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Background Globally Renal Cell Carcinoma (RCC) represents 3% of malignant tumours in adults and 1.78% in Egypt. AMPK-related protein kinase 5 (ARK5) is mainly associated with a hypoxic microenvironment which is a feature of the major RCC subtypes. Additionally, it displays decreased mitochondrial respiration. SIRT3 is a mitochondrial deacetylase that modifies multiple mitochondrial proteins. Material and methods Fifty eight cases of RCC, and 30 non-neoplastic cases (of End-Stage Kidney Disease (ESKD) were subjected to immunohistochemistry by ARK5 and SIRT3. The results of IHC were correlated together and correlated with the available clinicopathologic and survival data. Results Although no significant difference was detected between RCC and ESKD groups regarding ARK5 expression, there was a significant association with RCC regarding H-score and nucleocytoplasmic expression (both P  = 0.001). Also, SIRT3 was highly expressed in RCC in comparison to the ESKD group (H-score: P  = 0.001). There were significant associations between nucleocytoplasmic ARK5 expression and higher tumour grade, low apoptotic and high mitotic indices, tumour extent, advanced tumour stage, and impaired response of tumours to chemotherapeutic drugs ( P  = 0.039, P  = 0.001, P  = 0.027, P  = 0.011, P  = 0.009, and P  = 0.014 respectively). Moreover, the H score of ARK5 expression showed significant associations with tumour grade, apoptotic and mitotic indices, tumour extension, tumour stage, and response to therapy ( P  = 0.01, 0.035, 0.001, 0.004. 0.003 and 0.013). Regarding SIRT3 expression, it showed significant associations with apoptotic and mitotic indices, tumour extent, tumour stage and response to therapy ( P  = 0.022, 0.02, 0.042, 0.039 and 0.027). Interestingly, there was a highly significant correlation between the expression of ARK5 and SIRT3 ( P  = 0.009). Univariate survival analysis revealed a significant association between short survival duration and both nucleocytoplasmic expression of ARK5 and positive SIRT3 expression ( P  = 0.014 and 0.035). Conclusion ARK5 and SIRT3 are overexpressed in RCC and associated with parameters of poor prognosis as well as short survival. Both seem to influence response to therapy in RCC. So, they could be new targets for therapy that may improve tumour response and patients’ survival. There is a postulated relationship that needs more extensive investigation.

Background: Transurethral resection of tumor is the main treatment of non-muscle-invasive urothelial carcinoma, but it is associated with high rate of recurrence and/or progression and this arouses the need for adjuvant therapy. Topoisomerase II (Top II), KI-67, and P53 are proliferation and cell cycle regulation markers that may predict tumor response to therapy. Aim: This study aimed to assess Top II, KI-67, and P53 expression and their effect on clinical outcome and response to therapy of non-muscle-invasive urothelial carcinoma. Materials and Methods: Fifty cases of non-muscle invasive urothelial carcinoma were collected; Top II, KI-67, and P53 expression was evaluated. Patients received treatment then tumor recurrence was correlated with the expression of previous markers. Results: There was a significant association between high Top II score, P53, and KI-67 and high tumor grade (P = 0.0001, 0.001, and 0.0001), submucosal infiltration (P = 0.0001 and 0.01), and recurrence (P = 0.01, 0.001, and 0.001). Conclusion: Top II, P53, and KI-67 may predict tumor response to therapy and the clinical outcome in non-muscle-invasive urothelial carcinoma.

Background Determination of the extent of involvement or pathological staging is one of the requirements for adequate evaluation of bladder cancer specimens. Therefore, the differentiation between MP and MM is essential for proper treatment and avoiding over or under staging. Aim The present study aimed at evaluation of diagnostic value of smoothelin and vimentin expression both singly and in combination for differentiation between MM and MP. Methods This study was carried out on 59 cystectomy specimens of primary bladder carcinoma and eleven cystoscopic biopsies for non-neoplastic bladder lesions (cystitis). Results Histologically, MM was identified clearly in 40 cases and MP was identified in all 70 examined cases. The cases were immunostained for smoothelin and vimentin. Intensity of smoothelin expression showed significant difference (P = 0.001) between MM and MP with 97.5% sensitivity and 95% specificity and the percentage of smoothelin expression was significantly higher in MP compared to MM (P = 0.001) with 95.7% sensitivity and 85% specificity (using 65% as cut-off point). Vimentin was negative in MP and showed positive expression in 32 cases (80%) of MM with a statistical significant difference (P = 0.001) providing 80% sensitivity and 100% specificity. Combined moderate to strong smoothelin and negative vimentin offered 100% sensitivity and 100% specificity towards the identification of MP. Conclusions Differentiation of MM from MP can be made based on histopathological criteria, which are unfortunately overlapping in many cases. Moderate to strong smoothelin expression with negative vimentin could be very helpful procedure in difficult and overlapping cases with a high diagnostic validity.

