Comparative immune profiling of pancreatic ductal adenocarcinoma progression among South African patients.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer characterized by an immunosuppressive microenvironment. Patients from specific ethnicities and population groups have poorer prognoses than others. Therefore, a better understanding of the immune landscape in such groups is necessary for disease elucidation, predicting patient outcomes and therapeutic targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients of African ancestry. METHODS: Blood samples were obtained from a total of 6 healthy volunteers (HC), 6 Chronic Pancreatitis (CP) and 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC). Real-time Quantitative Polymerase Chain reactions (RT-qPCR), Metabolomics, Enzyme-Linked Immunosorbent Assay (ELISA), Reactive Oxygen Species (ROS), and Immunophenotyping assays were conducted. Statistical analysis was conducted in R (v 4.3.2). Additional analysis of single-cell RNA data from 20 patients (16 PDAC and 4 controls) was conducted to interrogate the distribution of T-cell and Natural Killer cell populations. RESULTS: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD3 T-cell subpopulations (helper and double negative T-cells) decreased when compared to HC. Although both NK (p = 0.014) and NKT (p < 0.001) cell levels increased as the disease progressed, their subsets: NK CD56dimCD16- (p = 0.024) and NKTs CD56+ (p = 0.008) cell levels reduced significantly. Of note is the negative association of NK CD56dimCD16- (p < 0.001) cell levels with survival time. The gene expression analyses showed no statistically significant correlation when comparing the PDAC groups with the controls. The inflammatory status of PDAC was assessed by ROS levels of serum which were elevated in CP (p = 0.025), (RPC (p = 0.003) and LAPC (p = 0.008)) while no significant change was observed in MPC, compared to the HC group. ROS was shown to be positively correlated with GlycA (R = 0.45, p = 0.0096). Single-cell analyses showed a significant difference in the ratio of NKT cells per total cell counts in LAPC (p < 0.001) and MPC (p < 0.001) groups compared with HC, confirming observations in our sample group. CONCLUSION: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.

Initial Experience and Surgical Setup of Robot-Assisted Nephroureterectomy Using the Hugo Robot-Assisted Surgery System.

Introduction and Hypothesis: Robot-assisted radical nephroureterectomy (RANU) has emerged as a valid alternative to open or laparoscopic nephroureterectomy in recent years. However, different types of robotic platforms can limit surgical maneuvers in various ways. This study aimed to describe the surgical procedure and demonstrate RANU's technical feasibility and safety using the Hugo robot-assisted surgery (RAS) system. Materials and Methods: Using the Hugo RAS system, we reported data from the first five consecutive patients who underwent RANU at Tottori University Hospital. We adjusted the docking angles of the four independent arm carts in each case and performed a complete RANU via a transperitoneal approach. We collected patients' sociodemographic and perioperative data, including complications, and compared them retrospectively with data obtained using the da Vinci surgical system. Results: Arms positions were modified after the first patient to be placed all at the back of the patient. Median overall operative time was 283 minutes (203-377) and the median time using the robotic system was 187 minutes (121-277). The median estimated blood loss was 20 mL (5-155). None of the patients required a blood transfusion and none suffered postoperative complications of Clavien-Dindo grade ≥3. These outcomes were similar to those obtained with the da Vinci Xi system. Conclusion: This series represents the first report of RANU executed using the novel Hugo RAS system. Our proposed arm-setup will assist other surgeons and help ensure safe implementation of RANU on the Hugo platform.

Neuroprotective Effects of Glycyrrhiza glabra Total Extract and Isolated Compounds.

