Design and Validation of a Novel 3D-Printed Retrograde Intrarenal Surgery Trainer.

OBJECTIVE: To report on the design of a novel 3D-printed retrograde intrarenal surgery (RIRS) benchtop trainer and detail its validation against real-life experiences. METHODS: Digital Imaging and Communications in Medicine (DICOM) files of 2 patients with normal computed tomography of the kidney and bladder were converted into stereolithography files to create 3D triangular mesh models. These images were further refined using Autodesk Meshmixer. These 3D models were fabricated through additive manufacturing, a process commonly known as 3D printing, and assembled in a polypropylene case. After development, the model was validated by 40 experienced urologists and urology residents in their final year of training. They were asked to rate the components of the simulation using a 9-point questionnaire. RESULTS: The model's value in understanding the principles of RIRS and simulating contextual anatomy had mean scores of 9.43 (standard deviation [SD] = 0.74) and 9.21 (SD = 1.03), respectively. Mean scores for specific steps in RIRS were 8.07 (SD 1.47) for cannulating the ureteric orifice, 8.61 (SD 1.24) for inserting the ureteric access sheath, 9.29 (SD 0.97) for performing a renoscopy and evaluating all the calyces, 9.46 (SD 0.87) for laser lithotripsy, and 9.17 (SD 0.94) for manual stone retrieval. Participants scored the model with a mean score of 9.04 (SD 0.87) regarding realism and a mean score of 9.18 (SD 0.89) when evaluating its ability to enhance a trainee's confidence in RIRS. CONCLUSION: The model performed well for all components of RIRS. This model allows high fidelity of the simulation and is cost-effective, portable, durable, reusable, and compatible with standard ureteroscopes.

Statistical Analysis of Factors Associated with Diarrhea in Yemeni Children under Five: Insights from the 2022-2023 Multiple Indicator Cluster Survey.

Diarrheal disease remains a significant cause of preventable morbidity and mortality in the pediatric population, particularly among children below five years of age. Although the occurrence of diarrheal episodes is on the decline, its impact continues to escalate at a concerning rate among children under the age of five, especially in developing countries. The objective of this paper is to investigate the factors associated with diarrhea in Yemeni children younger than five years, drawing on data from the latest edition of the Multiple Indicator Cluster Survey (MICS) Yemen conducted in 2022-2023. To identify factors associated with the prevalence of childhood diarrhea, bivariate analysis and multivariable logistic regression were utilized. The findings of this study suggest that age group 6-23, unimproved sanitation, and low-income households are associated with high risk of diarrhea in children under five years of age in Yemen. The study contributes additional evidence regarding factors that should be prioritized in public health strategies geared towards reducing diarrheal prevalence among Yemeni children.

Catalytically distinct IDH1 mutants tune phenotype severity in tumor models.

Mutations in isocitrate dehydrogenase 1 (IDH1) impart a neomorphic reaction that produces the oncometabolite D-2-hydroxyglutarate (D2HG), which can inhibit DNA and histone demethylases to drive tumorigenesis via epigenetic changes. Though heterozygous point mutations in patients primarily affect residue R132, there are myriad D2HG-producing mutants that display unique catalytic efficiency of D2HG production. Here, we show that catalytic efficiency of D2HG production is greater in IDH1 R132Q than R132H mutants, and expression of IDH1 R132Q in cellular and mouse xenograft models leads to higher D2HG concentrations in cells, tumors, and sera compared to R132H-expressing models. Reduced representation bisulfite sequencing (RRBS) analysis of xenograft tumors shows expression of IDH1 R132Q relative to R132H leads to hypermethylation patterns in pathways associated with DNA damage. Transcriptome analysis indicates that the IDH1 R132Q mutation has a more aggressive pro-tumor phenotype, with members of EGFR, Wnt, and PI3K signaling pathways differentially expressed, perhaps through non-epigenetic routes. Together, these data suggest that the catalytic efficiency of IDH1 mutants modulate D2HG levels in cellular and in vivo models, resulting in unique epigenetic and transcriptomic consequences where higher D2HG levels appear to be associated with more aggressive tumors.

