstrated the most robust correlation with superficial BCC.
Cervical intraepithelial neoplasia (CIN) is a dysmaturation process in squamous cells in epithelial layer, which highly increases the risk of developing cervical cancer. The aim of this study was to ...compare the expression of three biomarkers, p16, p63, and CK17 in patients with CIN and in those with atypical squamous metaplasia (ASM).
In this study, 100 patients underwent a colposcopy-guided cervix biopsy. Immunostaining for the biomarkers was undertaken on tissue samples presented with ASM (n=50) and CIN (n=50).
A significant increase in immunostaining for CK7, P63, and P16 in patients with CIN was found compared to ASM subjects.
Expression of CK17, P63, and P16 in CIN varied from those in ASM. Those biomarkers could be reliable factors to distinguish ASM from CIN; however, all the biomarkers could differentiate CIN from its mimics due to their high degree of sensitivity and specificity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Colorectal cancer (CRC), like other cancers, needs faster and more accurate identifications. A well-timed prognosis of CRC could be an important turning point in the survival of patients. ...Supplementary signs, such as long non-coding RNAs (lncRNAs), could be helpful for this purpose. A new possible biomarker for CRC identification is introduced by this study.
RNA extraction was performed by the RNX-Plus solution for 64 tumor and non-tumor tissues. Complementary DNAs (cDNAs) were synthesized, and quantitative real-time PCR was performed for relative expression level measurement and the data was analyzed statistically using the Prism 6 software. For Small nucleolar host gene 6 knockdown, siRNA was designed based on Reynolds rules. The cells were cultured in their appropriate media, and the siRNA-lipofectamine complex was formed. The transfection complex was presented for sw48, sw480, and sw1116 as CRC cells with different grades. After transfection, the SNHG6/β actin ratio was determined. Then, the distribution of siRNA-treated cells was determined by the Partec flow cytometer instrument and analyzed by the FloMax software.
SNHG6 was more expressed in CRC tumors than non-tumor tissues. In tumor tissues, SNHG6 upregulation and tumors' grade progression were concurrent. SNHG6 was upregulated in cases with lymphovascular invasion than in cases with perineural invasion. The knockdown of SNHG6 conduced to G1 arrest in CRC cells, more noticeably in high-grade ones.
SNHG6 could be applied as a consideration to differentiate tumor and non-tumor tissues and grade definition in colorectal malignancies, and it could participate in colorectal tumor formation as a cell cycle progressive factor.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Cystic echinococcosis (CE) caused by the cestode
is a disease of worldwide public health and economic importance. The determinants and underlying cellular mechanisms of CE development and fate in ...intermediate hosts are largely unknown. Hormones and cytokines such as insulin and BMP-4 are the key players in the development, differentiation, and apoptosis. In this study, we evaluated the long term natural history of
microcysts in an vitro setting and the molecular and morphological changes induced by the growth factors, insulin and BMP4 during the development of metacestode stage of
.
protoscoleces were cultivated and the parasite development was followed in the long term mono-phasic culture for 105 days and the morphometric, molecular and immunohistochemical changes were evaluated, including the microcysts number and size, microcysts development and deformation rates as well as the markers of calcification (Alizarin Red staining) and apoptosis (BAX, BCL2, Caspase-3, Caspase-8 and TNF-α expression) in the microcysts. Also the biological, histological and molecular consequences of insulin and BMP-4 treatment on the parasite development were evaluated.
Insulin and BMP-4 treatment of microcysts resulted in significant increase in microcyst formation, increased size, reduced apoptosis and deformation of the microcysts. Alizarin red staining of the microcysts treated with the insulin and BMP-4 confirmed that calcium deposition is significantly lower than the untreated microcysts. Also Alizarin Red staining and Immunohistochemistry of the microcysts indicates that calcium accumulation in deformed microcysts is higher than the normal ones on day 105. The microcysts began to wrinkle and the germinal layer was partially detached from the laminated layer on day 84.
Results of the present study suggest that the degenerative changes in hydatid cysts can be slowed down by insulin and BMP-4, indicating that cellular factors and host hormones could contribute to the longevity of hydatid cysts. Significant evidences are provided suggesting that the microcysts cultivated
can undergo calcification and apoptotic processes similar to what have been observed in the natural hydatid infection in the intermediate hosts.