Glycyrrhiza glabra L. is a plant commonly utilized in herbal medicine and stands out as one of the more extensively researched medicinal plants globally. It has been documented with respect to several pharmacological activities, notably, neuroprotective effects, among others. However, the neuroprotective activity of pure phenolic compounds has not been reported yet. The chromatographic of a methanolic extract yielded twenty-two compounds, viz.: naringenin 4'-O-glucoside (1), 3',4',7-trihydroxyflavanone (butin) (2), liquiritin (3), liquiritin apioside (4), abyssinone (5), glabrol (6), isoliquiritin (7), neoisoliquiritin (8), isoliquiritin apioside (9), licuraside (10). 3'[O], 4'-(2,2-dimethylpyrano)-3,7-dihydroxyflavanone (11), glabrocoumarin (12), glabrene (13), isomedicarpin (14), 7-hydroxy-4'-methoxyflavone (formononetin) (15), ononin (16), glycyroside (17), (3S)-7,4'-dihydroxy-2'-methoxyisoflavan (18), glabridin (19), neoliquiritin (20), 3,11-dioxooleana-1,12-dien-29-oic acid (21), and 3-oxo-18ß-glycyrrhetinic acid (22). The results of the neuroprotection evaluation showed that G. glabra total extract (TE) and compounds 1, 7, 11, 16, and 20 protected SH-SY5Y cells by inhibiting the depletion of ATP and elevated caspase 3/7 activities induced by MPP+. Indeed, this study reports for the first time the structure and activity of compound 11 and the neuroprotective activity of some phenolic constituents from G. glabra.

Is Stent-Free Ureteroenteric Anastomosis Associated With Lower Ureteroenteric Strictures After Robot-Assisted Radical Cystectomy and Ileal Conduit?

INTRODUCTION: We aimed to investigate the differences in perioperative outcomes, especially ureteroenteric strictures, between patients who underwent a stented ureteroenteric anastomosis at the time of robot-assisted radical cystectomy (RARC) and ileal conduit vs those who did not. METHODS: A retrospective review of our RARC database was performed (2009-2023). Patients were divided into those who received stented ureteroenteric anastomosis vs those who did not. Propensity score matching was performed in the ratio of 3 (stented ureteroenteric anastomosis) to 1 (stent-free) in terms of age, gender, BMI, race, American Society of Anesthesiologists score, neoadjuvant chemotherapy, Charlson Comorbidity Index, prior radiation therapy, previous abdominal surgery history, clinical T3/clinical T4 stage, preoperative metastasis, and preoperative hydronephrosis. A cumulative incidence curve was used to depict ureteroenteric strictures and a Cox regression model was used to identify variables associated with ureteroenteric strictures. RESULTS: Four hundred eighty-eight patients underwent RARC, 366 individuals underwent a stented ureteroenteric anastomosis, and 122 patients underwent a stent-free approach. There was no significant difference in 90-day overall complications, high-grade complications, readmissions, UTIs, leakage, and ileus (P > .05). Ureteroenteric strictures occurred at a rate of 13% and 18% at 1 and 2 years, respectively in the stented group, vs 7% and 10% in the stent-free group (P = .05). Stent placement was significantly associated with ureteroenteric strictures. CONCLUSIONS: Stent-free ureteroenteric anastomosis was associated with fewer strictures following RARC and ileal conduit.

Does Ta Low-grade Urothelial Carcinoma of the Bladder With Focal High-grade Features Carry Worse Prognosis? The Roswell Park Comprehensive Cancer Center Experience.

OBJECTIVE: To describe the management and outcomes of patients with Ta predominantly low-grade urothelial carcinoma with focal high-grade features (FHG) (<5%), compared to those with Ta low grade (LG) and Ta high grade (HG). METHODS: Retrospective review of all patients who underwent transurethral resection of bladder tumor between 2005 and 2023. Patients with Ta disease were identified and categorized into LG, FHG, and HG. Kaplan Meier method was used to depict high-grade recurrence, T-stage progression, and radical cystectomy-free survival. RESULTS: Four hundred forty-nine patients with Ta disease were identified (LG 48%, FHG 12%, and HG 40%). Patients with FHG (32%) had a second-look transurethral resection of bladder tumor more frequently compared to LG (7%) and HG (29%) (P <.01). They received intravesical therapy more frequently compared to LG (36% vs 20%) but lower than HG (55%) (P <.01). They received radical cystectomy less frequently (7% compared to 20% for HG and 11% for LG, P = .01). HG recurrence-free survival at 1, 3, and 5years was HG (68%, 52%, and 43%), FHG (74%, 53%, and 49%), and LG (87%, 79%, and 73%) (log-rank P <.01). T progression-free survival at 1, 3, and 5years was HG (84%, 77%, and 70%), FHG (92%, 82%, and 82%), and LG (94%, 89%, and 85%) (log-rank P = .02). Cystectomy-free survival at 1, 3, and 5years was HG (92%, 84%, and 80%), FHG (96%, 94%, and 94%), and LG (99%, 95%, and 92%) (log-rank P <.01). CONCLUSION: Patients with Ta FHG seem to behave more like Ta HG disease in terms of high-grade recurrences, but they are less likely to experience T-stage progression and convert to cystectomy.