Utilization of barley and parsley for the management of urolithiasis among the Saudi Arabian population.

Objective: To determine the utilization of barley and parsley for managing urolithiasis among the Saudi Arabian population. Methods: This is a prospective cross-sectional survey-based study. The survey comprised questions about the use of barley, parsley, and other therapies for managing urolithiasis. A WhatsApp® message with the link to the study survey was sent out to family, friends, patients, and other acquaintances residing in the Kingdom of Saudi Arabia (KSA). Results: A total of 1014 respondents completed the survey, of which 44.8% indicated that they utilized barley, 38.3% stated that they used parsley, and 4.2% indicated that they utilized other non-medical remedies to treat or prevent kidney stones. In contrast, only 29.5% stated that they utilized potassium citrate and/or magnesium citrate, and only 14.4% indicated that they consumed greater amounts of water to treat or prevent kidney stones. Conclusion: Our study findings indicate that among the Saudi Arabian population, non-conventional therapies such as barley and parsley are more commonly utilized for managing urolithiasis rather than established therapies such as increasing water intake and the use of potassium-citrate/ magnesium-citrate. There is a need to conduct large-scale clinical studies to evaluate the efficacy and safety of barley, parsley, and other non-conventional therapies for treating urolithiasis.

Pathological response in resectable non-small cell lung cancer: a systematic literature review and meta-analysis.

BACKGROUND: Surrogate endpoints for overall survival in patients with resectable non-small cell lung cancer receiving neoadjuvant therapy are needed to provide earlier treatment outcome indicators and accelerate drug approval. This study's main objectives were to investigate the association among pathological complete response, major pathological response, event-free survival and overall survival and to determine whether treatment effects on pathological complete response and event-free survival correlate with treatment effects on overall survival. METHODS: A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable non-small cell lung cancer. Analysis at the patient level using frequentist and Bayesian random effects (hazard ratio [HR] for overall survival or event-free survival by pathological complete response or major pathological response status, yes vs no) and at the trial level using weighted least squares regressions (hazard ratio for overall survival or event-free survival vs pathological complete response, by treatment arm) were performed. RESULTS: In both meta-analyses, pathological complete response yielded favorable overall survival compared with no pathological complete response (frequentist, 20 studies and 6530 patients: HR = 0.49, 95% confidence interval = 0.42 to 0.57; Bayesian, 19 studies and 5988 patients: HR = 0.48, 95% probability interval = 0.43 to 0.55) and similarly for major pathological response (frequentist, 12 studies and 1193 patients: HR = 0.36, 95% confidence interval = 0.29 to 0.44; Bayesian, 11 studies and 1018 patients: HR = 0.33, 95% probability interval = 0.26 to 0.42). Across subgroups, estimates consistently showed better overall survival or event-free survival in pathological complete response or major pathological response compared with no pathological complete response or no major pathological response. Trial-level analyses showed a moderate to strong correlation between event-free survival and overall survival hazard ratios (R2 = 0.7159) but did not show a correlation between treatment effects on pathological complete response and overall survival or event-free survival. CONCLUSION: There was a strong and consistent association between pathological response and survival and a moderate to strong correlation between event-free survival and overall survival following neoadjuvant therapy for patients with resectable non-small cell lung cancer.

Lack of consensus in atypical congenital obstructive urethral lesions in children: Snapshot of the web-based ObsCUre (obstruction to the child urethra) study.

