Erdheim-Chester Disease Presenting as Bilateral Facial Masses: A case report and review of literature.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with unknown aetiology. It is recently recognised to be neoplastic with genetic mutations affecting the mitogen-activating protein kinase pathway. We report a 49-year-old female patient who initially presented in 2012 to a tertiary care centre in Muscat, Oman, with bilateral facial masses. These were removed but later recurred over a period of 10 years. She then presented with xanthelasmas, bone lesions, secondary infertility due to hypothalamic hypogonadism, diabetes insipidus and Hashimoto's hypothyroidism. The facial masses were biopsied and they showed classic morphological features in the form of diffuse infiltration by foamy histiocytes with scattered Touton type of giant cells, patchy lymphocytic infiltrates and dense fibrosis. The patient is stable and is being followed-up. The presented ECD case is particularly interesting due to the recurrent bilateral facial masses. To the best of the authors' knowledge, this is the first documented case in Oman.

A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer.

The rising incidence and mortality of early-onset colorectal cancer (EOCRC) emphasize the urgent need for effective non-invasive screening. Circulating microRNAs (miRNAs) have emerged as promising biomarkers for cancer detection. This systematic review aims to evaluate the diagnostic performance of circulating miRNAs in detecting colorectal cancer (CRC). A literature search was conducted in PubMed and Scopus. Studies that report sensitivity, specificity, or area under the curve (AUC) for CRC detection by miRNA were included. The miRNA miR-21 was the most frequently studied biomarker, with a varying range of AUC from 0.55 to 0.973 attributed to differences in study populations and methodologies. The miRNAs miR-210 and miR-1246 showed potential diagnostic capacity with miR-1246 achieving an AUC of 0.924, 100% sensitivity, and 80% specificity. The miRNA panels offer improved diagnostic performance compared to individual miRNA. The best performing panel for CRC patients below 50 is miR-211 + miR-25 + TGF-ß1 with AUC 0.99 and 100 specificity and 97 sensitivity. Circulating miRNAs hold significant promise as non-invasive biomarkers for CRC screening. However, the variability in diagnostic performance highlights the need for a standardized method and robust validation studies. Future research should focus on large-scale, ethnically diverse cohorts to establish clinically relevant miRNA biomarkers for CRC, particularly in younger populations.

Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors.

BACKGROUND: Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR. METHODS: A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers. RESULTS: Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters. CONCLUSIONS: This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

Factors affect knowledge, attitudes, and practices in colorectal cancer screening: A systematic review.

OBJECTIVES: This review aimed to synthesize the available evidence on exploring various factors that affect knowledge, attitudes, and practices (KAP) in colorectal cancer (CRC) screening. METHODS: A systematic search across five databases was performed to identify factors influencing KAP scores towards CRC screening. The PRISMA guidelines were used to conduct the literature search, and the time spanned is from March to June 2023. The search included observational studies published between January 2000 and June 2023 that met the predetermined review criteria. Data were extracted following the Joanna Briggs Institute (JBI) appraisal checklist to evaluate the quality of the articles. RESULTS: Out of 16,904 records, 1174 articles were reviewed in full text, resulting in 43 high-quality studies included based on the JBI checklist. These studies assessed knowledge (42), attitudes (26), and practices (11) related to CRC screening. Key factors to improving KAP towards CRC screening in the general public were sociodemographic, social media influence, and physician recommendations. For healthcare professionals, factors promoting KAP included screening methods, guidelines, qualifications, and understanding of CRC screening. Educators lacked awareness of CRC symptoms and needed training to teach CRC screening and prevention. Pharmacists showed positive attitudes towards early CRC detection but had varying knowledge levels. CONCLUSIONS: KAP towards CRC screening is suboptimal among the general public, healthcare professionals, students, educators, and pharmacists worldwide. Routine CRC screening counselling is paramount to improving screening rates. Continuous medical education and training programmes are essential for healthcare professionals to enhance their KAP towards CRC screening. Students and university teachers should be educated and trained about CRC screening to improve their knowledge and foster positive behavioural changes. These comprehensive measures are critical for establishing an effective screening programme.