Background. Malignant involvement of circumferential resection margin (CRM) and longitudinal resection margin (LRM) after surgical resection of colorectal cancer (CRC) are associated with higher rates of recurrence and development of distant metastasis. This can influence the overall patient’s prognosis. The aim of the current study was to identify pathological factors as predictors for the involvement of resection margins in early T3 CRC. Patients and Methods. Fifty patients radiologically diagnosed to have cT3a/b (CRC) were included in the study. After resection, the pathological examination was performed to identify patients with positive CRM and/or LRM. Relations between the different pathological parameters and the CMR and LRM involvements were assessed. Results. Positive CRM was present in 17 cases (34%), while positive LRM was found in 6 cases (12%). The involvement of both margins was significantly associated with rectal tumors and tumors with infiltrative gross appearance, grade III, deeper invasion, and positive lymph node metastases. Also, there was a significant association between both margins’ positivity and other pathological parameters as signet ring carcinoma, tumor budding, perineural and vascular invasion, high microvessel density (MVD), and sinusoidal vascular pattern, while the presence of necrosis and infiltrative advancing tumor front was significantly associated with CRM involvement only. The depth of tumor invasion and signet ring carcinoma were identified as independent predictor factors for positive CRM and LRM, respectively. Conclusion. Preoperative identification of these pathological parameters can be a guide to tailor the management plan accordingly.

Recently, there has been a surge towards searching for primitive treatment strategies to discover novel therapeutic approaches against multi-drug-resistant pathogens. Endophytes are considered unexplored yet perpetual sources of several secondary metabolites with therapeutic significance. This study aims to isolate and identify the endophytic fungi from Annona squamosa L. fruit peels using morphological, microscopical, and transcribed spacer (ITS-rDNA) sequence analysis; extract the fungus’s secondary metabolites by ethyl acetate; investigate the chemical profile using UPLC/MS; and evaluate the potential antibacterial, antibiofilm, and antiviral activities. An endophytic fungus was isolated and identified as Aspergillus flavus L. from the fruit peels. The UPLC/MS revealed seven compounds with various chemical classes. The antimicrobial activity of the fungal ethyl acetate extract (FEA) was investigated against different Gram-positive and Gram-negative standard strains, in addition to resistant clinical isolates using the agar diffusion method. The CPE-inhibition assay was used to identify the potential antiviral activity of the crude fungal extract against low pathogenic human coronavirus (HCoV 229E). Selective Gram-positive antibacterial and antibiofilm activities were evident, demonstrating pronounced efficacy against both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). However, the extract exhibited very weak activity against Gram-negative bacterial strains. The ethyl acetate extract of Aspergillus flavus L exhibited an interesting antiviral activity with a half maximal inhibitory concentration (IC50) value of 27.2 µg/mL against HCoV 229E. Furthermore, in silico virtual molecular docking-coupled dynamics simulation highlighted the promising affinity of the identified metabolite, orienting towards three MRSA biotargets and HCoV 229E main protease as compared to reported reference inhibitors/substrates. Finally, ADME analysis was conducted to evaluate the potential oral bioavailability of the identified metabolites.

Due to its rising antibiotic resistance and associated inflammations, Helicobacter pylori poses a challenge in modern medicine. Salvia officinalis, a member of the Lamiaceae family, is a promising medicinal herb. In this regard, a phytochemical screening followed by GC-MS and LC-MS was done to evaluate the chemical profile of the total ethanolic extract (TES) and the essential oil, respectively. The anti-H. pylori and the anti-inflammatory activities were evaluated by a micro-well dilution technique and COX-2 inhibition assay. Potential anti-H. pylori inhibitors were determined by an in silico study. The results revealed that the main metabolites were flavonoids, sterols, volatile oil, saponins, and carbohydrates. The LC-MS negative ionization mode demonstrated 12 compounds, while GC-MS showed 21 compounds. Carnosic acid (37.66%), epirosmanol (20.65%), carnosol1 (3.3%), and 12-O-methyl carnosol (6.15%) were predominated, while eucalyptol (50.04%) and camphor (17.75%) were dominant in LC-MS and GC-MS, respectively. TES exhibited the strongest anti-H. pylori activity (3.9 µg/mL) asymptotic to clarithromycin (0.43 µg/mL), followed by the oil (15.63 µg/mL). Carnosic acid has the best-fitting energy to inhibit H. pylori (−46.6769 Kcal/mol). TES showed the highest reduction in Cox-2 expression approaching celecoxib with IC50 = 1.7 ± 0.27 µg/mL, followed by the oil with IC50 = 5.3 ± 0.62 µg/mL. Our findings suggest that S. officinalis metabolites with anti-inflammatory capabilities could be useful in H. pylori management. Further in vivo studies are required to evaluate and assess its promising activity.