In vitro antibacterial and antioxidant activity of flavonoids from the roots of Tephrosia vogelii: a combined experimental and computational study.

Tephrosia vogelii is a traditional medicinal plant used to treat hypertension, diarrhea and urinary disorders. Silica gel chromatographic separation of CH2Cl2/MeOH (1:1) roots extract of T. vogelii afforded seven compounds namely; ß-sitosterol (1a), stigmasterol (1b), 6a, 12a-dehydro-deguelin (2), tephrosin (3), maackiain (4), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6). GC-MS analysis of essential oils from the root of T. vogelii displayed a total of 17 compounds of which cis-nerolidol (41.7 %) and cadinol (19.7 %) were the major constituents. CH2Cl2/MeOH (1:1) extract, MeOH extract, maackiain (4) and obovatin (5) showed moderate inhibitory activity against Pseudomonas aeruginosa with MIC value of 0.5, 0.66, 0.83 and 0.83 mg/mL, respectively, compared to ciprofloxacin (MIC of 0.078 µg/mL). 6a, 12a-dihydro-deguelin (2), and 6-oxo, 6a, 12a-dehydro-deguelin (6) displayed significant activity against S. epidermis with MIC values of 0.66 mg/mL. Tephrosin (3) and maackiain (4) also showed moderate antibacterial activity against Staphylococcus aureus and Proteus mirabilis with MIC values of 0.83 and 0.5 mg/mL, respectively, compared to ciprofloxacin (0.312 µg/mL). The radical scavenging activity results indicated that tephrosin (3), obovatin (5) and 6-oxo, 6a, 12a-dehydro-deguelin (6) showed potent DPPH scavenging activity with IC50 values of 10.97, 10.43 and 10.73 µg/mL, respectively, compared to ascorbic acid (IC50 of 5.83 µg/mL). The docking prediction results revealed that 6a, 12a-dehydro-deguelin (2) displayed the best binding energy of -8.1 kcal/mol towards pyruvate kinase of S. aureus (PDB ID: 3T07) and -7.9 kcal/mol towards P. mirabilis urease (PDB ID: 1E9Y) and DNA gyrase B of Escherichia coli (PDB: 4F86) receptors compared to ciprofloxacin (-7.2 to -8.0 kcal/mol). Maackiain (4) and obovatin (5) displayed the minimum binding energy of -7.9 and -8.2 kcal/mol towards the LasR protein of P. aeruginosa (PDB: ID 2UV) and S. epidermidis FtsZ (PDB: ID 4M8I), respectively. The SwissADME drug-likeness and Pro Tox II toxicity prediction results indicated that compounds (2-6) obeyed Lipinski's rule of five with 0 violations and none of them were found to be hepatotoxic, mutagenic, and cytotoxic, respectively. The in vitro assessment results supported by the in silico analysis revealed that crude extracts and isolated compounds showed promising antibacterial and antioxidant activity, which proves the therapeutic potential of the roots of T. vogelii.

Anticancer diterpenes of African natural products: Mechanistic pathways and preclinical developments.

BACKGROUND: The African continent is home to five biodiversity hotspots, boasting an immense wealth of medicinal flora, fungi and marine life. Diterpenes extracted from such natural products have compelling cytotoxic activities that warrant further exploration for the drug market, particularly in cancer therapy, where mortality rates remain elevated worldwide. PURPOSE: To demonstrate the potential of African natural products on the global stage for cancer therapy development and provide an in-depth analysis of the current literature on the activity of cancer cytotoxic diterpenes from African natural sources (to our knowledge, the first of its kind); not only to reveal the most promising candidates for clinical development, but to demonstrate the importance of preserving the threatened ecosystems of Africa. METHODS: A comprehensive search by means of the PRISMA strategy was conducted using electronic databases, namely Web of Science, PubMed, Google Scholar and ScienceDirect. The search terms employed were 'diterpene & mechanism & cancer' and 'diterpene & clinical & cancer'. The selection process involved assessing titles in English, Portuguese and Spanish, adhering to predefined eligibility criteria. The timeframe for inclusion spanned from 2010 to 2023, resulting in 218 relevant papers. Chemical structures were visualized using ChemDraw 21.0, PubChem was utilized to search for CID numbers. RESULTS: Despite being one of the richest biodiverse zones in the world, African natural products are proportionally underreported compared to Asian countries or otherwise. The diterpenes andrographolide (Andrographis paniculata), forskolin (Coleus forskohlii), ent-kauranes from Isodon spp., euphosorophane A (Euphorbia sororia), cafestol & kahweol (Coffea spp.), macrocylic jolkinol D derivatives (Euphorbia piscatoria) and cyathane erinacine A (Hericium erinaceus) illustrated the most encouraging data for further cancer therapy exploration and development. CONCLUSIONS: Diterpenes from African natural products have the potential to be economically significant active pharmaceutical and medicinal ingredients, specifically focussed on anticancer therapeutics.

Green Synthesis of Gold Nanoparticles Using Liquiritin and Other Phenolics from Glycyrrhiza glabra and Their Anti-Inflammatory Activity.

Phenolic compounds are the main phytochemical constituents of many higher plants. They play an important role in synthesizing metal nanoparticles using green technology due to their ability to reduce metal salts and stabilize them through physical interaction/conjugation to the metal surface. Six pure phenolic compounds were isolated from licorice (Glycyrrhiza glabra) and employed in synthesizing gold nanoparticles (AuNPs). The isolated compounds were identified as liquiritin (1), isoliquiritin (2), neoisoliquiritin (3), isoliquiritin apioside (4), liquiritin apioside (5), and glabridin (6). The synthesized AuNPs were characterized using UV, zeta sizer, HRTEM, and IR and tested for their stability in different biological media. The phenolic isolates and their corresponding synthesized NP conjugates were tested for their potential in vitro cytotoxicity. The anti-inflammatory effects were investigated in both normal and inflammation-induced settings, where inflammatory biomarkers were stimulated using lipopolysaccharides (LPSs) in the RAW 264.7 macrophage cell line. LPS, functioning as a mitogen, promotes cell growth by reducing apoptosis, potentially contributing to observed outcomes. Results indicated that all six pure phenolic isolates inhibited cell proliferation. The AuNP conjugates of all the phenolic isolates, except liquiritin apioside (5), inhibited cell viability. LPS initiates inflammatory markers by binding to cell receptors and setting off a cascade of events leading to inflammation. All the pure phenolic isolates, except isoliquiritin, neoisoliquiritin, and isoliquiritin apioside inhibited the inflammatory activity of RAW cells in vitro.

The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: Data from the International Robotic Cystectomy Consortium.

OBJECTIVE: To assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 988 patients who underwent RARC (2004-2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). RESULTS: A total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). CONCLUSION: Our data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH.

In vitro antimicrobial and antioxidant activities, essential oil composition, and in silico molecular modeling analysis of secondary metabolites from roots of Verbascum sinaiticum.

Verbascum sinaiticum is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from V. sinaiticum. The 1H-NMR, 13C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3'-(4''-methoxy phenyl)-3'-oxo-propionyl hexadecanoate (1), harpagoside (2), pulverulentoside I (3), scrophuloside B4 (4), scropolioside A (5), scropolioside-D2 (6), and harpagide 6-O-ß-glucoside (7), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to Streptococcus agalactiae, with a 2 mg/mL MIC. The EO from roots was effective against Candida albicans and Trichophyton mentagrophytes, with a MIC of 8 mg/mL. The MeOH and CH2Cl2/CH3OH (1:1) root extracts showed the maximum activity against S. epidermidis with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against Staphylococcus epidermidis, which exhibited a 0.0625 mg/mL MIC for compound 1. The strongest radical scavenging activity was exhibited by the methanol extract (IC50 = 3.4 µg/mL), and compounds 4, 6, 5, 3, 7, and 2 with IC50 values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 µg/mL, respectively, in comparison with ascorbic acid (IC50 = 1.3 µg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from -38.5 to -43.1 kJ/mol, -33.1 to -42.7 kJ/mol, -34.7 to -39.3.7 kJ/mol, -25.5 to -37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase IIß (PDB ID: 4fm9), S. epidermidis FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the in vitro antibacterial activity are in good agreement. These findings show that the isolated compounds 2-7 can act as potential antioxidants and strong antibacterials against Staphylococcus aureus and S. epidermidis. As a result, V. sinaiticum root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plant's potential candidate.