Pulmonary arterial hypertension (PAH) is a severe disease that leads to pulmonary vascular remodeling characterized by a rise in pulmonary vascular resistance and pressure. We assessed the effects of ...an herbal compound, berberine (BB), and some related mechanisms on PAH in rats. Male Wistar rats were assigned to seven groups: control, monocrotaline (MCT), MCT+vehicle, and MCT+BB (with doses of 10, 20, 30, and 40 mg/kg) groups. Three weeks after induction of PAH by MCT, treatment groups received daily intraperitoneal injections of vehicle or BB for 3 weeks. On Day 43, the right ventricular systolic pressure (RVSP, as an index of pulmonary arterial pressure) and the ratio of RV to LV+septum weight (as RV hypertrophy index, right ventricle hypertrophy RHVI) were measured. Inflammatory and oxidative stress indices and histopathology of the lungs were also assessed. RVSP (89.4 ± 8.2 vs. 23 ± 3.3), RVHI (0.63 ± 0.08 vs. 0.26 ± 0.04), and lung inflammatory cytokines TNF‐α (2.03 ± 0.25 vs. 1.21 ± 0.3) and IL‐6 (8.8 ± 0.59 vs. 6.3 ± 0.95) significantly increased in the MCT group compared to the control group. MCT also raised the level of Malondialdehyde (0.11 ± 0.01 vs. 0.09 ± 0.01) and diminished total antioxidant capacity (6.5 ± 0.51 vs. 8.3 ± 0.62), the activity of superoxide dismutase (1.19 ± 0.22 vs. 1.93 ± 0.2), glutathione peroxidase (0.02 ± 0.002 vs. 0.03 ± 0.005), catalase (2.1 ± 0.29 vs. 2.8 ± 0.20) and Bax/Bcl‐2 ratio (0.41 ± 0.07 vs. 0.61 ± 0.09) in the lungs. Treatment with BB significantly recovered all of these alterations. BB ameliorated pulmonary vascular remodeling by decreasing inflammation and fibrosis and increasing apoptosis and antioxidant/oxidant balance. Therefore, this herbal derivative may be considered a therapeutic goal against PAH.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
BACKGROUND & OBJECTIVEEarly detection of malignancies in the serous fluids has been remained an issue. A classic diagnostic tool for the ascites and pleural effusions is cytologic study (morphology) ...with approximately 98% specificity for the detection of cancer cells. This study aimed to evaluate the diagnostic value of three complementary markers in the serosal fluids of patients with malignant cytology and suspected cases. METHODSSeventy two patients with serosal effusion treated in three teaching hospitals were studied. The cases underwent a diagnostic workup to determine the pleural effusion malignancy and etiologies. Complementary markers, including CEA, CA15-3, and CA125 were measured in serosal fluids of three categories of benign, suspicious, and malignant. The study was carried out by Chemiluminescence immunoalayzer. The morphologies were re-evaluated by a consulting Cytopathologist. RESULTSOf 72 serosal fluid specimens, 41 (56.9%) were related to pleural effusion and 31 (43.1%) were related to ascites. The sensitivity of CEA, CA125, and CA15-3 biomarkers were 64, 84, and 68%, respectively, and the specificity of each test was 100, 86, and 96%, respectively. This was statistically achieved for the combination of the area of markers below the curve (AUC), 0.93 and 90% sensitivity and 91% specificity. CONCLUSIONThe results suggest that complementary CA125, CA15-3, and CEA markers assayed with well-developed immunoassay method might be useful in the differentiation between malignant and benign effusions while combined with conventional cytology. CA125 yielded a significant correlation between cytomorphology and biomarkers based on the correlation coefficient analysis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The advancements in nanoscience have brought attention to the potential of utilizing nanoparticles as carriers for oral insulin administration. This study aims to investigate the effectiveness of ...synthesized polymeric mesoporous silica nanoparticles (MSN) as carriers for oral insulin and their interactions with insulin and IR through in-silico docking. Diabetic rats were treated with various MSN samples, including pure MSN, Amin-grafted MSN/PEG/Insulin (AMPI), Al-grafted MSN/PEG/Insulin (AlMPI), Zinc-grafted MSN/PEG/Insulin (ZNPI), and Co-grafted MSN/PEG/Insulin (CMPI). The nanocomposites were synthesized using a hybrid organic-inorganic method involving MSNs, graphene oxide, and insulin. Characterization of the nanocomposites was conducted using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). In vivo tests included the examination of blood glucose levels and histopathological parameters of the liver and pancreas in type 1 diabetic rats. The MSN family demonstrated a significant reduction in blood glucose levels compared to the diabetic control group (p < 0.001). The synthesized nanocomposites exhibited safety, non-toxicity, fast operation, self-repairing pancreas, cost-effectiveness, and high efficiency in the oral insulin delivery system. In the in-silico study, Zn-grafted MSN, Co-grafted MSN, and Al-grafted MSN were selected. Docking results revealed strong interactions between MSN compounds and insulin and IR, characterized by the formation of hydrogen bonds and high binding energy. Notably, Co-grafted MSN showed the highest docking scores of −308.171 kcal/mol and −337.608 kcal/mol to insulin and IR, respectively. These findings demonstrate the potential of polymeric MSN as effective carriers for oral insulin, offering promising prospects for diabetes treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP