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Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type., Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters., Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence., Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy., Competing Interests: None., (© 2024.)

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown origin with limited treatment options and poor prognosis. The encouraging findings from preclinical investigations utilizing mesenchymal stem cells (MSCs) indicated that they could serve as a promising therapeutic alternative for managing chronic lung conditions, such as IPF. The objective of this study was to compare the efficiency of bone marrow-derived MSCs (BM-MSCs) versus prednisolone, the standard anti-inflammatory medication, in rats with bleomycin (BLM)-induced lung fibrosis. Four groups were created: a control group, a BLM group, a prednisolone-treated group, and a BM-MSCs-treated group. To induce lung fibrosis, 5 mg/kg of BLM was administered intratracheally. BLM significantly increased serum levels of pro-inflammatory cytokines and oxidative stress markers. The disturbed lung structure was also revealed by light and transmission electron microscopic studies. Upregulation in the immune expression of alpha-smooth muscle actin, transforming growth factor beta-1, and Bax was demonstrated. Interestingly, all findings significantly regressed on treatment with prednisolone and BM-MSCs. However, treatment with BM-MSCs showed better results than with prednisolone. In conclusion, BM-MSCs could be a promising approach for managing lung fibrosis., Competing Interests: Conflict of Interest The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGD AF ), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis., Methods: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue., Results: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGD AF , 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGD AF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGD AF , FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGD AF , FASL, and BCL2 in combination than for individual measurements., Conclusion: Combining short AGD AF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis., (© 2024 International Federation of Gynecology and Obstetrics.)

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1β, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects., (© 2024 John Wiley & Sons Ltd.)

Background: Inflammatory bowel disease is an autoimmune disease that affects the gut. T. spiralis larvae (E/S Ags) loaded on calcium-benzene-1,3,5-tricarboxylate metal-organic frameworks (Ca-BTC MOFs) were tested to determine whether they might prevent or cure acetic acid-induced murine colitis. Methods: T. spiralis larvae E/S Ags/Ca-BTC MOFs were used in prophylactic and therapeutic groups to either precede or follow the development of murine colitis. On the seventh day after colitis, mice were slaughtered. The effect of our target antigens on the progress of the colitis was evaluated using a variety of measures, including survival rate, disease activity index, colon weight/bodyweight, colon weight/length) ratios, and ratings for macroscopic and microscopic colon damage. The levels of inflammatory cytokines (interferon-γ and interleukin-4), oxidative stress marker malondialdehyde, and glutathione peroxidase in serum samples were evaluated. Foxp3 T-reg expression was carried out in colonic and splenic tissues. Results: T. spiralis larvae E/S Ags/Ca-BTC MOFs were the most effective in alleviating severe inflammation in murine colitis. The survival rate, disease activity index score, colon weight/length and colon weight/bodyweight ratios, and gross and microscopic colon damage scores have all considerably improved. A large decrease in proinflammatory cytokine (interferon-γ) and oxidative stress marker (malondialdehyde) expression and a significant increase in interleukin-4 and glutathione peroxidase expression were obtained. The expression of Foxp3+ Treg cells was elevated in colonic and splenic tissues. Conclusion: T. spiralis larvae E/S Ags/Ca-BTC MOFs had the highest anti-inflammatory, antioxidant, and cytoprotective capabilities against murine colitis and might be used to develop new preventative and treatment strategies.

Triphenyltin chloride (TPT-Cl) is an organometallic organotin. This study aimed to investigate the role of trigonelline (TG) along with the impact of TPT withdrawal on the testicular toxicity induced by TPT-Cl. Thirty-six adult male albino rats were divided into control, TG (40 mg/kg/day), TPT-Cl (0.5 mg/kg/day), TG + TPT-Cl, and recovery groups. Animals were daily gavaged for 12 weeks. Both TG and TPT-Cl withdrawal improved TPT-Cl-induced testicular toxicity features involving testis and relative testis weight reduction, luteinizing hormone, follicular stimulating hormone, and sex hormone-binding globulin elevation, reduction of inhibin B, free testosterone levels, and sperm count reduction with increased abnormal sperm forms. Moreover, both TG and TPT-Cl withdrawal reduced inflammatory activin A, follistatin, tumor necrosis factor α, interleukin-1β, and proapoptotic Bax and elevated antiapoptotic Bcl2 in testicular tissues mediated by TPT-Cl. TG and TPT-Cl withdrawal restored the excessive autophagy triggered by TPT-Cl via elevation of mTOR, AKT, PI3K, and P62/SQSTM1 and reduction of AMPK, ULK1, Beclin1, and LC3 mRNA gene expressions and regained the deteriorated testicular structure. In conclusion, TG and TPT-Cl withdrawal had an ameliorative role in partially reversing TPT-Cl-induced testicular toxicity. However, the findings indicated that the use of TG as an adjunctive factor is more favorable than TPT-Cl withdrawal, suggesting the capability of the testis for partial self-improvement., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProEx TM C, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics., Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProEx TM C, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method., Results: The expression of VEGF, hTERT, and ProEx TM C was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively)., Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProEx TM C is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Background: Colorectal cancer is considered the third most prevalent cancer in both sexes. Immune checkpoint receptors that regulate T-cell response, stimulation, and development include lymphocyte activating gene 3 (LAG-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and T-cell immunoglobulin and mucin domain 3 (Tim-3). In addition, they are crucial for the advancement of cancer and tumor immune escape., Objective: This work's aim was to assess the immunohistochemistry expression of Tim-3, CTLA-4, and LAG-3 in cancer cells and tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) and the correlation between these markers and clinicopathological variables and survival data., Methods: This study involved 206 CRC specimens processed for CTLA-4, LAG3, and TIM-3 immunohistochemistry and correlated with the clinicopathological and survival parameters of the patients., Results: High CTLA-4 epithelial expression was highly related to the old age group, large tumor size, low tumor-stroma ratio (TSR), high grade, advanced stage, the presence of distant metastasis (DM), perineural invasion (PNI), necrosis, lymphovascular invasion (LVI), relapse, mortality, overall survival (OS), and disease-free survival (DFS), while negative CTLA-4 TILs expression was highly linked with the presence of gross perforation, low TSR, high tumor budding (TB) score, high grade, advanced stage, the existence of lymph node (LN) metastasis, DM, necrosis, LVI, PNI, DFS, mortality, and OS. Positive LAG-3 TILs expression was highly correlated with large tumor size, gross perforation, low TSR, high TB score, high grade, advanced phase, the presence of LN, necrosis, LVI, PNI, relapse DFS, mortality, and OS. High Tim-3 epithelial expression was extremely linked with low TSR, advanced phase, the presence of LN, LVI, PNI, relapse, DFS, mortality, and OS, while positive Tim-3 TILs expression was related to gross perforation, low TSR, high TB score, advanced stage, the presence of LN, DM, necrosis, relapse, DFS, mortality, and OS., Conclusions: The patients' poor prognosis may be related to the immunohistochemistry expression of LAG-3, Tim-3, and CTLA-4 in CRC cancer tissue and TILs. Poor patient consequences can result from the CTLA-4, Tim-3, and LAG-3 co-expression, but CTLA-4 TILs' expression of these proteins may inhibit the growth of tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and -negative classical Hodgkin lymphoma (CHL)., Methods: A prospective cohort study was conducted from 2017 to 2022 at the Faculty of Medicine, Zagazig University Hospital (Zagazig, Egypt). Biopsy samples of 64 patients with CHL were divided into EBV-positive and EBV-negative groups. The expression levels of mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, COX-2) and the end product of proteins (PD-L1, Bcl-xL, COX-2) were determined and compared with clinicopathological and prognostic parameters. Data were analyzed using the Chi square test and Kaplan-Meier estimate., Results: EBV-positive CHL patients were significantly associated with positive expression of mRNAs molecules (P<0.001) and the end product of proteins (P<0.001) for the JAK/STAT and NF-κB pathways, B-symptoms (P=0.022), extra-nodal involvement (P=0.017), and advanced stage of CHL (P=0.018). These patients were more susceptible to cancer progression, higher incidence of relapse (P=0.008), poor disease-free survival rate (P=0.013), poor overall survival rate (P=0.028), and higher mortality rate (P=0.015)., Conclusion: Through the activation of JAK/STAT and NF-κB signaling pathways, EBV-positive CHL is associated with poor clinicopathological parameters, higher incidence of disease progression, relapse, and poor overall survival. A preprint of this manuscript is available on research square (doi: 10.21203/rs.3.rs-1857436/v1)., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Background: It will be important to understand the molecular pathways of gastric cancer (GC) occurrence and progression, thus detecting predictive and prognostic biomarkers of GC. Pyrroline-5-carboxylate reductase 1 (PYCR1) was upregulated in many cancers, suggesting its possible roles in carcinogenesis and tumor metastases. Barrier-of-autointegration factor 1 (BANF1) is a protein family that plays essential roles in maintaining the integrity of an intact cellular genome. Rho-GTPs are molecular switches that control many signal transduction pathways in normal cells, including 3 subgroups from 1 to 3 (DLC1-3). DLC-3, known as StAR-related lipid transfer domain protein 8 (STARD8), and its role in cancers were not sufficiently studied. The study aimed to investigate the significance of PYCR1, BANF1, and STARD8 protein expression in GC tissues and normal gastric mucosa retrieved from patients with GC to detect prognostic roles of expression., Patients and Methods: Specimens were collected from 100 patients with gastric carcinoma. After the application of the inclusion criteria of the study, we prepared 100 paraffin blocks from samples of the 100 included patients; each block included samples from gastric carcinoma and adjacent non-neoplastic gastric mucosa. We assessed the expression of PYCR1, BANF1, and STARD8 using immunohistochemistry in all studied samples. We followed patients for the detection of disease progression and survival rates. We correlate PYCR1, BANF1, and STARD8 expression with clinical, pathologic, and prognostic parameters., Results: Overexpression of PYCR1 and BANF1 and decreased expression of STARD8 was found in gastric carcinoma tissues than adjacent non-neoplastic gastric mucosa ( P <0.001), and was positively associated with high grade ( P =0.006), depth of tumor invasion, presence of lymph nodes metastases and advanced stage ( P =0.001), high incidence of GC progression, recurrence, unfavorable disease-free survival ( P =0.003) and unfavorable overall survival rates ( P <0.001). Thus, it was revealed that; in univariate and multivariate analyses, levels of PYCR1, BANF1, and STARD8 are associated with the overall survival rate of GC patients., Conclusions: We showed that overexpression of PYCR1 and BANF1 and decreased expression of STARD8 in GC tissues was associated with poor prognosis and GC progression., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism., Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant., Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001)., Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Trichinellosis is a re-emerging worldwide foodborne zoonosis. Oxidative stress is one of the most common detrimental effects caused by trichinellosis. In addition, Trichinella infection poses an infinite and major challenge to the host's immune system. Resistance and side effects limit the efficiency of the existing anti- trichinella medication. Given that concern, this work aimed to investigate the anti-helminthic, antioxidant, anti-inflammatory and immunomodulatory effects of resveratrol and zinc during both phases of Trichinella spiralis infection. Sixty-four Swiss albino mice were divided into four equal groups: non-infected control, infected control, infected and treated with resveratrol, and infected and treated with zinc. Animals were sacrificed on the 7th and 35th days post-infection for intestinal and muscular phase assessments. Drug efficacy was assessed by biochemical, parasitological, histopathological, immunological, and immunohistochemical assays. Resveratrol and zinc can be promising antiparasitic, antioxidant, anti-inflammatory, and immunomodulatory agents, as evidenced by the significant decrease in parasite burden, the significant improvement of liver and kidney function parameters, the increase in total antioxidant capacity (TAC), the reduction of malondialdehyde (MDA) level, the increase in nuclear factor (erythroid-derived 2)-like-2 factor expression, and the improvement in histopathological findings. Moreover, both drugs enhanced the immune system and restored the disturbed immune balance by increasing the interleukin 12 (IL-12) level. In conclusion, resveratrol and zinc provide protection for the host against oxidative harm and the detrimental effects produced by the host's defense response during Trichinella spiralis infection, making them promising natural alternatives for the treatment of trichinellosis.

Valproic acid (VPA) is a commonly used drug for management of epilepsy. Prolonged VPA administration increases the risk of hepatotoxicity. Liraglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist that act as a novel antidiabetic drug with broad-spectrum anti-inflammatory and antioxidant effects. This study tested the protective effect of liraglutide against VPA-induced hepatotoxicity elucidating the possible underlying molecular mechanisms. Forty adult male rats were allocated in to four equally sized groups; Group I (control group) received oral distilled water and subcutaneous normal saline for 2 weeks followed by subcutaneous normal saline only for 2 weeks. Group II (liraglutide group) received subcutaneous liraglutide dissolved in normal saline daily for 4 weeks. Group III (valproic acid-treated group) received sodium valproate dissolved in distilled water for 2 weeks. Group IV (Combined valproic acid & liraglutide treated group) received valproic acid plus liraglutide daily for 2 weeks which was continued for additional 2 weeks after valproic acid administration. The hepatic index was calculated. Serum AST, ALT, GGT, and ALP activities were estimated. Hepatic tissue homogenate MDA, GSH, SOD, HMGB1, MAPK, RIPK1, and RIPK3 levels were evaluated using ELISA. However, hepatic RAGE and MLKL messenger RNA expression levels using the QRT-PCR technique. Hepatic NF-κB and TNF-α were detected immunohistochemically. Results proved that liraglutide coadministration significantly decreased liver enzymes, MDA, HMGB1, MAPK, RIPK1 RIPK3, RAGE, and MLKL with concomitant increased GSH and SOD in comparison to the correspondent values in VPA-hepatotoxicity group. Conclusions: Liraglutide's protective effects against VPA-induced hepatotoxicity are triggered by ameliorating oxidative stress, inflammation, and necroptosis., (© 2023 John Wiley & Sons Ltd.)

Microplastics (MPs) have become a worldwide issue because of their persistence in marine organisms, their accumulation in the food chains, and their inevitable human exposure. Silymarin is a therapeutic agent used in the treatment of multiple liver diseases. The study aimed to explore the potential therapeutic effect of 2 weeks of silymarin treatment against the effects of two sizes of 1 and 5 μm of polystyrene microplastic particles (PS-MPs) on the liver after 6 weeks of the study period. Animals were divided into negative and positive control, silymarin group (200 mg/kg), PS-MP groups of 1 and 5 μm size (0.02 mg/kg), 1 μm size PS-MPs + silymarin group, and 5 μm size PS-MPs + silymarin group, animals were treated once daily by oral gavage. The study revealed that hepatotoxicity induced by two diameters of PS-MPs with marked destructive effects of 1 μm size greater than that of 5 μm size and the effective therapeutic role of silymarin in improving PS-MPs caused hepatotoxic injury, particularly with 5 μm PS-MPs size; through regression of liver pathology (hepatic cell lysis, inflammation, fibrotic changes, and collagen deposition), restoring ultrastructure morphology (mitochondrial destruction and accumulation of lipid droplets accumulation). It improved liver function by reducing serum AST, ALT, LDH, total cholesterol, and triglycerides. It also reduced oxidative stress by reducing serum MDA, increasing TAC, down-regulation of iNOS, and up-regulation of Nrf2 and HO-1 hepatic gene expression. Furthermore, it relieved pyroptosis by negatively regulating the expression of the NLRP3, caspase-1, and IL-1β hepatic gene expression. The results suggested silymarin's therapeutic effects in treating PS-MPs-induced hepatotoxic injury and recommended its use as a postexposure treatment for a longer duration.

The food color metanil yellow (Myl) is hazardous to several body systems. Evening primrose oil (EPO) was reported to have anti-inflammatory and anti-oxidant properties. The present work investigated the impact of Myl on the hepatic structure and function of rats and evaluated the protective effect of EPO. Forty adult male rats were divided into four groups: control, EPO (5 g/kg/day), Myl (200 mg/kg/day), and EPO- Myl group. Myl significantly increased liver enzymes, advanced glycation end products (AGE), oxidative stress parameters, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB), and inducible nitric oxide synthase (iNOS). Blood vessels in the liver were dilated and congested, with cellular infiltration around them and associated with fibrosis. The hepatocytes were vacuolated and had dark nuclei. The immunohistochemical expression of iNOS, glial fibrillary acidic protein (GFAP), and Bax was significantly elevated. Ultrastructurally, the hepatocytes showed lipid droplets, irregular condensed nuclei with widened perinuclear space, dilated rER, mitochondria with destructed cristae, and multiple vacuoles. Dilated congested blood sinusoids and collagen fiber bundles were seen between hepatocytes. Interestingly, these alterations were less pronounced in rats co-administrated with EPO and Myl. In conclusion, EPO can protect liver against the toxic effects of Myl due to its anti-inflammatory and anti-oxidant activities.

Perfluorooctane sulfonate (PFOS) has harmful impacts on various organs, including the intestine. Lemongrass essential oil (LGEO) has anti-inflammatory, anti-oxidant, antibacterial, and immunomodulatory effects. This study investigated the impact of PFOS on the mucosa of the jejunum of rats and evaluated LGEO's protective impact. Four groups of rats were created: control, LGEO (100 mg/kg/day), PFOS (5 mg/kg/day), and LGEO-PFOS group. The agents were given orally for 28 days. Oxidative stress parameters, pro-inflammatory cytokines, and caspase-3 were measured in jejunal homogenates. Rat jejunal sections were evaluated histologically (light and electron microscopic examination) and immunohistochemically [for tumor necrosis factor-α (TNF-α), Proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX2), and Bcl2]. PFOS significantly elevated oxidative stress, pro-inflammatory cytokines, caspase-3, and gene expression of nuclear factor kappa B (NF-kB) and inducible nitric oxide synthetase (iNOS). The disturbed architecture of jejunal villi and crypts was demonstrated. Immunohistochemically, a significant rise in TNF-α, PCNA, and COX2 and a significant decrease in Bcl2 expression were revealed compared to control group. Further ultrastructural alterations included dilated RER, mitochondria with destroyed cristae, vacuolated cytoplasm, and shrunken condensed nuclei of enterocytes. LGEO treatment significantly reduced these harmful effects. LGEO protected against PFOS-induced jejunal damage by reducing the oxidative, inflammatory, and apoptotic impacts., Competing Interests: Conflict of interest The authors declare that they are not involved in any conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Alzheimer's disease (AD) is one of the most common types of dementia among neurodegenerative disorders characterized by attention deficits and memory loss. Panax ginseng is a traditional Chinese herbal remedy that has been employed for millennia to manage dementia linked with aging and memory impairment. Ginsenoside Rb1 is one of Panax ginseng's most abundant components. The present work evaluated the neuroprotective effects of ginsenoside Rb1 on the cerebral cortex of AlCl 3 -induced AD in adult male albino mice. Forty male mice were alienated arbitrarily into; control group, ginsenoside Rb1 group (70 mg/kg/day), AlCl 3 group (50 mg/kg/day), and ginsenoside Rb1-AlCl 3 group that received ginsenoside Rb1 one hour before AlCl 3 . Oxidative stress parameters, Amyloid β (Aβ) and phosphorylated tau protein, and acetylcholine esterase (AChE) activity were measured. Cerebral cortex sections were evaluated histologically by light microscopic examination and immunohistochemistry. AlCl 3 -induced memory impairment, Aβ and phosphorylated tau protein accumulation, and AChE elevation. Moreover, histopathological alterations in the cerebral cortex were reported in the form of irregular shrunken neurons and the surrounding neuropil showed vacuolation. Some neurons appeared with darkly stained nuclei, others had faintly stained ones. The synaptophysin expression was significantly decreased, while the expression of cleaved caspase-3, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were significantly elevated. It's interesting to note that these changes were attenuated in mice pretreated with ginsenoside Rb1. Collected data indicated that ginsenoside Rb1 showed a potential neuroprotective effect against cerebral cortex changes caused by AlCl 3 via suppression of Amyloid β and phosphorylated tau protein formation, oxidative stress correction, anti-apoptotic effect, and by minimizing gliosis., Competing Interests: Conflict of interest The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a mixed endocrine/metabolic/reproductive disorder in women of reproductive age. Sesame oil (SO) contains sesame lignans & vitamin E with broad-spectrum antioxidant and anti-inflammatory effects. This study investigates the ameliorative effect of SO on experimentally induced PCOS and elucidates the possible molecular mechanisms with a deeper focus on the different signaling pathways involved. The study was carried out on 28 nonpregnant female Wister albino rats that were divided into four equal groups; Group I (control group) received oral 0.5% wt/vol carboxymethyl cellulose daily. Group II (SO group): orally administered SO (2 mL/kg body wt./day) for 21 days. Group III (PCOS group) received letrozole daily, 1 mg/kg, for 21 days. Group IV (PCOS + SO group): concomitantly administered letrozole and SO for 21 days. The serum hormonal and metabolic panel and the homogenate ATF-1, StAR, MAPK, PKA, and PI3K levels of the ovarian tissue were calorimetrically evaluated. However, endoplasmic reticulum (ER) stress was evaluated by ovarian XBP1 and PPAR-γ messenger RNA expression level using the qRT-PCR technique. Ovarian COX-2 was detected immunohistochemically. The results suggest that SO-treated PCOS rats showed a significantly improved hormonal, metabolic panel, inflammatory, and ER stress status with concomitant decreases in ATF-1, StAR, MAPK, PKA, and PI3K in ovarian rats compared to the correspondent values in PCOS without treatment. CONCLUSIONS: The protective effects of SO against PCOS are triggered by ameliorating regulatory proteins of ER stress, lipogenesis, and steroidogenesis through the PI3K/PKA and MAPK/ERK2 signaling cascades. SIGNIFICANCE STATEMENT: Polycystic ovary syndrome (PCOS) is the most common mixed endocrine-metabolic dysfunction among women within the reproductive period, with an estimated prevalence of 5%-26% worldwide. Doctors traditionally recommend metformin for PCOS patients. However, metformin is known to be associated with significant adverse effects and contraindications. This work aimed at shedding light on the ameliorative effect of sesame oil (SO), natural polyunsaturated fatty acids-rich oil, on the induced PCOS model. SO proved to have a marvelous effect on the metabolic and endocrine derangements in the PCOS rat model. We hoped to provide a valuable alternative treatment for PCOS patients to avoid the side effects of metformin and to help PCOS patients for whom metformin is contraindicated., (© 2023 John Wiley & Sons Ltd.)

Background & Objective: Cells of renal cell carcinoma (RCC) are resistant to the most currently used chemotherapeutic agents and targeted therapies; hence, we evaluated the expression of NEK2, JMJD4, and REST in cases of clear cell renal cell carcinoma (ccRCC) and benign adjacent tissues of kidney to detect associations between their expression and clinicopathological features, prognostic data, tumor recurrence, and survival rates., Methods: We collected 200 samples including tumoral and adjacent non-neoplastic tissues related to 100 ccRCC patients. All samples were evaluated for the expression of NEK2, JMJD4, and REST, and the patients were followed up for about 5 years. Tumor recurrence and survival data were documented and analyzed., Results: NEK2 and JMJD4 expression showed increase in ccRCC tissues ( P =0.002 and 0.006), while REST was downregulated ( P <0.001). The elevated expression of NEK2 was positively related ro the tumor size ( P =0.015), higher grades ( P =0.002), higher stages ( P =0.013), distant spread ( P =0.004), tumor recurrence, shorter progression-free survival (PFS) rate, and overall survival (OS) rate ( P <0.001). Likewise, the high expression of JMJD4 showed positive correlation with the tumor size ( P =0.047), higher grades ( P =0.003), higher stages ( P =0.043), distant spread ( P =0.001), tumor recurrence, shorter PFS rate, and OS rate ( P <0.001). Conversely, low expression of REST demonstrated positive relationship with the tumor size, higher grades, higher stages, distant spread, tumor recurrence, and shorter PFS and OS rates ( P <0.001)., Conclusion: Overexpression of NEK2 and JMJD4 and downregulation of REST may be noted in malignant renal tissues compared to benign renal tissues and may be correlated with unfavorable pathological findings, poor clinical parameters, and poor patient outcomes., Competing Interests: None.

The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11-12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Letrozole, an aromatase inhibitor, has recently been introduced as a favorable medical treatment for ectopic pregnancy. We aimed at evaluating the effects of different doses of letrozole for termination of ectopic pregnancy and study their effects on villous trophoblastic tissue. Sixty patients with undisturbed ectopic pregnancy were classified into three equal groups. Group I: the control group that contained women who underwent laparoscopic salpingectomy, Group II: patients who received letrozole (5 mg day -1 ) for 10 days, and Group III: patients who received letrozole (10 mg day -1 ) for 10 days. Subsequently, the β-hCG levels were determined on the first day and after 11 days of treatment. Group IV consisted of patients of GII and GIII; their β-hCG did not drop below 100 mIU/ml within 11 days, and underwent salpingectomy. Placental tissues from patients undergoing salpingectomy either from the control group or GIV were processed for the evaluation of estrogen (ER) and progesterone (PR) receptors, vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC-3) expression. Cases exposed to high dose letrozole 10 mg day -1 resulted in a higher ectopic pregnancy resolution rate of 85% (17/20), while the resolution rate of the low dose letrozole-treated group (5 mg day -1 ) was 65% (13/20), and also showed a significant reduction in β-hCG levels on the 11th day, 25.63 ± 4.29 compared to the low dose letrozole group 37.91 ± 7.18 (P < 0.001), Meanwhile, the letrozole-treated group GIV showed markedly reduced expression of ER, PR, and VEGF and a significant increase in the apoptotic index cleaved caspase-3 compared to the control group (P < 0.001). The utilization of letrozole at a dose of 10 mg day -1 for medical treatment of ectopic pregnancy results in a high-successful rate without any severe side effects. Letrozole depriving the placenta of estrogen that had vascular supporting signals resulted in destroying the vascular network with marked apoptosis., (© 2022. The Author(s).)

Epilepsy is a prevalent and chronic neurological disorder marked by recurring, uncontrollable seizures of the brain. Chronic or repeated seizures produce memory problems and induce damage to different brain regions. Histamine has been reported to have neuroprotective effects. Betahistine is a histamine analogue. The current research investigated the effects of convulsions on the cerebral cortex and hippocampus of adult male albino mice and assessed the possible protective effect of betahistine. Four groups of 40 adult male mice were organized: control, betahistine (10 mg/kg/day), pentylenetetrazole (PTZ) (40 mg/kg/ on alternate days), and Betahistine-PTZ group received betahistine 1 h before PTZ. PTZ induced a substantial rise in glutamate level and a considerable decrease in histamine level. Structural changes in the cerebral cortex and cornu ammonis (CA1) of the hippocampus were detected in the pattern of neuron degeneration. Some neurons were shrunken with dark nuclei, and others had faintly stained ones. Focal accumulation of neuroglial cells and ballooned nerve cells of the cerebral cortex were also detected. Cleaved caspase-3, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule 1 showed substantial increases, while synaptophysin expression was significantly reduced. Interestingly, these changes were less prominent in mice pretreated with betahistine. In conclusion, betahistine had shown neuroprotective properties against brain damage induced by convulsions.

Imidacloprid (IMID), one of environmental persistent neonicotinoid insecticides, has been used a long time ago and categorized from insecticide induced moderate toxicity by World Health Organization (WHO). Marjoram, is one of the most worldwide used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, anti-mutagenic, anticoagulant, and beneficial effects. This study aimed to evaluate the protective role of marjoram extract on the immunotoxic response and oxidative stress induced by IMID in the immune lymphoid organs (thymus and spleen) of rats. Fifty adult male albino rats were divided randomly into five groups; negative and positive (distilled water) control, marjoram extract (200 mg/kg/day), IMID (22.5 mg/kg/day), marjoram extract + IMID (200 mg/kg +22.5 mg/kg) orally for 8 weeks. Marjoram pretreatment reversed reduced animals body, thymus and spleen weights attributed to IMID. It amended the significantly elevated total leukocytes, neutrophils percentage, increased immunoglobulin G and the significantly reduction of lymphocytes percentage, phagocytic activity, phagocytic index and lysozyme activity induced by IMID. Moreover, marjoram administration significantly reduced thymic and splenic gene expression of interleukin-1β, interleukin-6, tumor necrosis factor-α and increased interleukin-10, in addition, it decreased thymic and splenic contents of malondialdehyde and restored the reduced antioxidant enzymes' activities following IMID exposure. Marjoram ameliorated IMID induced histopathological alterations in thymus and spleen and adjusted IMID immunomodulatory effects by increased the downregulation of CD4 and CD8 immune reactive cell expression. Conclusion, Marjoram has a protective role to reverse IMID immune toxic effects in thymus and spleen tissues of rats by its antioxidant, anti-inflammatory and immunomodulatory defense mechanisms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vincristine is a chemotherapy drug that belongs to the vinca alkaloids group. It is used for treatment of hematologic malignancies and several solid tumors. Vincristine-induced peripheral neuropathy is a major dose-limiting side effect. Coenzyme Q10 (Co Q10), an essential component of the mitochondrial electron transport chain, participates in energy production. It is a powerful fat-soluble antioxidant and also exerts anti-inflammatory effects. Therefore, this study was aimed to focus on the mechanistic insights of vincristine-induced peripheral neuropathy in addition to shedding the light on the modulatory effect of Co Q10. Twenty-eight rats were randomly divided into four groups. Peripheral neuropathy was induced by intraperitoneal injection of vincristine (0.1 mg/kg body weight). Co Q10 was injected intraperitoneally (10 mg/kg body weight) for 24 days. Sciatic nerve MDA, TAC, GSH, 8-OHdG, TNF-α, IL-1β, and NF-κB levels were assessed. Gene expression of SARM1 and Nrf2 was also assessed. Serum neurofilament light chain was immunoassayed, in addition to the behavioral assessment. Co Q10 significantly improved oxidative stress and inflammatory biomarkers. It also decreased serum NFL levels. It enhanced Nrf2 and decreased SARM1 gene expression. Histopathological findings proved the biochemical and molecular findings. Our results support Co Q10 as a potential protective agent against vincristine-induced peripheral neuropathy., (© 2021 Wiley Periodicals LLC.)

A human is exposed to a chemical mixture rather than a single chemical, particularly with the wide spread of nanomaterials. Therefore, the present study evaluated the combined exposure of lead acetate (Pb) and zinc oxide-nanoparticles (ZnO-NPs) compared to each metal alone on the thyroid gland of adult rats. A total of 30 adult male albino rats were divided into four groups, group I (control), group II received Pb (10 mg/kg), group III received ZnO-NPs (85 mg/kg) and group IV co-administrated the two metals in the same previous doses. The materials were gavaged for 8 weeks. The toxicity was assessed through several biochemical parameters. Our results revealed significant body weight reduction relative to increased thyroid weights, decreased both of serum-free triiodothyronine (FT3), tetra-iodothyronine (FT4), increased thyroid-stimulating hormone (TSH), increased serum and thyroid levels of Pb and zinc, significant elevation in tumor necrosis factor-α (TNF-α), reduction in interleukin 4 (IL4), upregulation of Bax, and downregulation of Bcl-2 genes. Additionally, there was significant overexpression of nuclear factor erythroid 2-related factor 2(Nrf2), 8-Hydroxydeoxyguanosine(8-OHdG), the elevation of tissues malondialdehyde (MDA), reduction of tissues total antioxidant capacity (TAC), and disruptive thyroid structural alterations in all metals groups with marked changes in the combined metals group. In conclusion, the combined exposure of Pb and ZnO-NPs induced pronounced toxic thyroid injury, pointing to additive effects in rats than the individual metal effects through different significant changes of disruptive thyroid structural alterations related to the loading of thyroid tissues with Pb and zinc metals producing oxidative stress that mediated inflammation and apoptosis., (© 2021 Wiley Periodicals LLC.)

Metanil yellow is a food dye that has harmful impacts on different body systems. Scutellarin has antioxidant, antiapoptotic, and anti-inflammatory activities. The aim of the current research was to study the effect of chronic administration of metanil yellow on the cerebellar cortex of rats and to evaluate the protective effect of scutellarin. Forty adult male rats were allocated into four groups: group I acted as control, group II was administrated scutellarin (100 mg/kg/day), group III was administrated metanil yellow (200 mg/kg/day), and group IV was administrated scutellarin and metanil yellow as in group II and group III. The agents were administered via oral gavage for 8 weeks. Metanil yellow induced a significant rise in the malondialdehyde coupled with a significant reduction in the superoxide dismutase and glutathione peroxidase. The Purkinje cells were irregular and shrunken with condensed nuclei. A significant elevation in glial fibrillary acidic protein (GFAP) and cleaved caspase-3 as well as a significant reduction of synaptophysin expression were revealed in comparison with the control group. Interestingly, few changes were noticed in rats given metanil yellow concomitant with scutellarin. In conclusion, scutellarin could protect against metanil yellow-induced alterations in the cerebellar cortex by reducing oxidative stress and minimizing gliosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues., Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients., Patients and Methods: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60)., Results: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001). In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function., Aim: This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival., Conclusion: PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Currently, the golden rule for the diagnosis of urothelial carcinoma is biopsy and cystoscopy, unfortionally both are costly, invasive, and uncomfortable. While most urothelial cancers are noninvasive at presentation, it is necessary to find a highly sensitive, noninvasive way to diagnose in its earlier stages, Cytology with immunostaining is a noninvasive, reliable method that might play a role in detecting the earlier stages before its progression and accurate correlation with different stages of these tumors., Aim: This study aimed to reach an accurate level in the staging of urothelial carcinoma using CD44, ProExC, Laminin, and Fascin on urinary cytology., Design: We include a total of 180 urinary cytology specimens with their surgical biopsies' counterparts, the staging of the surgical specimens were done according to AJCC2017TNM classification, while their counterpart urinary samples were centrifuged and the sediment was used for H&E and immunocytochemical staining with CD44, ProExC, Laminin, and Fascin., Results: The diagnosis of Ta-stage tumors was done according to the following immunohistochemical (IHC) profile [positive (+ve) CD44, negative (-ve) proExC, -ve Laminin, and -ve Fascin] with 100% sensitivity, 100% specificity. The diagnosis of Tis stage tumors was done according to IHC profile [-ve CD44, +ve proExC, -ve Laminin, and -ve Fascin] with 100% sensitivity, 93% specificity. The diagnosis of T1 stage tumors according to IHC profile [-ve CD44, +ve proExC, +ve Laminin, and -ve Fascin] with 100% sensitivity, 97% specificity, The diagnosis of T2 and T3 stage tumors was done according to IHC profile [-ve CD44, +ve proExC, +ve Laminin and weak to moderate +ve Fascin] with 100% sensitivity, 92% specificity, while the diagnosis of T4 stage tumors according to the IHC profile [-ve CD44, +ve proExC, +ve Laminin, and intense +ve Fascin] with 100% sensitivity, 100% specificity., Conclusion: Using (CD44, ProExC, Laminin, and Fascin) on urinary cytology is a simple, reliable, and noninvasive method for the staging of urothelial carcinoma with 99% total accuracy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Diabetes mellitus (DM) represents a widespread metabolic disease with a well-known neurotoxicity in both central and peripheral nervous systems. Oxymatrine is a traditional Chinese herbal medicine that has various pharmacological activities including: anti-oxidant, anti-apoptotic and anti-inflammatory potentials. The present work aimed t o study the impact of diabetes mellitus on the cerebellar cortex of adult male albino rat and to evaluate the potential protective role of oxymatrine. Fifty-five adult male rats were randomly divided into three groups: group I served as control, group II was given oxymatrine (80 mg/kg/day) orally for 8 weeks and group III was given a single dose of streptozotocin (50 mg/kg) intaperitoneally to induce diabetes. Then diabetic rats were subdivided into two subgroups: subgroup IIIa that received no additional treatment and subgroup IIIb that received oxymatrine similar to group II. The diabetic group revealed numerous changes in the Purkinje cell layer in the form of multilayer arrangement of Purkinje cells, shrunken cells with deeply stained nuclei as well as focal loss of the Purkinje cells. A significant increment in glial fibrillary acidic protein (GFAP) and synaptophysin expression were reported in immunohistochemistry compared with the control group. Transmission electron microscopy showed irregularity and splitting of myelin sheaths in the molecular layer, dark shrunken Purkinje cells with ill-defined nuclei, dilated Golgi saccules and dense granule cells with irregular nuclear outlines in the granular layer. In contrast, these changes were less evident in diabetic rats that received oxymatrine. In conclusion, Oxymatrine could protect the cerebellar cortex against changes induced by DM.