Approaches for Stereotactic Radiosurgery (SRS)/Stereotactic Radiotherapy (SRT) in brain metastases using different radiotherapy modalities (Feasibility study).

BACKGROUND: SRS and SRT are precise treatments for brain metastases, delivering high doses while minimizing doses to nearby organs. Modern linear accelerators enable the precise delivery of SRS/SRT using different modalities like three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and Rapid Arc (RA). OBJECTIVE: This study aims to compare dosimetric differences and evaluate the effectiveness of 3DCRT, IMRT, and Rapid Arc techniques in SRS/SRT for brain metastases. METHODS: 10 patients with brain metastases, 3 patients assigned for SRT, and 7 patients for SRS. For each patient, 3 treatment plans were generated using the Eclipse treatment planning system using different treatment modalities. RESULTS: No statistically significant differences were observed among the three techniques in the homogeneity index (HI), maximum D2%, and minimum D98% doses for the target, with a p > 0.05. The RA demonstrated a better conformity index of 1.14±0.25 than both IMRT 1.21±0.26 and 3DCRT 1.37±0.31. 3DCRT and IMRT had lower Gradient Index values compared to RA, suggesting that they achieved a better dose gradient than RA. The mean treatment time decreased by 26.2% and 10.3% for 3DCRT and RA, respectively, compared to IMRT. In organs at risk, 3DCRT had lower maximum doses than IMRT and RA, but some differences were not statistically significant. However, in the brain stem and brain tissues, RA exhibited lower maximum doses compared to IMRT and 3DCRT. Additionally, RA and IMRT had lower V15Gy, V12Gy, and V9Gy values compared to 3DCRT. CONCLUSION: While 3D-CRT delivered lower doses to organs at risk, RA and IMRT provided better conformity and target coverage. RA effectively controlled the maximum dose and irradiated volume of normal brain tissue. Overall, these findings indicate that 3DCRT, RA, and IMRT are suitable for treating brain metastases in SRS/SRT due to their improved dose conformity and target coverage while minimizing dose to healthy tissues.

Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer.

Nowadays, breast cancer is considered one of the most upsetting malignancies among females. Encapsulation of celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles (NPs) produce homogenous and spherical nanoparticles with good encapsulation efficiencies (EE %) and bioavailability. In vitro cytotoxicity study conducted on human breast cancer MDA-MB-231 cell lines revealed that there was a significant decline in the IC50 for encapsulated drugs when compared to each drug alone or their free combination. In addition, results demonstrated that there is a synergism between CXB and PDG as their combination indices were 0.62251 and 0.15493, respectively. Moreover, results of scratch wound healing assay revealed enhanced antimigratory effect of free drugs and fabricated NPs in comparison to untreated cells. Furthermore, In vitro results manifested that formulated nanoparticles exhibited induction of apoptosis associated with reduced angiogenesis, proliferation, and inflammation. In conclusion, nanoencapsulation of multiple drugs into nanoparticles might be a promising approach to develop new therapies for the managing of triple negative breast cancer.

The Molluscicidal Activity of Green Synthesized Copper Oxide-Based Annona squamosa Seed Extract Nanoparticles on the Feeding Behavior, Biochemical, Molecular, and Immunohistochemical Alterations of Biomphalaria alexandrina Snails.