Analysis of Immunohistochemical Expression of BRAF (V600E) Mutation in Serrated Colorectal Polyps: A Study from Tertiary Hospital in Oman.

BACKGROUND AND AIM: Colorectal cancer (CRC) is considered one of the most common cancers in the world. Serrated polyps were found to be precursor lesions for CRC. BRAF mutation (V600E) has been strongly linked to the development of these lesions. No previous study concerning BRAF immunohistochemical expression in serrated polyps- was done in Oman. The primary objective of our study was to assess the prevalence of BRAF (V600E) mutation in serrated colorectal polyps in the Omani population. The secondary objectives were to assess the prevalence of serrated polyps and their characteristic features: type, site and size as well as the relationship between BRAF (V600E) mutation and polyp type, site and size. MATERIALS AND METHODS: Ninety-one hyperplastic polyps (HP) (76.5%), 24 sessile serrated lesions (SSL) (20.2%) and 4 cases of tubular adenomas with low grade dysplasia (3.4%) were studied for BRAF (V600E) immunohistochemical expression. No case of traditional serrated adenoma (TSA) was present. Control cases of craniopharyngioma and papillary thyroid carcinoma were included. RESULTS: BRAF (V600E) IHC was positive in 63 of the HP polyps (69.2%), 13 SSLs (54.2%) and none of the adenomatous polyps. The majority of positive polyps (75.0%) were ≤5 mm in size, 17.9% were 5-10 mm and 7.1% were ≥10 mm in size.  The majority of BRAF (V600E) positive polyps (68.1 %) were in the distal colon and 31.9 % were in the proximal colon. The majority of positive cases for BRAF (V600E) were showing multiple polyps (61.8 %). None of the tubular adenomas showed any BRAF (V600E) positivity. CONCLUSION: Serrated polyps are now well known for their potential to develop CRC. Immunohistochemistry is an easy and reproducible way to detect BRAF (V600E) mutation. Our study showed there is high prevalence (64.3%) of BRAF mutation in serrated polyps in the Omani population. The majority of these polyps- were HP and SSL; and ≤5 mm in size and located in the distal colon.

Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.

The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters. METHODS: Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically. RESULTS: The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse).  There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively). CONCLUSION: EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.

Avastin-Loaded 3D-Printed Alginate Scaffold as an Effective Antiadhesive Barrier to Prevent Postsurgical Adhesion Bands Formation.

Postoperative adhesion can cause complications, such as pain and organ blockage, in the abdominal regions. To address this issue, surgical techniques and antiadhesive treatments are applied. Given the significant role of vascularization in adhesion band formation, Avastin (Ava) that targets vascular endothelial growth factor (VEGF) can be applied to prevent peritoneal adhesion bands. Moreover, Alginate (Alg), a natural polysaccharide, is a promising physical barrier to prevent adhesion bands. Incorporating Ava into Alg hydrogel in a form of 3D-printed scaffold (Alg/Ava) has potential to suppress inflammation and angiogenesis, leading to reduce peritoneal adhesion bands. Following physical, morphological, and biocompatibility evaluations, the efficacy of Alg and Ava alone and their combination in Alg/Ava on the formation of postsurgical adhesions is evaluated. Upon confirming physical stability and sustained release of Ava, the Alg/Ava scaffold effectively diminishes both the extent and strength of adhesion bands. Histopathological examination shows that the reduction in fibrosis and inflammation is responsible for preventing adhesion bands by the Alg/Ava scaffold. Additionally, the cytokine assessment reveals that this is due to the inhibition in the secretion of VEGF and Interleukin 6 suppressing vascularization and inflammatory pathways. This study suggests that a 3D-printed Alg/Ava scaffold has great potential to prevent the postsurgical adhesion bands.

NADH intraperitoneal injection prevents massive pancreatic beta cell destruction in a streptozotocin-induced diabetes in rats.

Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia, revealing a decrease in insulin efficiency. The sustained glucotoxic pancreatic microenvironment increases reactive oxygen species generation, resulting in chronic oxidative stress responsible for massive DNA damage. This triggers PARP-1 activation with both NAD+ and ATP depletion, affecting drastically pancreatic beta cells' energy storage and leading to their dysfunction and death. The aim of the present study is to highlight the main histological changes observed in pancreatic islets pre-treated with a unique NADH intraperitoneal injection in a streptozotocin-(STZ)-induced diabetes model. In order to adjust NADH doses, a preliminary study with three different doses, 500 mg/kg, 300 mg/kg, and 150 mg/kg, respectively, was conducted. Subsequently, and on the basis of the results of the aforementioned study, Wistar rats were randomly divided into four groups: non-diabetic control group, diabetics (STZ 45 mg/kg), NADH-treated group (150 mg/kg) 15 min before STZ administration, and NADH-treated group (150 mg/kg) 15 min after STZ administration. The effect of NADH was assessed by blood glucose level, TUNEL staining, histo-morphological analysis, and immunohistochemistry. The optimum protective dose of NADH was 150 mg/kg. NADH effectively decreased hyperglycemia and reduced diabetes induced by STZ. Histologically, NADH pre-treatment revealed a decrease in beta cell death favoring apoptosis over necrosis and therefore preventing inflammation with further beta cell destruction. Our data clearly demonstrate that NADH prior or post-treatment could effectively prevent the deleterious loss of beta cell mass in STZ-induced diabetes in rats and preserve the normal pancreatic islet's function.

Malignant Gastrointestinal Neuroectodermal Tumor of Small Intestine Showing DOG1 Expression: A Case Report and Review of Literature.

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like tumor of the GI tract is a rare mesenchymal tumor of the gastrointestinal tract. It has to be distinguished from various mimickers including gastrointestinal stromal tumor (GIST) due to its aggressive course and different natural history and therapeutic approach. Here we report a case of GNET arising in the small intestine with aberrant DOG1 expression posing a diagnostic challenge. In this context, the combination of clinical, histomorphological, immunohistochemical, and molecular features helped to establish a proper diagnosis.

Alveolar Soft Part Sarcoma of the Tongue: A Rare Tumor at an Unusual Location.

Alveolar soft part sarcoma (ASPS) is a rare type of soft tissue sarcoma that typically affects adolescents and young adults, though it can occur at any age. We report a case of ASPS of the tongue, which is extremely rare at this location. The patient presented with a polypoidal lesion on the tongue, a biopsy of which showed granular and alveolar morphology. A definitive diagnosis was not rendered due to limited tissue. The case was discussed with the treating surgeon, and excision was recommended with clear margins. Excision of the lesion showed typical ASPS. A TFE-3 immunohistochemical stain was done, which showed strong immunoreactivity, thereby confirming the diagnosis of ASPS. This tumour is rare, and its presence in the tongue makes it extremely infrequent.

Correlation of PD-L1 immunohistochemical expression with microsatellite instability and p53 status in endometrial carcinoma.

Background: Endometrial carcinoma (EC) is the most common gynaecological cancer worldwide. The Cancer Genome Atlas molecular grouping of a given case of EC could be assessed by POLE gene mutation, mismatch repair (MMR) 'to reflect microsatellite instability' and p53 status, which has proved to be of prognostic value. Programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) are playing a progressively important role in tumour immunology and cancer treatment. Objectives: To investigate PD-L1 immunohistochemical expression in EC in relation to MMR and p53 status. Associations between marker expression and different histopathological parameters were also investigated. Methods: This retrospective study was performed on archival biopsies of 170 cases of EC using a tissue microarray model. Immunohistochemical staining was applied using antibodies against PD-L1, MLH1, MSH2 and p53. Results: The percentages of positivity were as follows: PD-L1, 19.6%; MLH1, 79.5%; MSH2, 78.5%; and p53 mutant, 13.8%. There was significant correlation between MLH1 expression and MSH2 expression (p = 0.008). Tumour grade was significantly correlated with stage (p = 0.005) and p53 mutant expression (p = 0.008). Combined PD-L1 positivity and MMR deficiency showed significant correlation with the presence of lymphovascular space invasion (p = 0.014). MSH2 negativity was significantly associated with poorer overall survival (p = 0.014). Conclusions: A panel of immunohistochemical markers (PD-L1, MLH1, MSH2 and p53) could help to predict the prognosis and plan the treatment of patients with EC. MMR deficiency seems to be a good predictor for PD-L1 status, and therefore the response to potential PD-1/PD-L1 inhibitor therapy.

Prevention of post-surgical adhesion bands by local administration of frankincense n-hexane extract.

Background: and purpose: The formation of postoperative intra-abdominal adhesion band formation may lead to severe complications. This study aimed to evaluate the preventive effect of local administration of frankincense n-hexane extract (FHE) on the formation of postsurgical adhesion bands. Materials and methods: FHE was extracted from the resin of a Boswellia sacra tree and its components were identified by gas chromatography-mass spectrometry (GC-MS). In an animal model, the expression levels of TNF-α and TGF-ß1 cytokines after application of FHE were assessed to check the inflammatory and fibrotic cues, respectively. Results: Following FHE compound analysis, in vivo experiments demonstrated that intraoperative local administration of FHE resulted in the prevention of adhesion band formation. The adhesion grades in the FHE-treated group were significantly lower than those in the negative control (NC) and the positive control (Interceed). The infiltration of inflammatory cells observed by histopathology revealed a significant anti-inflammatory potential of FHE. Furthermore, the gene expression results proved that significant suppression of TNF-α and TGF-ß1 was responsible for its antiadhesion properties. Conclusions: The study reported the potential of FHE as an ointment for the prevention of adhesion bands.

Correlation of expression of Akt1 and E2F1 and their phosphorylated forms in breast cancer patients with clinicopathological parameters.

Breast cancer is the leading cancer worldwide among women. Traditional clinicopathological prognostic and predictive markers need refining to improve clinical outcomes. This study explored the association between traditional clinicopathological factors and the expression of Akt1 and E2F1 transduction proteins and their phosphorylated forms in breast cancer, to determine their value as novel biomarkers and potential therapeutic targets. Tumor tissues from 94 female breast cancer patients were examined for immunophenotypic expression of total Akt1, pAkt1 (Serine 473), pAkt1 (Threonine 308), total E2F1, pE2F1 (Thr433) and pE2F1 (Ser337). The expression of pAkt1 (Ser473) was significantly associated with ER/PR positive status and total E2F1 with older age (> 50), lymph node involvement and HER2 positivity. There was a significant association between triple negative cancers and total and pAkt1 (Thr308). pAkt1 (Ser473) showed an inverse relationship with Luminal B cancers and pE2F1 (Thr433) showed an inverse association with triple negative cancers. Higher expression of pE2F1 (Ser337) was associated with better OS. Both pAkt1 (Ser473 and Thr308) proteins showed significant association with poorer patient outcomes. E2F1 (Ser337) showed a significant positive correlation with response to chemotherapy. The study suggests that a pAkt1-/pE2F1+ phenotype could indicate an opportunity to minimize chemotherapeutic options in older women; conversely a pAkt1+/pE2F1- phenotype could prompt a more aggressive regimen. Further exploration of this phenotype in younger women with breast cancer and triple-negative breast cancers is warranted.

A competitive nature-derived multilayered scaffold based on chitosan and alginate, for full-thickness wound healing.

The aim of this study was to evaluate a bioactive multilayer wound dressing, based on chitosan and alginate. To enhance healing potential, Dracaena Cinnabari and Aloe Vera were loaded as separate layers into the scaffold. The bare and bioactive multilayered scaffolds were fabricated by an iterative layering freeze-drying technique. Following of topographical, chemical, and physical assessment, the performance of the scaffolds was evaluated in vitro and in vivo. The results revealed adequate attachment, and proliferation of human foreskin fibroblasts, indicating excellent biocompatibility of the bioactive scaffold. In vivo, the performance of the multi-layered scaffold loaded with the bioactive materials was comparable with Comfeel plus®. The wounds treated with the bioactive scaffold exhibited superior hypergranulation, fibroblast maturation, epithelization, and collagen deposition, with minimal inflammation, and crust formation. It is concluded that the synergism of extracellular matrix-mimicking multi-layered scaffolding with Aloe Vera and Dracaena Cinnabari could be considered as a supportive wound dressing.

Effect of tocilizumab, an interleukin-6 inhibitor, on early stage streptozotocin-induced diabetic nephropathy in rats.

The aim of this study was to examine the effect of tocilizumab, an interleukin-6 (IL-6) inhibitor on streptozotocin-induced diabetic nephropathy. Male Sprague-Dawley rats (n = 36) were distributed into six groups and treated for 4 weeks. Groups 1, 3, 5 received either saline, tocilizumab (2 mg/kg), or tocilizumab (8 mg/kg) injection intraperitoneally (i.p.), every 2 weeks, respectively. Groups 2, 4, 6 were rendered diabetic by a single i.p. injection of streptozotocin (65 mg/kg) and were treated as in groups 1, 3, 5, respectively. Biochemical parameters were measured in plasma, urine, and kidneys. In the untreated diabetic group, there was a significant decrease in body weight, polyuria, and increased kidney weight. There was increased urinary albumin/creatinine ratio (UACR) and N-acetyl-ß-D-glucosaminidase (NAG)/creatinine ratio (UNCR). Streptozotocin also induced a significant increase in creatinine clearance. In addition, diabetes was associated with increased oxidative stress [reduced renal glutathione reductase (GR), superoxide dismutase (SOD), catalase activities, and increased malondialdhyde (MDA)] and increased plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) concentrations. Kidneys from streptozotocin-treated rats showed marked vacuolation of the proximal tubular epithelium with focal tubular necrosis and the glomeruli showing increase in mesangial cells. Tocilizumab significantly mitigated the increase in UACR and UNCR, renal MDA, plasma TNF-α, IL-6 and NO levels, and the decrease in renal SOD and catalase activities in diabetic rats. Tocilizumab did not significantly improve creatinine clearance; however, it attenuated the histopathological changes induced by streptozotocin. This study shows that tocilizumab was able to ameliorate some of the changes seen in streptozotocin-induced early diabetic nephropathy in rats. This is mainly due to its anti-inflammatory and antioxidative effects.

Effect of levosimendan, a calcium sensitizer, on cisplatin-induced nephrotoxicity in rats.

We investigated the effect of levosimendan on cisplatin (Cis)-induced nephrotoxicity. Rats were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (6 mg/kg) on day 7, respectively. The third and fourth groups received a single intraperitoneal (i.p.) injection of Cis on day 7 and levosimendan (1 mg/kg/day, orally) or vehicle for 10 days, respectively. At day 11, animals were anaesthetized and blood collected and kidneys removed. Another four groups were treated the same as the previous four groups to measure renal blood flow. Cis induced nephrotoxicity as evidenced by biochemical, histopathological and hemodynamic changes. Levosimendan partially reduced Cis-induced increase in plasma urea, creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels and decrease in creatinine clearance. Levosimendan partially reduced Cis-induced increase in urinary albumin/creatinine ratio, N-Acetyl-ß-D-Glucosaminidase (NAG) and kidney Injury Molecule-1 (KIM-1). Levosimendan significantly attenuated the effect of Cis on plasma concentration of plasma tumor necrosis factor-alpha (TNF-α), antioxidant indices [catalase and superoxide dismutase (SOD)] and lipid peroxidation. Cis induced acute tubular necrosis with tubular dilatation, interstitial edema and congestion. Levosimendan attenuated the remarkable renal damage and reduced renal blood flow induced by Cis. In conclusion this study shows that levosimendan has a partial protective effect on Cis-induced nephrotoxicity. The protective effect of levosimendan is shown to be related to its anti-inflammatory, antioxidant and vasodilator effects.

The Value of Programmed Death Ligand 1 Expression in Cancer Patients Treated with Neoadjuvant Chemotherapy.

Programmed death ligand 1 (PD-L1) is an inhibitory molecule expressed by cancer cells to supress T-cell activity and escape anti-tumour immunity. The role of PD-L1 in cancer has been studied extensively as it is considered an important immune checkpoint against immune over-activation through its interaction with Programmed death receptor 1 (PD-1) expressed on activated lymphocytes. PD-L1 expression was found to be enhanced by chemotherapy through different proliferation pathways. However, the predictive and prognostic value for PD-L1 expression in cancer patients treated with neoadjuvant chemotherapy (NAC) is not yet established. This review focused on the potential effects of chemotherapy on PD-L1 expression and the role of PD-L1 as a prognostic and predictive marker in NAC-treated cancer patients. In addition, the potential use of this marker in clinical practice is discussed.

Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on cisplatin-induced nephrotoxicity in mice.

Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that is currently available for the management of type 2 diabetes mellitus. The present study investigated the effect of canagliflozin on cisplatin (CP)-induced nephrotoxicity in mice. The animals were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (20 mg/kg) on day 7, respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (20 mg/kg) on day 7 and canagliflozin (10 mg/kg/day) and (30 mg/kg/day), for 10 days, respectively. At day 11, animals were anesthetized and blood collected and kidneys were removed. CP significantly increased the plasma urea, creatinine, cystatin C, and clusterin concentrations and neutrophil gelatinase-associated lipocalin (NGAL) activity. In addition, CP increased urinary albumin/creatinine ratio, N-acetyl-ß-D-glucosaminidase (NAG) activity, and liver-type fatty acid-binding protein (L-FABP) concentrations and reduced creatinine clearance. CP also significantly increased the plasma concentration of inflammatory cytokines [plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß)] and significantly reduced antioxidant indices [catalase, glutathione reductase (GR), and superoxide dismutase (SOD)]. Histopathologically, CP caused a remarkable renal damage compared with control. Canagliflozin significantly ameliorated CP-induced biochemical and histopathological changes. The protective effect of canagliflozin is most likely due to anti-inflammatory and antioxidant effects. Our results show that administration of canagliflozin reversed the biochemical and histopathological indices of CP-induced nephrotoxicity in mice.

Evaluation of the role of Notch1 expression in hepatic carcinogenesis with clinico-pathological correlation.

The role of Notch pathway in hepatocarcinogenesis is unclear with conflicting results reported from different researchers. This study aimed to investigate the exact role of Notch1 in hepatocarcinogenesis and its influence on survival and to determine the possibility of it being a target therapy. Differential immunohistochemical expression of Notch1 in 100 cases of hepatocellular carcinoma (HCC) and adjacent non-neoplastic liver tissue was performed. The results showed that expression of Notch1 was significantly higher in the non-neoplastic hepatic tissues than in HCC tissues (p < 0.001), but there was no significant difference in Notch1 expression between cirrhotic and non-cirrhotic liver tissue (p = 0.197). Notch1 expression was higher in low grade than in high grade HCC (p = 0.036). Notch1 expression showed reverse correlation with mitotic count (p = 0.008), and necrosis (p = 0.005). The disease free survival was shorter in patients displaying low levels of Notch1 expression (p = 0.045). The overall survival showed no significant difference between high and low levels of Notch1 expression; however, it was somewhat longer in patients with high Notch1 expression (p = 0.220). In conclusion, the tumour suppressor role of Notch1 was supported and the use of Notch1 agonists may have a role in improving the prognosis of HCC.