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Background: No consensus has been reached on the adequate dose of mitomycin C (MMC) in XEN45 gel stent implantation. Lower doses have the potential to reduce MMC‐linked side effects. This study aimed to evaluate treatment efficacy of ab interno XEN45 gel stent in primary open‐angle glaucoma (POAG) with three different MMC doses. Methods: This retrospective single‐centre nonrandomised trail included 54 patients (56 eyes) who underwent XEN45 gel stent implantation for POAG with above‐target intraocular pressure (IOP) under medical therapy. Eyes were grouped according to the received MMC dose: Group 1 (20 μg; n = 21), Group 2 (10 μg; n = 14) and Group 3 (5 μg; n = 21). The primary endpoint was the mean IOP change in the three MMC dose groups after 6, 12 and 24 months. Secondary endpoints included the success rate defined as lowering of baseline IOP ≥ 20% and below a cut‐off IOP set at three different levels: ≤ 18, ≤ 16 and ≤ 14 mmHg (Criteriums 1, 2 and 3), the mean number of ocular hypotensive medications and the frequency of needling procedures. Results: After 24 months, the overall mean (standard error) IOP was significantly reduced from 24.7 (0.9) mmHg to 15.2 (0.7) mmHg (p < 0.0001). The average IOP change (standard error) in MMC dose groups 1, 2 and 3 was −8.6 (2) mmHg, −10.1 (2.1) mmHg and −10.4 (2.8) mmHg. Complete success (Criterium 1) was achieved in 50%, 62% and 43% of the eyes in groups 1, 2 and 3. No statistically significant difference was found within the first 24 months between the three MMC dose groups for IOP change, success rate, number of ocular hypotensive medications and the frequency of needling procedures. Conclusions: XE45 was effective in all three dose groups. As the success rate did not significantly differ between the MMC doses, these results may support the use of the lowest dose. Trial Registration: ClinicalTrials.gov identifier: 559/2016BO2 [ABSTRACT FROM AUTHOR]

This study aimed to optimize the production of carotenoid pigments from Micrococcus luteus (ATCC 9341) through the statistical screening of media components and the characterization of antimicrobial, antioxidant, cytogenetic and cytotoxic activities. A BOX-Behnken design was used to assess the effects of whey concentration, inoculum size, pH, temperature, and agitation speed on carotenoid yield. The optimum combination increased production to 2.19 g/L, with a productivity of 0.045 g L-1 h−1 and a productivity yield of 0.644 g/g, as confirmed by an observed carotene production of 2.19 g/L. The final response surface model fitting the data had an R2 of 0.9461. High-performance liquid chromatography (HPLC) analysis identified 12 carotenoid pigment compounds produced by M. luteus. The extracts displayed moderate antimicrobial efficacy against Gram-positive bacteria such as Bacillus cereus (ATCC 11778), Staphylococcus aureus (ATCC 6538), and E. faecalis (ATCC 19433), with inhibition zone diameters (IZD) of 29.0, 14.0, and 37.0 mm, respectively, at 1000 μg/mL. However, its effectiveness against Gram-negative bacteria is limited. In comparison, tetracycline exhibited greater antimicrobial potency. The IC50 value of carotenoids was used to indicate the antioxidant activity. IC50 value from the DPPH assay was 152.80 mg/100mL. An IC50 cytotoxicity value greater than 300 μg/mL was found against normal mouse liver cells, with over 68% cell viability even at 300 μg/mL, indicating low toxicity. Histological structure studies revealed normal myocardial muscle tissue, lung tissue, and kidney tissue sections, whereas liver tissue sections revealed ballooning degeneration of hepatocytes and disorganization of hepatic cords. Cytogenetic parameters revealed that the carotene treatment group had a mitotic index (70%) lower than that of the control but higher than that of the positive control, mitomycin, and did not substantially increase numerical (1.2%) or structural aberrations compared with those of the control, suggesting a lack of genotoxic effects under the experimental conditions. In conclusion, optimized culture conditions enhanced carotenoid yields from M. luteus, and the extracts displayed promising bioactivity as moderate antibiotics against certain gram-positive bacteria and as antioxidants. The high IC50 values demonstrate biosafety. Overall, this bioprocess for enhanced carotenoid production coupled with bioactivity profiling and low cytotoxicity support the application of M. luteus carotenoids. [ABSTRACT FROM AUTHOR]

Objectives: To investigate tear function and ocular surface disease (OSD) findings in patients with glaucoma who received antiglaucoma medication in one eye and trabeculectomy surgery in the other eye. Materials and Methods: The patient group included 38 eyes of 19 patients who had undergone trabeculectomy surgery with mitomycin C (MMC) treatment in one eye at least 6 months prior. These eyes were followed up without medication while the fellow eye continued receiving antiglaucomatous medication. The control group comprised 20 eyes of 20 healthy individuals. Demographic data, follow-up period after trabeculectomy, antiglaucoma medications, number of drops per day, and duration of medication were recorded. Tear break-up time (BUT), corneal and conjunctival fluorescein staining, Schirmer II test, and conjunctival impression cytology were performed. Results: A statistically significant difference was observed in BUT, corneal and conjunctival fluorescein staining, Schirmer II test, and Nelson staging levels in both eyes of patients with glaucoma compared to the control group (p=0.05). Although not statistically significant, BUT, Schirmer II test, punctate staining, and Nelson staging results showed improvement with increasing postoperative time. Conclusion: In our patient group, antiglaucoma medications and trabeculectomy surgery with MMC induced OSD to a similar degree. No superiority was observed between trabeculectomy with MMC and antiglaucoma drops in terms of OSD incidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell carcinoma of the anus or anal cancer is increasing in prevalence, and the standard treatment of mitomycin and 5-fluorouracil is too toxic for many patients. Unfortunately, there is currently no standard of care for what to do for this disease when someone is not a candidate for this aggressive treatment. Here, we demonstrate the promising preliminary toxicity profile and efficacy of the combination of weekly carboplatin and paclitaxel chemotherapy for patients with localized anal cancer. This regimen was able to complete 80% of the intended treatments with anticipated toxicities, and 89% achieved a complete clinical response. This combination is a promising regimen and is already being investigated further in a clinical trial. Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To determine the survival benefit and immunomodulatory effects of cimetidine pre-, peri- or post-operatively in patients with colorectal cancer (CRC). Methods: A systematic review was conducted using PubMed and Cochrane Library to retrieve randomized control trials (RCTs) that investigated the effects of cimetidine on survival and immunomodulation via improvement in tumor infiltrating lymphocytes (TILs) and peripheral blood lymphocytes. The review was carried out in accordance with the extended Preferred Reporting Items for Systematic Reviews and Meta-analyses. Results: Four studies with the total of 267 patients were included in this systematic review. Treatment duration varied from 5 days to 1 year. Two studies reported a significant TIL response in the resected specimens after administering cimetidine, while one RCT showed an escalation of CD3, CD4 and CD57 lymphocytes in peripheral blood compared to the baseline following cimetidine treatment (p < 0.01). Of the three trials that examined the effects of cimetidine on survival, only two studies revealed significant survival benefit while the remaining study only showed a trend towards survival benefit. Conclusion: Repurposing of existing drugs like cimetidine has a potential to offer a survival benefit by acting as an immunomodulatory agent in patients undergoing curative resection for CRC. However, the heterogeneity seen in current studies and the evolvement of adjunctive therapies for CRC warrant large-scale, well-designed prospective RCTs to establish the efficacy of cimetidine in CRC. [ABSTRACT FROM AUTHOR]