Because of their low ecological impact, plant molluscicides have garnered much attention. The work aimed to find out if Annona squamosa (AS) seed extract has a molluscicidal impact on Biomphalaria alexandrina snails and enhances this extract by adding CuO nanoparticles (NPs). Using a scanning electron microscope (SEM), transmission electron microscope (TEM), and PANalytical X'Pert PRO X-ray diffractometer (XRD), the presence of the green A. squamosa-based CuO NPs (AS-CuO NPs) was confirmed. After 24 h of exposure, the half-lethal concentration (LC50) of AS-CuO NPs was more toxic to mature B. alexandrina than the aqueous extract of AS seeds (LC50: 119.25 mg/L vs. 169.03 mg/L). The results show that snails exposed to sublethal doses of AS-CuO NPs at LC10 or LC25 (95.4 or 106.7 mg/L, respectively) had much higher glucose levels and alkaline phosphatase activity than those not exposed. Nevertheless, there was no discernible change in the protein content in general or glycogen phosphorylase production. Histological and immunohistochemical analysis showed that snails exposed to A. squamosa-derived CuO NPs LC10 had shrinking digestive tubules and degeneration as well as vacuolation of many digestive, secretory, ova, and sperm cells, with PCNA expressing positively in the hermaphrodite gland and digestive tubule cells. The toxic profile of green CuO NPs produced by A. squamosa may damage the biological activity of B. alexandrina snails; thus, this compound could be used as a molluscicidal base. Furthermore, B. alexandrina proved to be a useful biomarker of nanomaterial contamination.

The ability of digital breast tomosynthesis to reduce additional examinations in older women.

Aims: To assess the diagnostic performance of digital breast tomosynthesis (DBT) in older women across varying breast densities and to compare its effectiveness for cancer detection with 2D mammography and ultrasound (U/S) for different breast density categories. Furthermore, our study aimed to predict the potential reduction in unnecessary additional examinations among older women due to DBT. Methods: This study encompassed a cohort of 224 older women. Each participant underwent both 2D mammography and digital breast tomosynthesis examinations. Supplementary views were conducted when necessary, including spot compression and magnification, ultrasound, and recommended biopsies. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated for 2D mammography, DBT, and ultrasound. The impact of DBT on diminishing the need for supplementary imaging procedures was predicted through binary logistic regression. Results: In dense breast tissue, DBT exhibited notably heightened sensitivity and NPV for lesion detection compared to non-dense breasts (61.9% vs. 49.3%, p < 0.001) and (72.9% vs. 67.9%, p < 0.001), respectively. However, the AUC value of DBT in dense breasts was lower compared with non-dense breasts (0.425 vs. 0.670). Regarding the ability to detect calcifications, DBT demonstrated significantly improved sensitivity and NPV in dense breasts compared to non-dense breasts (100% vs. 99.2%, p < 0.001) and (100% vs. 94.7%, p < 0.001), respectively. On the other hand, the AUC value of DBT was slightly lower in dense breasts compared with non-dense (0.682 vs. 0.711). Regarding lesion detection for all cases between imaging examinations, the highest sensitivity was observed in 2D mammography (91.7%, p < 0.001), followed by DBT (83.7%, p < 0.001), and then ultrasound (60.6%, p < 0.001). In dense breasts, sensitivity for lesion detection was highest in 2D mammography (92.9%, p < 0.001), followed by ultrasound (76.2%, p < 0.001), and the last one was DBT. In non-dense breasts, sensitivities were 91% (p < 0.001) for 2D mammography, 50.7% (p < 0.001) for ultrasound, and 49.3% (p < 0.001) for DBT. In terms of calcification detection, DBT displayed significantly superior sensitivity compared to 2D mammography in both dense and non-dense breasts (100% vs. 91.4%, p < 0.001) and (99.2% vs. 78.5%, p < 0.001), respectively. However, the logistic regression model did not identify any statistically significant relationship (p > 0.05) between DBT and the four dependent variables. Conclusion: Our findings indicate that among older women, DBT does not significantly decrease the requirement for further medical examinations.

The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer.

INTRODUCTION: We sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. METHODS: Retrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010-2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. RESULTS: Seven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60-27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18-0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94-0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10-1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08-0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01-0.09, P < 0.0001) were associated with receipt of AS. CONCLUSION: AS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.

Does the urinary microbiome profile change after treatment of bladder cancer?

INTRODUCTION: We sought to investigate the change in the urinary microbiome profile after transurethral resection of bladder tumor (TURBT). METHODS: Urine specimens were collected from consecutive patients with bladder cancer. Patients were divided into those with bladder tumors ("Tumor group": de novo tumors or recurrent/progressed after TURBT ± intravesical therapy) versus those without evidence of recurrence after treatment "No Recurrent Tumor group". Samples were analyzed using 16S rRNA sequencing. Alteration in the urinary microbiome was described in terms of alpha (diversity within a sample measured by Observed, Chao, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Brady Curtis Diversity index), and differential abundance of bacteria at the genus level. Analyses were adjusted for gender, method of preservation (frozen vs preservative), and method of collection (mid-stream vs. catheter). RESULTS: Sixty-eight samples were analyzed (42 in "Tumor" vs 26 in "No Recurrent Tumor" groups). The median age was 70 years (IQR 64-74) and 85% were males. All patients in the "No Recurrent Tumor" group had non-muscle invasive bladder cancer and 85% received BCG compared to 69% and 43% for the "Tumor" group, respectively. There was no significant difference in alpha diversity (p > 0.05). Beta diversity was significantly different (p = 0.04). Veillonella and Bifidobacterium were more abundant in the "Tumor" group (> 2FC, p = 0.0002), while Escherichia-Shigella (> 2FC, p = 0.0002) and Helococcus (> 2FC, p = 0.0008) were more abundant in the "No Recurrent Tumor" group. CONCLUSION: Bladder cancer patients with no recurrence and/or progression exhibited a different urinary microbiome profile compared to those with tumors.

Methoxylated Flavonols and ent-Kaurane Diterpenes from the South African Helichrysum rutilans and Their Cosmetic Potential.

Chromatographic fractionation of a methanol extract of Helichrysum rutilans afforded seven known compounds. The isolated compounds were identified as 5,7,8-trihydroxy-3,6-dimethoxyflavone-8-O-2-methyl-2-butanoate (C-1), 5,7-dihydroxy-3,6,8-trimethoxyflavone (C-2), 5-hydroxy-3,6,7,8-tetramethoxyflavone (C-3), 5-hydroxy-3,6,7-trimethoxyflavone (C-4), ent-kaurenoic acid (C-5), ent-kauran-18-al (C-6), and 15-α-hydroxy-(-)-ent-kaur-16-en-19-oic acid (C-7). Compounds C-1-C-4 demonstrated high antioxidant capacities on ORAC hydroxyl radical (2.114 ± 4.01; 2.413 ± 6.20; 1.924 ± 16.40; 1.917 ± 3.91) × 106; ORAC peroxyl radical (3.523 ± 3.22; 2.935 ± 0.13; 2.431 ± 8.63; 2.814 ± 5.20) × 103 µMTE/g; and FRAP (1251.45 ± 4.18; 1402.62 ± 5.77) µMAAE/g, respectively. Moderate inhibitory activities against Fe2+-induced lipid peroxidation were observed for C-1-C-4 as IC50 values of 13.123 ± 0.34, 16.421 ± 0.92, 11.64 ± 1.72, 14.90 ± 0.06 µg/mL, respectively, while their respective anti-tyrosinase activities with IC50 values of 25.735 ± 9.62, 24.062 ± 0.61, 39.03 ± 13.12, 37.67 ± 0.98 µg/mL were also observed. All compounds demonstrated TEAC values within the range of 1105-1424 µMTE/g. The result is an indication that a methanol extract of H. rutilans might possibly be a good source of natural antioxidants against ailments caused by cellular oxidative stress and as inhibitors against skin depigmentation, as well as possible raw materials needed for slowing down perishable agricultural products. This is the first report on the phytochemical and biological evaluation of H. rutilans.

Does testosterone replacement therapy increase the risk of conversion to treatment in patients with prostate cancer on active surveillance?