Herein, respiratory nitrate reductases (NAR) were utilized in the biosynthesis of zero-valent iron (ZVI) graphene nanocomposite as a simultaneous reducing and capping agent, for the first time, to efficiently adsorb methylene blue (MB) and direct red-81 (DR-81). Under anaerobic conditions, the greenly synthesized graphene was incubated with iron precursor in the presence of crude-NAR enzyme for 48 h to obtain the ZVI graphene composite followed by characterizing this composite using physiochemical analyses. Scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction techniques assured the chemical composition and the interaction between ZVI and graphene. The influences of operating conditions such as contact time, pH and adsorbent dose on the adsorption efficacy were explored in the case of ZVI graphene, graphene and ZVI. ZVI graphene nanocomposite displayed the highest removal efficiency of MB and DR-81 compared to graphene and ZVI-NPs. The removal percentages of DR-81 and MB by ZVI graphene nanocomposites were 88.3 ± 2.66% and 87.6 ± 2.1%, respectively, at pH 7, adsorbent dose 20 mg/50 mL, initial MB or DR-81 concentration of 10 mg/L and shaking speed of 150 rpm. A pseudo first-order model could describe the adsorption kinetics, and the adsorption mechanism was discussed. The promising results of the current study support the potential of the recruitment of ZVI graphene nanocomposites in eliminating various pollutants from industrial effluents on a larger scale. Further, the prepared nanohybrid can be used in other applications such as photocatalysis, Fenton and persulfate activation processes.

Endophytic Aspergillus species represent an inexhaustible source for many medicinally important secondary metabolites. The current study isolated the endophytic Aspergillus niger (OL519514) fungus from Opuntia ficus-indica fruit peels. The antibacterial activities were reported for both Aspergillus species and Opuntia ficus-indica fruit peel extract. Extraction of the endophytic fungal metabolites using ethyl acetate and fractionation was performed, yielding dihydroauroglaucin (C1), isotetrahydroauroglaucin (C2), and cristatumin B (C3). Resistant bacterial strains were used to investigate the efficiency of the total fungal ethyl acetate extract (FEA) and the isolated compounds. FEA showed promising wide spectrum activity. (C3) showed excellent activity against selected Gram-negative resistant bacteria; However, (C2) exhibited tremendous activity against the tested Gram-positive resistant strains; conversely, (C1) possessed the lowest antibacterial activity compared to the two other compounds. An in silico virtual molecular docking demonstrated that cristatumin B was the most active antimicrobial compound against the selected protein targets. In conclusion, the active metabolites newly isolated from the endophytic fungus Aspergillus niger (OL519514) and present in plants’ waste can be a promising antimicrobial agent against multidrug-resistant bacteria.

Eradication of Helicobacter pylori is a challenge due to rising antibiotic resistance and GIT-related disorders. Cuminum cyminum, Pimpinella anisum, and Carum carvi are fruits belonging to the Apiaceae family. Their essential oils were extracted, analyzed using GC-MS, tested for anti-H. pylori activity by a micro-well dilution technique, identified for potential anti-H. pylori inhibitors by an in-silico study, and investigated for anti-inflammatory activity using a COX-2 inhibition assay. Results showed that the main components of C. cyminum, P. anisum, and C. carvi were cumaldehyde (41.26%), anethole (92.41%), and carvone (51.38%), respectively. Essential oil of C. cyminum exhibited the greatest anti-H. pylori activity (3.9 µg/mL) followed by P. anisum (15.63 µg/mL), while C. carvi showed the lowest activity (62.5 µg/mL). The in-silico study showed that cumaldehyde in C. cyminum has the best fitting energy to inhibit H. pylori.C. cyminum essential oil showed the maximum ability to reduce the production of Cox-2 expression approaching celecoxib with IC50 = 1.8 ± 0.41 µg/mL, followed by the C. carvi oil IC50 = 7.3 ± 0.35 µg/mL and then oil of P. anisum IC50 = 10.7±0.63 µg/mL. The investigated phytochemicals in this study can be used as potential adjunct therapies with conventional antibiotics against H. pylori.

Purpose To study the incidence and characteristics of bacillary layer detachment (BALAD) occurring with the two most common choroidal malignancies, choroidal metastasis and choroidal melanoma. Methods A retrospective multicentric record analysis. Eyes with a diagnosis of choroidal melanoma or choroidal metastasis that had good-quality fundus photography and spectral domain optical coherence tomography (OCT) scans of the macular and tumor regions allowing for delineation of the retinal layers were included for analysis. Qualitative image evaluation was done by two independent graders for the presence, location, and OCT features of BALAD, as well as any associated intraretinal or subretinal fluid. Demographic and clinical data were also retrieved. Results Of the 11 eyes with choroidal metastasis and 7 eyes with choroidal melanoma that were included in the final analysis, 6 (54.5%) and 1 (14.3%) had BALAD, respectively. The BALAD co-localized with the subretinal fluid in all cases and with the intraretinal fluid in 1/3 cases (33.3%), was foveal in location in 3 eyes (42.9%), was overlying the tumor in 6 eyes (85.7%), and varied in number and size. Reflectivity within the BALAD was consistently higher than the vitreous and adjacent subretinal fluid, and discernable suspended hyperreflective particles were noted in 5 eyes (71.4%). Conclusion BALAD is relatively common with choroidal metastasis. The OCT features described supplement our recognition of this new entity.