Chrysin is hypothesized to possess the ability to prevent different illnesses, such as diabetes, cancer, and neurodegenerative disorders. Nonetheless, chrysin has a low solubility under physiological conditions, resulting in limited bioavailability. In a previous study, we utilized an oil-in-water emulsion system (chrysin-ES or chrysin-NE) to encapsulate chrysin, thereby increasing its bioaccessibility and preserving its antioxidant and anti-Alzheimer's properties. To promote the chrysin-ES as a supplementary and functional food, it was obligatory to carry out a safety assessment. Cytotoxicity testing showed that chrysin-ES was harmless, with no killing effect on 3T3-L1 (adipocytes), RAW 264.7 (macrophages), HEK293 (kidney cells), and LX-2 (hepatic stellate cells). The acute toxicity evaluation demonstrated that the 50% lethal dose (LD50) for chrysin-ES was greater than 2000 mg/kg BW. Genotoxicity assessments found that chrysin-ES did not induce DNA mutations in vitro or in vivo. Furthermore, chrysin and chrysin-ES exhibited anti-mutagenic properties against PhIP-induced and IQ-induced mutagenesis in the Ames test, while they inhibited urethane-, ethyl methanesulfonate-, mitomycin C-, and N-nitrosomethylurea-mediated mutations in Drosophila. The present study illustrates the safety and anti-genotoxicity properties of chrysin-ES, allowing for the further development of chrysin-based food supplements and nutraceuticals. [ABSTRACT FROM AUTHOR]

The article focuses on congenital laryngeal webs, a rare malformation resulting from embryonic laryngeal recanalization failure, with less than 5 present of congenital laryngeal anomalies. Topics include the anatomical location and etiology of laryngeal webs, presenting symptoms such as hoarseness and respiratory distress, and a case report detailing a 6-year-old with unrecognized laryngeal web misdiagnosed as laryngopharyngeal reflux and vocal cord paresis.

Purpose: To investigate gel stent implantation with and without intraoperative sustained-release mitomycin C (MMC SR) in a rabbit model for gel stent implantation, and to examine aqueous humor outflow (AHO) postimplantation. Methods: Four groups of rabbits were included. Group 1 was untreated (control). Groups 2, 3, and 4 received the gel stent without MMC, with MMC solution (subconjunctival injection), and with MMC SR (subconjunctival injection), respectively. Intraocular pressure (IOP) and AHO were assessed via tonometry and indocyanine green-based angiography, respectively. The main efficacy measure was change in IOP from baseline. Results: Following gel stent implantation, Groups 2, 3, and 4 maintained ≥20% IOP reduction (response) for a median duration of 1 week, 6.5 weeks, and 30 weeks, respectively. Angiography showed normal aqueous humor drainage (Group 1) beginning at the perilimbal trabecular plexus and continuing posteriorly to episcleral outflow vessels. Following implantation, drainage occurred preferentially and directly into the subconjunctival bleb. Conclusions: Gel stent implantation with MMC SR was most effective in achieving sustained, long-term IOP reduction in the rabbit model, compared with implantation with or without MMC solution. Bleb presence and the postimplantation aqueous angiography results indicated redirection of the AHO to the subconjunctival vasculature and presumed lymphatics, suggesting efficient glaucoma filtration to lower IOP in this model. This rabbit model and aqueous angiography may help refine understanding of the mechanism of action of minimally invasive glaucoma surgeries and ultimately translate to improved surgical devices and procedures for patients with glaucoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment of non-muscle invasive bladder cancer (NMIBC) consists mainly of repeated transurethral bladder surgery (TURBs) and instillation treatments. This treatment might influence bladder function and, therefore, the patient's quality of life. We used bladder-related medication as a surrogate marker of compromised bladder function to investigate whether the load of repeated surgery and the exposure to adjuvant instillation influence bladder function. The study was conducted as a register-based study in a non-selected national cohort of NMIBC patients. We included 17,774 patients. Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB and a higher risk of cystitis. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed and had a higher risk of cystitis. Repeated TURBs have the highest impact on bladder function. To maintain the best possible bladder function, the goal of NMIBC treatment should be as few TURBs as feasible. Repeated transurethral bladder resections (TURBs) and instillation treatments in non-muscle invasive bladder cancer (NMIBC) might influence bladder function and, therefore, quality of life. Bladder-related medication is a surrogate marker of compromised bladder function. The objective was to investigate whether TURBs and adjuvant instillation therapy are associated with the use of anticholinergics, β3-agonists, and cystitis-relevant antibiotics. We divided all Danish patients diagnosed with primary NMIBC during 2002–2017 registered in the Danish National Patient Registry (DNPR) based on TURB-load within the first five years from diagnosis (1 TURB, 2–4 TURBs, ≥5 TURBs). Instillation therapy with either mitomycin C (MMC) or bacillus Calmette-Guerin vaccine (BCG) was independent exposure (yes or no). We included 17,774 patients; 76% men, median age: 70 years (IQR: 63, 77). Patients exposed to ≥5 TURBs had a higher risk of using bladder-relaxing medication than patients exposed to 1 TURB, HR = 4.01 [3.33; 4.83], and higher risk of cystitis, HR = 2.27 [2.05; 2.51]. BCG-exposed patients had a higher risk of bladder-relaxing medication use compared to non-exposed, HR = 1.92 [1.69; 2.18], and a higher risk of cystitis, HR = 1.39 [1.31; 1.48]. Repeated TURBs have the highest impact on bladder function. Adjuvant instillation therapy is also associated with the use of bladder-related medication. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumours of the lining of the kidney and its drainage tube (the ureter) can be treated by surgery carried out through fine telescopes. There is an increased risk of tumours growing back after such surgery. One of the ways to reduce the risk is to put medications such as chemotherapy into the kidney to treat the lining and tumours on it. The location and structure of the kidney make this a difficult process. This article outlines the available and developing options for such treatment. Nephron sparing surgery (NSS) is considered for selected cases of upper tract urothelial carcinoma (UTUC) as it maintains renal function and avoids morbidity associated with radical nephroureterectomy (RNU). The appropriate selection of patients suitable for NSS without compromising oncological outcomes can sometimes be difficult, given the limitations of diagnostic modalities. Recurrence rates for UTUC can be as high as 36 to 54% after NSS. Intraluminal adjuvant therapy can be attempted following NSS to reduce recurrence, but delivery to the upper tract is more challenging than into the bladder. Bacillus Calmette-Guerin (BCG) and chemotherapy such as Mitomycin (MMC) have been administered via nephrostomy or ureteric catheter, which requires invasive/repeated instrumentation of the upper urinary tract. Drug delivery by reflux from bladder instillation along indwelling stents has also been tried but can potentially be unreliable. Recently, a gel formulation of mitomycin has been developed for the controlled exposure of the upper urinary tract to treatment over a number of hours. Drug-eluting stents to deliver chemotherapy to the upper urinary tract have been developed but have not yet entered clinical practice. Endoluminal phototherapy utilising an intravenous photosensitising agent is another novel approach that has recently been described. Intraluminal therapies may be beneficial in decreasing recurrence rates in UTUC, but currently have some limitations in their usage. [ABSTRACT FROM AUTHOR]