PURPOSE: We aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer (CaP) who elected active surveillance (AS). METHODS: A retrospective review of our CaP database was performed. Patients who received TRT while on AS were identified and were matched to a cohort of patient on AS while not on TRT (1:3) using propensity score matching. Treatment-free survival (TFS) was computed using Kaplan Meier method. Multivariable Cox regression model was used to evaluate variables associated with treatment. RESULTS: Twenty-four patients in the TRT group were matched to 72 patients without TRT. Median follow-up was 5.82 years (IQR 3.27-9.30). There was no significant difference in conversion to treatment (24% vs. 21%, P = 1.00) There was no significant difference in TFS (log rank P = 0.87). Prostate specific antigen (PSA) density was the only variable associated TFS (HR 1.08, 95%CI 1.03-1.13, P = 0.001). CONCLUSION: TRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS.

Green-Synthesized Silver Nanoparticles: Antifungal and Cytotoxic Potential for Further Dental Applications.

Fungal infections caused by Candida albicans (C. albicans) are one of the most prevalent types of oral disorders in the elderly. It has been reported that drug resistance to fungal pathogens poses a severe risk to global healthcare systems and public health. Therefore, the goal of this work is to investigate the cytotoxic and antifungal properties of silver nanoparticles (AgNPs) produced using three different natural extracts: Berzelia lanuginose, Helichrysum cymosum, and Searsia crenata. According to the UV-Vis results, the synthesized AgNPs via B. lanuginose, H. cymosum, and S. crenata show surface plasmonic resonance (SPR) peaks at 430, 440, and 428 nm, respectively. HR-TEM revealed different shapes for the nanoparticles within the size ranges of 16-20, 31-60, and 57-72 nm for B. lanuginose, H. cymosum, and S. crenata, respectively. Using a human oral fibroblast cell line, the cytotoxicity of both AgNPs and plant extracts was tested at concentrations of 0.007, 0.012, 0.025, and 0.062 mg/mL (buccal mucosa fibroblasts). The antifungal activity showed growth inhibition zones of approximately 18 mm, 18.67 mm, and 18.33 mm for the AgNPs conjugated with B. lanuginose, H. cymosum, and S. crenata, respectively. For the studied samples, the minimum inhibitory concentration (MIC50) was less than 0.015 mg/mL. The AgNPs exhibited antifungal activity that was concentration- and size-dependent. The results of this study offer new insights into the cytotoxicity and antifungal activity of the green-synthesized AgNPs.

Carbon dots labeled Lactiplantibacillus plantarum: a fluorescent multifunctional biocarrier for anticancer drug delivery.

A carbon dots (CDs)-biolabeled heat-inactivated Lactiplantibacillus plantarum (HILP) hybrid was investigated as a multifunctional probiotic drug carrier with bioimaging properties using prodigiosin (PG) as anticancer agent. HILP, CDs and PG were prepared and characterized using standard methods. CDs-labeled HILP (CDs/HILP) and PG loaded CDs/HILP were characterized by transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and for entrapment efficiency (EE%) of CDs and PG, respectively. PG-CDs/HILP was examined for stability and PG release. the anticancer activity of PG-CDs/HILP was assessed using different methods. CDs imparted green fluorescence to HILP cells and induced their aggregation. HILP internalized CDs via membrane proteins, forming a biostructure with retained fluorescence in PBS for 3 months at 4°C. Loading PG into CDs/HILP generated a stable green/red bicolor fluorescent combination permitting tracking of both drug carrier and cargo. Cytotoxicity assay using Caco-2 and A549 cells revealed enhanced PG activity by CDs/HILP. LCSM imaging of PG-CDs/HILP-treated Caco-2 cells demonstrated improved cytoplasmic and nuclear distribution of PG and nuclear delivery of CDs. CDs/HILP promoted PG-induced late apoptosis of Caco-2 cells and reduced their migratory ability as affirmed by flow cytometry and scratch assay, respectively. Molecular docking indicated PG interaction with mitogenic molecules involved in cell proliferation and growth regulation. Thus, CDs/HILP offers great promise as an innovative multifunctional nanobiotechnological biocarrier for anticancer drug delivery. This hybrid delivery vehicle merges the physiological activity, cytocompatibility, biotargetability and sustainability of probiotics and the bioimaging and therapeutic potential of CDs.