Background & Objective: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry., Methods: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values., Results: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC ( P < 0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression ( P =0.038 and P =0.019, respectively)., Conclusion: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Recurrent spontaneous abortion is an obstetric complication with undefined causes. Apoptosis, proliferation, and adhesion are considered important factors in the pathogenesis of abortion. This work aimed to determine Bax and Bcl-2 as a proapoptotic and antiapoptotic protein, Ki67 and P27kip as proliferative and antiproliferative proteins, and E-cadherin and CD44 as adhesion molecules in the trophoblastic tissues in cases with recurrent miscarriage. Immunohistochemistry and quantitative polymerase chain reaction analysis of Bax, Bcl-2, Ki67, P27kip, E-cadherin, and CD44 in paraffin-embedded sections of placental tissues obtained from 108 women were divided into 3 categories: 66 Toxoplasma gondii-positive women with recurrent abortion, 22 T. gondii-negative women with recurrent abortion, and 20 women with no history of abortion as a control group. The mean ratio of the expression of Bax and P27kip proteins was 35.3% and 36.1%, which is significantly higher than that of the second group (19.88 and 20.02%), and the third group (12.3% and 10.98%), while the mean ratio of the expression of Bcl-2, Ki67, E-cadherin, and CD44 proteins was 12.35%, 11.23%, 10.32%, and 9.97%, which is significantly lower than that of the second group (33.75%, 13.18%, 21.88%, and 23.29%) and that of the third group (38.58%, 39.27%, 37.98%, and 35.79%). The presence of proapoptotic protein (Bax) and antiproliferative protein (P27kip) at high levels and the presence of antiapoptotic protein (Bcl-2), proliferative protein (Ki67), and adhesion molecules (E-cadherin and CD44) in lower levels in the T. gondii-positive group clarify the mechanism involved in the induction of abortion and loss of pregnancy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Finasteride is commonly used in the management of alopecia and nodular prostatic hyperplasia. It was reported to have a harmful effect on spermatogenesis with subsequent infertility. Thus, this research was to determine the ameliorative effect of resveratrol against testicular damage caused by finasteride. Forty adult male rats were randomly divided into four main groups: group I acted as the control, group II was administrated resveratrol 20 mg/kg/day, group III was administrated finasteride 5 mg/kg/day, and group IV was administrated finasteride and resveratrol as in the previous groups. Finasteride induced a significant decrement in the testosterone and dihydrotestosterone levels. The level of malondialdehyde significantly increased, while the levels of glutathione peroxidase, superoxide dismutase, and catalase significantly decreased in the finasteride-administrated rats. Variable histopathological alterations in the testes were revealed in the form of irregular seminiferous tubules. Some seminiferous tubules appeared with degenerated germinal epithelium. Others showed detachment of their germinal epithelium. Congested blood vessels and homogeneous acidophilic substance in-between tubules were also detected. A significant decrement in PCNA positive cells and a significant increment in Bax expression were demonstrated. Ultrastructural examination showed Sertoli cells with rarefied cytoplasm. Vacuolated cytoplasm, shrunken nuclei, and dilated perinuclear spaces were also revealed in the spermatogonia, primary spermatocytes, and early spermatids. On the contrary, few changes were noticed in rats received resveratrol concomitant with finasteride. This study indicated that resveratrol exerted a potent ameliorative effect against testicular injury caused by finasteride.

Tramadol is a centrally acting analgesic drug, used for the management of moderate to severe pain in a variety of diseases. The long-term use of tramadol can induce endocrinopathy. This study aimed to evaluate the effect of tramadol dependence on the adrenal cortex and the effect of its withdrawal. Thirty adult male rats were divided into three experimental groups: the control group, the tramadol-dependent group that received increasing therapeutic doses of tramadol orally for 1 month, and the recovery group that received tramadol in a dose and duration similar to the previous group followed by a withdrawal period for another month. Specimens from the adrenal cortex were processed for histological, immunohistochemical, enzyme assay, and quantitative real-time PCR (RT-qPCR) studies. Tramadol induced a significant increase in malondialdehyde level and a significant decrease in the levels of glutathione peroxidase and superoxide dismutase. A significant decrease in the levels of adrenocorticotrophic hormones, aldosterone, cortisol, corticosterone, and dehydroepiandrosterone sulfate was also detected. Severe histopathological changes in the adrenal cortex were demonstrated in the form of disturbed architecture, swollen cells, and shrunken cells with pyknotic nuclei. Inflammatory cellular infiltration and variable-sized homogenized areas were also detected. A significant increase in P53 and Bax immunoreaction was detected and confirmed by RT-qPCR. The ultrastructural examination showed irregular, shrunken adrenocorticocytes with dense nuclei. Dilated smooth endoplasmic reticulum, mitochondria with disrupted cristae, and numerous coalesced lipid droplets were also demonstrated. All these changes started to return to normal after the withdrawal of tramadol. Thus, it was confirmed that the long-term use of tramadol can induce severe adrenal changes with subsequent insufficiency.

The initiation of prostatic malignancy has been linked to chronic inflammation. Stem cell factor (SCF) is an inflammatory cytokine that is specific to the c-KIT receptor which is type III receptor tyrosine kinase (RTK). Cyclooxygenases (COXs) are the main enzymes which are responsible for prostaglandins production from arachidonic acid. COX2 is an enzyme which is produced under different pathological conditions. The aim of our study; is to investigate the clinicopathological and the prognostic significance of SCF and COX-2 expression in prostatic adenocarcinoma (PC), chronic prostatitis and nodular prostatic hyperplasia (NPH) in a trial to clarify the role of inflammation as a risk factor for prostatic carcinogenesis and cancer progression. SCF and COX-2 tissue protein expression were evaluated in 50 cases of PC, 20 cases of chronic prostatitis and 10 cases of NPH using immunohistochemistry, patients were followed up for 5 years. The relationship between their levels of expressions, clinicopathological, and prognostic criteria were studied. SCF expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.010), higher Gleason score (p = 0.011). COX-2 expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.016), advanced D'Amico risk group (p = 0.038). High levels of expression of both SCF& COX-2 are associated with higher incidence of tumor relapse, worse disease overall survival and free survival (p < 0.001). SCF and COX-2 are associated with PC progression and associated with poor prognosis in PC patients.