The objective: to analyze the experience of using hyperthermic intravesical chemotherapy (HIVEC) with Mitomycin-C (MMC) and the addition of dimethyl sulfoxide (DMSO) in high-risk of non-muscle-invasive bladder cancer (HR NMIBC) patients and to compare oncological results with BCG therapy. Materials and methods. From March 2018 to January 2021, 53 patients with high-risk of NMIBC underwent a HIVEC adjuvant regimen at the University Clinic of Odessa National Medical University. The results were compared with a group of patients who received adjuvant intravesical BCG therapy from 2015 to 2019. In the HIVEC group, 16 (30.2%) patients with reduced bladder capacity underwent a session of the HIVEC therapy with prior injection of DMSO solution into the bladder. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were time to recurrence, progression-free survival (PFS), cancer-specific survival and overall survival at 36 months. Results. The incidence of the disease recurrence (42.6% vs 22.6%; p=0.028) and progression (20.4% vs 7.5%; p=0.50) were different between the BCG and HIVEC, respectively. The mean time to recurrence in patients who received HIVEC MMC was significantly higher than in patients of the BCG group: 31.5 months (95% CI: 29.1-34.0) versus 26.0 months (95% CI: 22.7-29.3), respectively (p=0.034). Cox regression analysis showed that the hazard ratio for HIVEC vs BCG for the RFS at 36 months was 0.48 (95% CI: 0.24-0.96; p=0.04). The RFS and the PFS indicators during the 36-month follow-up period in patients who received additional intravesical DMSO administration were not significantly different from other patients in the HIVEC therapy group. Conclusions. Hyperthermic intravesical chemotherapy with the addition of DMSO is a safe treatment option for patients with high-risk of noninvasive bladder cancer with efficacy comparable to BCG therapy. [ABSTRACT FROM AUTHOR]

The Escherichia coli Keio mutant collection has been a tool for assessing the role of specific genes and determining their role in E. coli physiology and uncovering novel functions. In this work, specific mutants in the DNA repair pathways and oxidative stress response were evaluated to identify the primary targets of silver nanoparticles (NPs) and their mechanism of action. The results presented in this work suggest that NPs mainly target DNA via double-strand breaks and base modifications since the recA, uvrC, mutL, and nfo mutants rendered the most susceptible phenotype, rather than involving the oxidative stress response. Concomitantly, during the establishment of the control conditions for each mutant, the katG and sodA mutants showed a hypersensitive phenotype to mitomycin C, an alkylating agent. Thus, we propose that KatG catalase plays a key role as a cellular chaperone, as reported previously for the filamentous fungus Neurospora crassa, a large subunit catalase. The Keio collection mutants may also be a key tool for assessing the resistance mechanism to metallic NPs by using their potential to identify novel pathways involved in the resistance to NPs. [ABSTRACT FROM AUTHOR]

Trabeculectomy is the main surgical treatment for glaucoma, but scar formation during wound healing may lead to surgical failure. In this study, we evaluated the efficacy of anti‐vascular endothelial growth factor (anti‐VEGF) and mitomycin C (MMC) on wound healing after glaucoma surgery. We have been looking for Pubmed, Embase and other databases. The last time we looked at an electronic database was August 2023. A case control study was conducted to compare the use of anti‐VEGF and mitomycin C for the treatment of glaucoma. We used the Cochrane standard methodology for collecting and analysing the data. Based on the criteria of inclusion, we have determined 369 related papers and selected seven eligible trials for data analysis. Three hundred and twenty‐six cases were treated with trabeculectomy, of which 166 were injected with anti‐VEGF and 160 were given MMC for trabeculectomy. In six trials, anti‐VEGF and MMC were not found to have any statistical significance on postoperative wound leakage after surgery (OR, 1.55; 95% CI, 0.71, 3.35 p = 0.27). The three trials showed that anti‐VEGF and MMC did not differ in terms of reducing postoperative wound hypotony after surgery (OR, 0.78; 95% CI, 0.20, 3.11 p = 0.73). Five trials demonstrated that anti‐VEGF and MMC were not associated with a lower incidence of shallow anterior chamber (OR, 1.17; 95% CI, 0.5, 2.76 p = 0.71). There is no significant difference in the effect of anti‐VEGF and MMC on wound healing after glaucoma surgery. A multicentre randomized controlled trial with a larger sample size is needed to confirm this study. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of aqueous and acetone extracts from Artemisia vulgaris L. (AV) and Artemisia alba Turra (AA), and two major polyphenols compounds (3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside) presented in both extracts of the plants against mitomycin C (MMC)-induced genomic instability. Genomic instability was measured using cytokinesis block micronucleus (MN) assay in human peripheral blood lymphocytes (PBLs) in vitro by analyzing two biomarkers – MN and nuclear division index (NDI). Extracts were tested in a concentration-dependent manner (10–250 µg/mL), while 3,5-dihydroxybenzoic acid and quercetin-3-O-glucopyranoside were tested in three different concentrations, in combination with 0.5 µg/mL of MMC. Aqueous and acetone extracts obtained from both plants significantly reduced MMC-induced MN frequency in PBLs, compared to positive control cells (p < 0.05). Extracts from AV did not affect NDI, whereas the concentrations of 10–100 μg/mL of aqueous and acetone AA extracts significantly elevated MMC-decreased NDI values in comparison to positive control cells (p < 0.05). Combined treatment of 3,5-dihydroxybenzoic acid and MMC showed a significant reduction of MMC-induced MN frequency, while quercetin-3-O-glucopyranoside increased MN frequency compared to positive control cells (p < 0.05). Both compounds decreased NDI values but only at the highest tested concentration of quercetin-3-O-glucopyranoside it was of greater significance. In conclusion, all extracts from AV and AA and 3,5-dihydroxybenzoic acid showed protective effect, whereby aqueous AA demonstrated the highest protective effect on MMC- induced genomic instability, while quercetin-3-O-glucopyranoside showed co-mutagen effect. [ABSTRACT FROM AUTHOR]

Objective: To examine the safety and efficacy of chemoablation using UGN-101 in patients with upper tract urothelial cancer (UTUC). Methods: We conducted a systematic search through 7 databases/registries to identify key observational and experimental studies reporting either the efficacy or safety of UGN-101 in UTUC patients regardless of the risk or grade of the disease. The outcomes included efficacy (complete/partial/no response, survival, death, recurrence, or progression) and safety endpoints. All meta-analyses were conducted through STATA. The prevalence rate and its 95% CI were pooled across studies. A subgroup meta-analysis was conducted on follow-up. The quality was assessed using the Newcastle Ottawa Scale. Twenty studies (1051 patients) were analyzed. Results: Complete response was reported in 49% (39%-60%) of cases, and 5% (0%-15%) had disease progression. Treatment cessation was reported in 13% (3%-27%) of patients. Four percent of cases needed radical nephroureterectomy. Recurrence and death occurred in 14% (7%-23%) and 6% (2%-10%) of patients. Complications occurred in 63% (39%-85%), the majority of which were of grades I, II, and III. Ureteral stenosis was the most common complication accounting for 35% of cases. Chemoablationrelated complications occurred more than procedure-related ones. Based on available evidence, the intracavitary instillation of UGN-101 gel provides an alternative therapeutic option for upper tract urothelial cancer. Conclusion: Chemoablation provides good clinical outcomes in terms of complete response, disease progression and recurrence, and the need to undergo nephroureterectomy. Complications were encountered in more than half the population; however, most of them were of low grades. [ABSTRACT FROM AUTHOR]

This study comprises the phytochemical characterization, the evaluation of the total phenolic content (TPC) and antioxidant activity (AA), and the investigation of the cyto-genotoxic and antigenotoxic potential of hydromethanolic extract derived from Salvia verticillata L. leaves. HPLC–DAD–ESI-MS and HPLC–DAD were used for the characterization of the extract and determination of the major ingredients. Afterwards, the TPC and AA were determined. The cytotoxic and genotoxic effect of the extract on cultured human lymphocytes at concentrations of 10, 25, and 50 μg mL−1 was investigated via the Cytokinesis Block MicroNucleus (CBMN) assay. Moreover, its antigenotoxic potential against the mutagenic agent mitomycin C (MMC) was assessed using the same assay. The hydromethanolic extract comprises numerous metabolites, with rosmarinic acid being the major compound. It had a high value of TPC and exerted significant AA as shown by the results of the Ferric Reducing Antioxidant Power (FRAP) and Radical Scavenging Activity by DPPH• assays. A dose-dependent cytotoxic potential was recorded, with the highest dose (50 μg mL−1) exhibiting statistically significant cytotoxicity. None of the tested concentrations induced significant micronuclei (MN) frequencies, indicating a lack of genotoxicity. All tested concentrations reduced the MMC-mediated genotoxic effects, with the two lowest showing statistically significant antigenotoxic potential. [ABSTRACT FROM AUTHOR]

Bladder cancer treatment with intravenous medication delivery has reasonable survival rates but modest therapeutic efficacy. Taking advantage of their superior diffusion and mixing capacities in urine compared to traditional pharmaceuticals or passive nanoparticles, self-propelled nanoparticles, also known as nanobots, have been proposed as a solution to the latter issue. Nonetheless, nothing is known about how well nanobots can translate into bladder cancer treatments. Here, urease-powered, radiolabelled mesoporous silica-based nanobots were evaluated in an orthotopic animal model of bladder cancer. Both in vivo and ex vivo findings showed increased accumulation of nanobots at the tumor location; positron emission tomography in vivo showed an eight-fold increase. The ex vivo tumor penetration by nanobots was validated by label-free optical contrast based on polarization-dependent scattered light-sheet microscopy of cleared bladders. Intravesically treatment was given to tumor-bearing mice. About 90% less tumor size was observed when radio-iodinated nanobots were used for radionuclide therapy, establishing nanobots as effective delivery nanosystems for bladder cancer treatment. [ABSTRACT FROM AUTHOR]

Increased intraocular pressure (IOP) is a risk factor for glaucoma. One treatment option is trabeculectomy. Antimetabolic agents are used in the operation to decrease the post‐operative scarring of the wound. The two most common medicines are Mitomycin C (MMC) and 5‐Fluorouracil (5‐FU). The aim of this research is to assess the effect of MMC on post‐operation wound healing in comparison with 5‐FU in addition to trabeculectomy. Well, we went through four common databases. Our language was limited to English during the study. The last time we looked at the e‐databases was August 2023. Case control studies were performed where MMC resulted in better wound healing than 5‐FU. Researchers selected a total of 1023 trials and eventually selected six trials for data analysis. Four hundred and ninety one cases of glaucoma were treated with trabeculectomy. Among them, 246 were given MMC and 245 were given 5‐FU during operation. Six trials showed that there was no statistical difference between MMC and 5‐FU in the incidence of post‐operative wound leak in glaucoma patients who received trabeculectomy (OR, 1.21; 95% CI, 0.63–2.30 p = 0.57); Five trials demonstrated that MMC was associated with a reduced risk of post‐operative corneal damage compared to 5‐FU injection (OR, 0.18; 95% CI, 0.06–0.56 p = 0.003); In both trials, the incidence of post‐operative bleeding was not significantly different from that of 5‐FU injected in the MMC group (OR, 0.33; 95% CI, 0.05–2.16 p = 0.25). Our results indicate that MMC is superior to 5‐FU in the reduction of post‐operative corneal injury. Additional comparisons between MMC and 5‐FU are required in order to increase the reliability and effectiveness of these findings. [ABSTRACT FROM AUTHOR]

Context.-- Noninvasive papillary urothelial carcinomas (PUCs) comprise most urinary bladder tumors. Distinction between low-grade (LG-PUC) and high-grade (HG-PUC) PUCs is pivotal for determining prognosis and subsequent treatment. Objective.-- To investigate the histologic characteristics of tumors with borderline features between LG-PUC and HG-PUC, focusing on the risk of recurrence and progression. Design.-- We reviewed the clinicopathologic parameters of noninvasive PUC. Tumors with borderline features were subcategorized as follows: tumors that look like LG-PUC but have occasional pleomorphic nuclei (1-BORD-NUP) or elevated mitotic count (2-BORD-MIT), and tumors with side-by-side distinct LG-PUC and less than 50% HG-PUC (3-BORD-MIXED). Recurrence-free, total progression-free, and specific invasion-free survival curves were derived from the Kaplan-Meier method, and Cox regression analysis was performed. Results.-- A total of 138 patients with noninvasive PUC were included, with the following distribution: LG-PUC (n = 52; 38%), HG-PUC (n = 34; 25%), BORD-NUP (n = 21; 15%), BORD-MIT (n = 14; 10%), and BORD-MIXED (n = 17; 12%). Median (interquartile range) follow-up was 44.2 months (29.9-73.1 months). Invasion-free survival was different between the 5 groups (P = .004), and pairwise comparison showed that HG-PUC had a worse prognosis compared with LG-PUC (P ≤ .001). On univariate Cox analysis, HG-PUC and BORD-NUP were 10.5 times (95% CI, 2.3-48.3; P = .003) and 5.9 times (95% CI, 1.1-31.9; P = .04) more likely to invade, respectively, when compared to LG-PUC. Conclusions.-- Our findings confirm a continuous spectrum of histologic changes in PUC. Approximately a third of noninvasive PUCs show borderline features between LG-PUC and HG-PUC. Compared with LG-PUC, BORD-NUP and HG-PUC were more likely to invade on follow-up. BORD-MIXED tumors did not statistically behave differently from LG-PUC. [ABSTRACT FROM AUTHOR]

Pulmonary veno-occlusive disease (PVOD), also known as “pulmonary arterial hypertension (PAH) with overt features of venous/capillary involvement”, is a rare cause of PAH characterised by substantial small pulmonary vein and capillary involvement, leading to increased pulmonary vascular resistance and right ventricular failure. Environmental risk factors have been associated with the development of PVOD, such as occupational exposure to organic solvents and chemotherapy, notably mitomycin. PVOD may also be associated with a mutation in the EIF2AK4 gene in heritable forms of disease. Distinguishing PVOD from PAH is critical for guiding appropriate management. Chest computed tomography typically displays interlobular septal thickening, ground-glass opacities and mediastinal lymphadenopathy. Life-threatening pulmonary oedema is a complication of pulmonary vasodilator therapy that can occur with any class of PAH drugs in PVOD. Early referral to a lung transplant centre is essential due to the poor response to therapy when compared with other forms of PAH. Histopathological analysis of lung explants reveals microvascular remodelling with typical fibrous veno-occlusive lesions. This review covers the main features distinguishing PVOD from PAH and two clinical cases that illustrate the challenges of PVOD management. [ABSTRACT FROM AUTHOR]

Aim: Our study aimed to establish a mouse model with colorectal cancer-induced peritoneal metastasis(PM) and to compare the efficacy of hyperthermic intraperitoneal chemotherapeutic agents, mitomycin C and oxaliplatin. Materials and Methods: The peritoneal metastasis model was established in nude mice using the CC531 colon carcinoma cell line. Models with PM were randomized into four groups of seven animals each: Group-1, control group; Group-2, hyperthermic intraperitoneal chemotherapy(HIPEC) with mitomycin C(MMC), and Group-3, HIPEC with Oxaliplatin(OXA). Results: Tumor development was achieved in all animals. While the tumor burden decreased significantly in the treatment Group-2(p=.013). In the PM mouse model, hyperthermic intraperitoneal administration of MMC had a higher tumoricidal effect than hyperthermic intraperitoneal administration of OXA. Conclusions: Our PM model provided a good opportunity to examine the efficacy of HIPEC and IPIP. Hyperethermic intraperitoneal mitomycin applied in the colorectal PM animal model was found to have higher tumoricidal activity than oxaliplatin. In future studies, we plan to evaluate efficacies of different drugs in the PM models we have created. [ABSTRACT FROM AUTHOR]

Purpose: Identify risk factors for biliary toxicity in patients with colorectal liver metastases who received floxuridine (FUDR) via a surgically implanted hepatic artery infusion pump (HAIP). Describe the incidence of biliary toxicity and evaluate relevant patterns in the biliary toxicity cohort. Methods: A single center, retrospective, case-control study included adult colorectal cancer patients with liver metastases who received at least one cycle of FUDR via a surgically implanted HAIP from 1 January 2017, to 1 October 2021. Patients were excluded if they had incomplete records, cholangiocarcinoma diagnosis, or received concurrent mitomycin and FUDR. Biliary toxicity criteria derived from existing HAIP literature were utilized to determine whether patients experienced biliary toxicity. Multiple variables were compared by univariate statistical analysis between the biliary toxicity and non-biliary toxicity cohorts to identify potential risk factors for development of FUDR-induced biliary toxicity. Results: Out of 50 patients who had a HAIP implanted, 39 met the inclusion criteria. Five of the 39 patients (12.7%) included in the analysis met the pre-specified biliary toxicity criteria. No risk factors for biliary toxicity were identified. All five patients who developed biliary toxicity demonstrated elevations in alkaline phosphatase (ALP) prior to meeting the toxicity criteria. Conclusion: Biliary toxicity remains a significant and therapy-limiting consequence of FUDR administration. Rising ALP may be an early indicator of subsequent biliary toxicity. Future studies with more patients may identify risk factors that can facilitate risk mitigation strategies. [ABSTRACT FROM AUTHOR]

The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The landscape of treatment for this cancer is rapidly evolving with novel combination strategies including immunotherapy, radiation therapy and biomarker-guided therapy. This review article features an overview of recent advancements in both locoregional and metastatic SCCA. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities. Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line chemoradiotherapy (CRT), and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments and novel agents. Another critical aspect of current research in SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) and circulating tumor DNA. [ABSTRACT FROM AUTHOR]

Simple Summary: This comprehensive review discusses the current status and future prospects of intravesical therapy for upper urinary tract urothelial carcinoma (UTUC). It emphasizes the need to understand its role in UTUC management and the importance of personalized strategies for drug selection, dosage, timing and frequency to optimize treatment outcomes and reduce intravesical recurrence. By summarizing historical development, clinical trials, guideline recommendations, and clinical applications, this review provides valuable insights. We aim to guide future studies and impact the research in UTUC, advancing the understanding and utilization of intravesical therapy for UTUC. Upper tract urothelial carcinoma (UTUC) poses unique challenges in diagnosis and treatment. This comprehensive review focuses on prophylactic intravesical therapy for UTUC, summarizing key aspects of intravesical therapy in various clinical scenarios, including concurrent with or following radical nephroureterectomy, kidney-sparing surgery, ureteroscopy-guided biopsy. The incidence of intravesical recurrence in UTUC after surgical treatment is significant, necessitating effective preventive measures. Intravesical therapy plays a vital role in reducing the risk of bladder recurrence following UTUC surgery. Tailoring timing, drug selection, dosage, and frequency is vital in optimizing treatment outcomes and reducing intravesical recurrence risk in UTUC. This review provides a comprehensive summary of the history, clinical trials, guideline recommendations, and clinical applications of intravesical therapy for UTUC. It also discusses the future directions based on current clinical needs and ongoing trials. Future directions entail optimizing dosage, treatment duration, and drug selection, as well as exploring novel agents and combination therapies. Intravesical therapy holds tremendous potential in improving outcomes for UTUC patients and reducing the risk of bladder recurrence. Although advancements have been made in UTUC treatment research, further refinements are necessary to enhance efficacy and safety. [ABSTRACT FROM AUTHOR]

Selenium nanoparticles (SeNPs) are worthy of attention and development for nutritional supplementation due to their health benefits in both animals and humans with low toxicity, improved bioavailability, and controlled release, being greater than the Se inorganic and organic forms. Our previous study reported that Anoectochilus burmannicus extract (ABE)-synthesized SeNPs (ABE-SeNPs) exerted antioxidant and anti-inflammatory activities. Furthermore, ABE could stabilize and preserve the biological activities of SeNPs. To promote the ABE-SeNPs as supplementary and functional foods, it was necessary to carry out a safety assessment. Cytotoxicity testing showed that SeNPs and ABE-SeNPs were harmless with no killing effect on Caco2 (intestinal epithelial cells), MRC-5 (lung fibroblasts), HEK293 (kidney cells), LX-2 (hepatic stellate cells), and 3T3-L1 (adipocytes), and were not toxic to isolated human PBMCs and RBCs. Genotoxicity assessments found that SeNPs and ABE-SeNPs did not induce mutations in Salmonella typhimurium TA98 and TA100 (Ames test) as well as in Drosophila melanogaster (somatic mutation and recombination test). Noticeably, ABE-SeNPs inhibited mutation in TA98 and TA100 induced by AF-2, and in Drosophila induced by urethane, ethyl methanesulfonate, and mitomycin c, suggesting their anti-mutagenicity ability. This study provides data that support the safety and anti-genotoxicity properties of ABE-SeNPs for the further development of SeNPs-based food supplements. [ABSTRACT FROM AUTHOR]

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of intralesional mitomycin C versus triamcinolone in reducing the recurrence of urethral stricture after internal optical urethrotomy. Materials and Methods: This randomized control trial was conducted at Institute of Kidney Diseases, Hayatabad Medical Complex Peshawar from January 2016 to January 2017. We enrolled 134 patients fulfilling the inclusion criteria. Urine R/E, blood investigation followed by x-ray KUB, ultrasound of the pelvis and abdomen once done with it then will proceed to retrograde urethrogram supplemented by Uroflometry & Flexible urethroscopy. Patient were regularly followed up on 3month interval for 1 year once the Mitomycin or triamcinolone injected intralesionally with TLA needle using straight working channel Pediatric cystoscope at 12, 3 & 9 o'clock positions. On each follow up uroflowmetry, & if needed Retrograde Urethrogram (R.U.G) was performed. On last follow up R.U.G was mandatory to rule out stricture. Results: Total 134 patients were enrolled in the study divided in to two groups Group A (Intralesinal Mitomycin) and Group B (Triamcinolone) after internal optical urethrotomy. Mean and SD of age for Group A was recorded as 47.4+14.2 and Group B was recorded as 46.58+14.27. Overall, only 29 (21.64%) patients demonstrated recurrence, whereas in the remaining 105 (78.35%) patients no recurrence of urethral stricture post procedure was documented on follow up. In Group A the recurrence was recorded as 9 (6.71%) whereas 58 (43.28%) patients had no recurrence. In Group B 20 (14.92%) patients had recurrence whereas 47 (35.07%) patients had no recurrence. P Value= 0.021. Frequency and percentage for stricture site between the two groups were recorded as 32 (23.88%) in Bulbar, 27 (20.14%) in Penile and 8 (5.79%) both Bulbar and Penile in Group A and in Group B 35 (26.11%) were recorded in Penile, 21 (15.67%) in Bulbar and 11 (8.20%) in both sites. Conclusion: Mitomycin C was found to be highly effective in preventing the recurrence of urethral stricture after IOU in comparison with triamcinolone. [ABSTRACT FROM AUTHOR]

The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel. [ABSTRACT FROM AUTHOR]

Trabeculectomy (TB) with mitomycin C (MMC) is a mainstay of glaucoma surgery for intraocular pressure reduction and visual field preservation, but surgical outcomes are often limited by episcleral and subconjunctival fibrosis leading to intraocular pressure (IOP) spikes. Retrospective case series presents seven eyes at a tertiary glaucoma center where open bleb needling was performed in combination with a collagen matrix implant and MMC following failed TB due to excessive fibrosis. Seven eyes of seven patients were included. Baseline IOP was 23.9 (±7.4) mmHg with a significant decrease on post-operative (post-op) day 1 to 4.6 mmHg. By post-op month 1, all eyes maintained a non-hypotonus IOP ≥ 5. Notably, four eyes (57%) had at least 1 unsuccessful open bleb needling without a collagen matrix implant prior. All eyes were complication-free by the latest visit without any complication-related visual decline, and six eyes (86%) were glaucoma medication-free at the most-recent post-op follow-up (12.4 ± 11.4 months). All cases were performed by one experienced glaucoma subspecialist (author DL). Open bleb needling and MMC in combination with a collagen matrix implant may result in improved and sustained IOP control for encapsulated blebs following failed trabeculectomy, especially in those with prior unsuccessful bleb revisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Upper tract urothelial carcinoma (UTUC) is a lethal cancer of the urinary tract. Radical nephroureterectomy with bladder cuff excision is the gold standard for the management of patients with UTUC. Nevertheless, less-invasive surgeries to preserve maximum kidney function, such as endoscopic ablation and segmental ureteral resection, have become the preferred options in select patients. In this paper, we reviewed the latest evidence on the kidney-sparing management of upper tract urothelial carcinoma. We showed that these approaches are acceptable for low- as well as select high-risk patients who are not eligible for radical treatments. The main advantages of such approaches include renal function preservation as well as decreased surgical morbidity associated with radical treatments. Purpose: To review the latest evidence on the modern techniques and outcomes of kidney-sparing surgeries (KSS) in patients with upper tract urothelial carcinoma (UTUC). Methods: A comprehensive literature search on the study topic was conducted before 30 April 2023 using electronic databases including PubMed, MEDLINE, and EMBASE. A narrative overview of the literature was then provided based on the extracted data and a qualitative synthesis of the findings. Results: KSS is recommended for low- as well as select high-risk UTUCs who are not eligible for radical treatments. Endoscopic ablation is a KSS option that is associated with similar oncological outcomes compared with radical treatments while preserving renal function in well-selected patients. The other option in this setting is distal ureterectomy, which has the advantage of providing a definitive pathological stage and grade. Data from retrospective studies support the superiority of this approach over radical treatment with similar oncological outcomes, albeit in select cases. Novel chemoablation agents have also been studied in the past few years, of which mitomycin gel has received FDA approval for use in low-risk UTUCs. Conclusion: KSSs are acceptable approaches for patients with low- and select high-risk UTUCs, which preserve renal function without compromising the oncological outcomes. [ABSTRACT FROM AUTHOR]

Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine. • Grade 2+ acute toxicity was common and similar for 32- and 20-fraction radiotherapy. • Observed grade 3+ acute toxicity in RAIDER was lower than reported in previous trials. • Acute toxicity following bladder radiotherapy returns to baseline levels by 3 months. • The acute toxicity profile varied by concomitant radiosensitising treatment. • Bowel (but not urinary) toxicity appears higher in those receiving gemcitabine. [ABSTRACT FROM AUTHOR]

The treatment of implant‐associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic‐tolerant persister cells. This need is addressed herein through an engineering of antibody‐drug conjugates (ADCs) that contain an anti‐neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non‐specific counterpart, in suspension and within biofilms, in vitro, and in an implant‐associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms. [ABSTRACT FROM AUTHOR]

Radioresistant microorganisms possess inimitable capabilities enabling them to thrive under extreme radiation. However, the existence of radiosensitive microorganisms inhabiting such an inhospitable environment is still a mystery. The current study examines the potential of radioresistant microorganisms to protect radiosensitive microorganisms in harsh environments. Bacillus subtilis strain ASM-1 was isolated from the Thal desert in Pakistan and evaluated for antioxidative and radioprotective potential after being exposed to UV radiation. The strain exhibited 54.91% survivability under UVB radiation (5.424 × 103 J/m2 for 8 min) and 50.94% to mitomycin-C (4 µg/mL). Extracellular fractions collected from ASM-1 extracts showed significant antioxidant potential, and chemical profiling revealed a pool of bioactive compounds, including pyrrolopyrazines, amides, alcoholics, and phenolics. The E-2 fraction showed the maximum antioxidant potential via DPPH assay (75%), and H2O2 scavenging assay (68%). A combination of ASM-1 supernatant with E-2 fraction (50 µL in a ratio of 2:1) provided substantial protection to radiosensitive cell types, Bacillus altitudinis ASM-9 (MT722073) and E. coli (ATCC 10536), under UVB radiation. Docking studies reveal that the compound supported by literature against the target proteins have strong binding affinities which further inferred its medical uses in health care treatment. This is followed by molecular dynamic simulations where it was observed among trajectories that there were no significant changes in major secondary structure elements, despite the presence of naturally flexible loops. This behavior can be interpreted as a strategy to enhance intermolecular conformational stability as the simulation progresses. Thus, our study concludes that Bacillus subtilis ASM-1 protects radiosensitive strains from radiation-induced injuries via biofilm formation and secretion of antioxidative and radioprotective compounds in the environment. [ABSTRACT FROM AUTHOR]

By exploiting the combined use of a heterogeneous recyclable palladium(II)-bis(N-heterocyclic carbene) catalyst and cyclopentyl methyl ether (CPME) as a convenient recoverable safer reaction medium, an effective wasteminimized approach has been developed for the intramolecular Pd-catalyzed C(sp3)-H activation of methyl pyrrole derivatives. This synthetic tools has allowed to access condensed N-heterocycles generally endowed with biological activities and representatively are the core motif of complex molecules such as Mitomycines and Tylophorines. The heterogeneous catalytic system could be recovered and reused up to representative five runs without any loss in efficiency. The target products (19 examples) have been obtained selectively and with excellent isolated yields up to 93%. The approach leads to the definition of a protocol with a very good E-factor (21) which is much lower (up to 98%) than those of comparable literature examples. Other green metrics have been calculated and the data collected demonstrate that our newly developed protocol is very promising in terms of its environmental impact profile. [ABSTRACT FROM AUTHOR]

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10–15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5–68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17–92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC. [ABSTRACT FROM AUTHOR]

Anamnesis: A descriptive series of six cases of dogs with glaucoma are presented comparing the fibrosis inhibition effect of three drugs used during trabeculectomy (TEC). Clinical findings: The patients were diagnosed with primary chronic closedangle glaucoma refractory to topical medical treatment with no pupillary light reflex and negative eyeblink response to threat and ocular pain. Therapeutic approach: Two patients received an intraoperative application of bevacizumab; two received 5-fluorouracil; and two, mitomycin C. Intraocular pressure (IOP) and filtering ampoule were observed on days 1, 7, 30, 60, and 90 post-surgery. Results and conclusion: Bevacizumab regulated IOP under 25 mmHg, constituting the drug of choice for dogs with primary closed-angle glaucoma without previous positive response to topical therapy and subjected to TEC, when compared with 5-fluorouracil and MMC regarding the inhibitory effect of fibrosis. [ABSTRACT FROM AUTHOR]

Background: Kasai portoenterostomy (KPE) is the initial treatment for biliary atresia (BA). Even after initial jaundice clearance, a significant number of children presented with the reappearance of symptoms due to ongoing fibrosis involving porta and intrahepatic ducts. Mitomycin-C (MMC) is an antifibrotic agent, and the study hypothesized that local application of MMC at porta can decrease fibrosis, which can improve jaundice clearance and lead to better native liver survival (NLS). Materials and Methods: This prospective randomized control trial included children with BA, who were allocated to groups A or B. The patients in both groups underwent standard KPE; in addition, a 5 French infant feeding tube (IFT) was placed near the porta through the Roux limb in Group B children. During the postoperative period, MMC was locally instilled over the porta in Group B children through IFT. Postoperative jaundice clearance and NLS were assessed and compared. Results: A total of 27 children were enrolled in the study, 16 in Group A and 11 in Group B. Both groups were comparable preoperatively. Although the NLS was not statistically significant in Group B, the survival was quite higher, that was 91%, 81%, and 73% at 6 months, 1 year, and 2 years, respectively, compared to 63%, 50%, and 38% in Group A. Conclusion: Children in Group B clinically showed an early jaundice clearance and a better trend of serial bilirubin levels as well as longer NLS than Group A, but it was not statistically significant. The procedure was technically easy, and no complication was encountered related to surgical technique or MMC instillation. [ABSTRACT FROM AUTHOR]

Isolated from Streptomyces caespitosus, mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It has been employed in pterygium surgery, ocular surface neoplasia, and refractive surgery. Currently, there is no definite consensus on the treatment protocols for each of the aforementioned applications. Although its benefits in the management of corneal and external diseases are promising, MMC use has potential complications including endothelial cell loss, corneal perforation, scleral melt, secondary glaucoma, iritis, and endophthalmitis. This article will review the literature regarding the use of MMC in the field of cornea and external disease and describe protocols employed with corresponding outcomes. [ABSTRACT FROM AUTHOR]

Tumor protein 53 (TP53) mutation in bladder carcinoma (BC), upregulates the transcription of carbamoyl phosphate synthetase 1 (CPS1), to reduce intracellular ammonia toxicity. To leverage ammonia combating BC, here, an intravesically perfusable nanoporter‐encased hydrogel system is reported. A biomimetic fusogenic liposomalized nanoporter (FLNP) that is decorated with urea transporter‐B (UT‐B) is first synthesized with protonated chitosan oligosaccharide for bladder tumor‐targeted co‐delivery of urease and small interfering RNA targeting CPS1 (siCPS1). Mussel‐inspired hydrogel featured with dual functions of bio‐adhesion and injectability is then fabricated as the reservoir for intravesical immobilization of FLNP. It is found that FLNP‐mediated UT‐B immobilization dramatically induces urea transportation into tumor cells, and co‐delivery of urease and siCPS1 significantly boosts ammonia accumulation in tumor inducing cell apoptosis. Treatment with hybrid system exhibits superior anti‐tumor effect in orthotopic bladder tumor mouse model and patient‐derived xenograft model, respectively. Combined with high‐protein diet, the production of urinary urea increases, leading to an augmented intracellular deposition of ammonia in BC cells, and ultimately an enhanced tumor inhibition. Together, the work establishes that cascade modulation of ammonia in tumor cells could induce tumor apoptosis and may be a practical strategy for eradication of TP53‐mutated bladder cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most prevalent malignancies in the urinary system, including non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). Radical cystectomy combined with systemic chemotherapy remains the standard treatment for MIBC. However, serious undesired side effects and drug resistance of chemotherapy have hampered its wide application. Here, we facilely fabricated a pH-responsive RGD- and MoS2-conjugated hydroxyethyl starch-doxorubicin (HES-DOX-RGD/MoS2). The prodrug could self-assemble into nanoscopic micelle with a radius of ~ 56 nm in the aqueous environment and was stable in the physiological environment. The targeted HES-DOX-RGD/MoS2 showed a significant in vitro antiproliferative capability toward bladder cancer cells through the chemotherapy combined with photothermal therapy. Hence, we had reasons to believe that targeted HES-DOX-RGD/MoS2 had great potential to treat bladder cancer in the future. [ABSTRACT FROM AUTHOR]

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-y, TGF-/1, and TNF-a. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) dueto its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure. [ABSTRACT FROM AUTHOR]

Objective: To study the role of MLN4924 in corneal stem cell maintenance and corneal injury repair. Methods: In cell experiments, the Sprague–Dawley (SD) rat corneal epithelial cells were co-cultured with mitomycin C-inactivated mouse feeder cells in a supplemental hormonal epithelial medium (SHEM) with or without MLN4924. Cells were photographed using an optical microscope. Furthermore, we performed crystal violet, polymerase chain reaction (PCR), and immunofluorescence staining on limbal stem cells (LSCs). In animal experiments, we scraped the corneal epithelium with a central corneal diameter of 4 mm in SD rats. The area of the corneal epithelial defect was calculated by fluorescein sodium staining. Results: LSCs in the MLN4924 group had significantly proliferated. The MLN4924 treatment evidently enhanced the clone formation rate and clone area of LSCs. The expression levels of Ki67, p63, ABCG2, Bmi1, and C/EBPδ increased in LSCs after MLN4924 treatment, whereas the expression of K12 decreased. At 12 and 24 h after scraping, the corneal epithelium recovery rate in the eyes of the MLN4924-treated rats was accelerated. Conclusions: MLN4924 can maintain stemness, reduce differentiation, promote the proliferative capacity of rat LSCs, and accelerate corneal epithelial wound healing in SD rats. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat's ocular injury. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the incidence of postoperative ptosis after primary trabeculectomy and the possible factors contributing to ptosis. Materials and Methods: A total of 312 patients (339 eyes) who underwent trabeculectomy with mitomycin-C between 2015 and 2020 were retrospectively evaluated. Patients who had regular follow-up for at least 6 months and no history of ptosis or ptosis surgery were included. Age, sex, glaucoma type, preoperative and postoperative intraocular pressure, preoperative and postoperative antiglaucoma medications, number of antiglaucoma drops, duration of antiglaucoma medication use, history of eye itching due to antiglaucoma medication-associated allergy, duration of follow-up, postoperative needling, needling time, and ocular massage were recorded. Ptosis was defined as >2 mm reduction in margin-reflex distance 1 from preoperative levels. Ptosis that had not improved for at least 6 months was considered persistent ptosis. Multivariate logistic regression was used to determine potential predictors of ptosis development. Results: Ptosis after trabeculectomy was observed in 35 of 339 eyes (10.3%). Thirty eyes of 30 patients (8.8%) had transient ptosis and 5 eyes of 4 patients (1.5%) had persistent ptosis. Preoperative duration of antiglaucoma medication use, drug(s) used (prostaglandin analogs, beta-blockers, alpha-2 agonists, carbonic anhydrase inhibitors, or combinations of these), needling time, and ocular massage after trabeculectomy did not differ significantly between groups (p>0.05). Needling and eye itching due to antiglaucoma medication-associated allergy were significantly higher in patients with ptosis (p<0.05). Conclusion: Ptosis after trabeculectomy is an important problem for glaucoma patients. It has been observed that needling and a history of eye itching due to antiglaucoma drug-associated allergy may increase the risk of ptosis. [ABSTRACT FROM AUTHOR]

The transformation of nonmuscle‐invasive bladder cancer (BLCa) to muscle‐invasive type and distant metastasis are the two major threats to patients after surgery. Thus, it is important to identify the key genes of BLCa cell invasion and metastasis. Long noncoding RNA (lncRNA) is a potential clinical tool for cancer diagnosis and treatment. Herein, we verified that lncRNA SNHG3 is upregulated in human BLCa specimens and is proportional to poor clinical prognosis via a combination of bioinformatic analyses and wet bench experiments. Then, we constructed SNHG3 knockdown and overexpression cell models via lentiviral packaging and CRISPR‐Cas9 technique. Fluorescence in situ hybridization assay showed that SNHG3 is distributed in both the nucleus and cytoplasm of BLCa cell lines. In vitro assays including CCK‐8, EdU, colony formation, wound healing, transwell, and tube formation demonstrated that SNHG3 knockdown and overexpression potently inhibited and enhanced BLCa cell proliferation, migration, invasion, and angiogenesis. In addition, IVIS imaging revealed that SNHG3 knockdown could significantly inhibit M‐NSG mice xenograft tumor growth. Next, RNA sequencing, bioinformatics analyses and western blots indicated that SNHG3 could promote c‐MYC expression. RNA immunoprecipitation, actinomycin D assay and western blot assays suggested that SNHG3 could also bind c‐MYC protein which subsequently facilitate the stabilization of BMI1 mRNA, thus enhancing BMI1 protein level. However, SNHG3 knockdown had a slightly weaker inhibitory effect on BMI1 expression than c‐MYC knockdown. Further, in vitro assays demonstrated that BMI1 knockdown could suppress the SNHG3 activation‐induced tumor promoting effect in BLCa cells. Overall, this study has provided new insights into the potential implication of lncRNA SNHG3 in the pathogenesis of BLCa. Importantly, SNHG3/c‐MYC/BMI1 axis may be a novel target for regulating tumor growth and metastasis in BLCa patients. [ABSTRACT FROM AUTHOR]

Background: The inhibition of ubiquitin-specific proteases (USPs) is a novel and promising direction in the development of molecularly targeted therapies in oncology. The aim of the present study was to examine whether Degrasyn could be a potential therapeutic agent against bladder cancer (BC). Also, we aimed to determine whether Degrasyn is more effective in terms of anti-cancer activity compared to the non-selective DUB inhibitor PR-619. To facilitate the translational value of the obtained results, our experiments were performed using both human and canine in vitro models of BC. Methods: Human T24 (urothelial grade III BC) and SV-HUC-1 (non-tumorigenic urothelial cell line), as well as canine K9TCC-PU-NK and RDSVS-TCC1 (both derived from invasive grade III urothelial bladder tumors) cell lines, were used in the present study. Cell proliferation was determined using the MTT assay and Ki-67 proliferation assay, and the level of apoptosis induced by Degrasyn and PR-619 was evaluated by Annexin V-FITC staining and caspase 3/7 activation assay. Western blot was used to assess DNA damage and key proteins involved in apoptosis. Results: Degrasyn inhibited the proliferation of all BC cell lines in a concentration- and time-dependent manner. Lower concentrations of Degrasyn were more potent against human and canine BC cell lines compared to PR-619. Degrasyn induced caspase-dependent apoptosis and triggered DNA damage. PR-619 did not show a significant pro-apoptotic effect. Conclusions: Our results demonstrate that Degrasyn significantly impairs the growth of in vitro models of human and canine BC. Selective USP inhibition with Degrasyn seems to be more effective in reducing BC cell proliferation and inducing apoptosis and DNA damage than non-selective USP inhibition with PR-619. [ABSTRACT FROM AUTHOR]

The Rho/ROCK pathway regulates diverse cellular processes and contributes to the development and advancement of several types of human cancers. This study investigated the role of specific Rho GTPase-activating proteins (RhoGAP), ARHGAP6, in bladder cancer (BC). In this study, ARHGAP6 expression in BC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism ARHGAP6 of in BC. The mRNA and protein levels of ARHGAP6 significantly reduced in human BC tissues and cell lines compared with corresponding adjacent non-cancerous tissues and normal urothelial cells. In vitro, ARHGAP6 overexpression markedly decreased the viability, migration, and invasion of BC cells. Interestingly, low ARHGAP6 expression in BC strongly correlated with poor patient survival and was highly associated with metastasis and β-catenin signaling. Furthermore, ARHGAP6 expression strongly influenced the sensitivity of BC cells to mitomycin C treatment. Together, our results demonstrate that ARHGAP6 plays critical roles in regulating the proliferation, migration, invasion, and metastasis of BC cells possibly via the modulation of β-catenin and strongly influences the chemosensitivity of BC cells. [ABSTRACT FROM AUTHOR]