Background: Atypical Congenital Obstructive Urethral Lesions (ACOUL) are uncommon causes of urethral obstruction in children. They include Cobb's collar or Moorman's ring, Type III posterior urethral valve (PUV), congenital urethral narrowing and anterior urethral valves. This study is aimed to evaluate the knowledge and current practice amongst clinicians attending to ACOUL. An international online case based questionnaire was performed. Materials and methods: A survey was administered to members of international urological societies. It included 22 clinical questions on cases with ACOUL (14 questions suitable for statistical analysis) using cases of Type I PUV as controls. Two sets of paired questions evaluated change in opinion(s) after additional information was provided. Results: One hundred twenty-one participants responded with 71% reporting exposure of less than 5 cases per annum. In questions regarding diagnosis between 11.6% (14/121) and 21.5% (26/121) of participants identified the ACOUL as PUV. Among them, 66% of respondents agreed on ACOUL's causative role in urethral obstruction. Gini coefficient was consistently lower for ACOUL compared to PUV: diagnosis (mean 0.33 vs. 0.44) and prognosis (0.23 vs. 0.43). High intra-rater concordance (kappa 0.420.57) was observed for paired questions-a mean of 5.79% (7.44% and 4.13% for questions 10 and 12, 16 and 17, respectively) of participants changed their answers from an alternate diagnosis to the correct diagnosis of ACOUL after viewing endoscopic images. High variation in management of ACOUL was noted (Gini 0.51). Conclusions: This global snapshot survey identified substantial inconsistency among clinicians dealing with ACOUL. Although rarely encountered in clinical practice, better overall education of ACOUL is warranted.

Elucidating the molecular basis of ATP-induced cell death in breast cancer: Construction of a robust prognostic model.

BACKGROUND: Breast cancer is a multifaceted and formidable disease with profound public health implications. Cell demise mechanisms play a pivotal role in breast cancer pathogenesis, with ATP-triggered cell death attracting mounting interest for its unique specificity and potential therapeutic pertinence. AIM: To investigate the impact of ATP-induced cell death (AICD) on breast cancer, enhancing our understanding of its mechanism. METHODS: The foundational genes orchestrating AICD mechanisms were extracted from the literature, underpinning the establishment of a prognostic model. Simultaneously, a microRNA (miRNA) prognostic model was constructed that mirrored the gene-based prognostic model. Distinctions between high- and low-risk cohorts within mRNA and miRNA characteristic models were scrutinized, with the aim of delineating common influence mechanisms, substantiated through enrichment analysis and immune infiltration assessment. RESULTS: The mRNA prognostic model in this study encompassed four specific mRNAs: P2X purinoceptor 4, pannexin 1, caspase 7, and cyclin 2. The miRNA prognostic model integrated four pivotal miRNAs: hsa-miR-615-3p, hsa-miR-519b-3p, hsa-miR-342-3p, and hsa-miR-324-3p. B cells, CD4+ T cells, CD8+ T cells, endothelial cells, and macrophages exhibited inverse correlations with risk scores across all breast cancer subtypes. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis revealed that genes differentially expressed in response to mRNA risk scores significantly enriched 25 signaling pathways, while miRNA risk scores significantly enriched 29 signaling pathways, with 16 pathways being jointly enriched. CONCLUSION: Of paramount significance, distinct mRNA and miRNA signature models were devised tailored to AICD, both potentially autonomous prognostic factors. This study's elucidation of the molecular underpinnings of AICD in breast cancer enhances the arsenal of potential therapeutic tools, offering an unparalleled window for innovative interventions. Essentially, this paper reveals the hitherto enigmatic link between AICD and breast cancer, potentially leading to revolutionary progress in personalized oncology.

Bladder trauma: a guideline of the guidelines.

OBJECTIVES: To identify and review the most up-to-date guidelines pertaining to bladder trauma in a unifying document as an updated primer in the management of all aspects relating to bladder injury. METHODS: In accordance with the PRISMA statement, the most recent guidelines pertaining to bladder injury were identified and subsequently critically appraised. An electronic search of PubMed and Scopus databases was carried out in September 2023. RESULTS: A total of six guidelines were included: European Association of Urology (EAU) guidelines on urological trauma (2023), EAU guidelines on paediatric urology (2022), Urotrauma: American Urological Association (AUA) (2020), Kidney and Uro-trauma: World Society of Emergency Surgery and the American Association for the Surgery of Trauma (WSES-AAST) guidelines (2019), Management of blunt force bladder injuries: A practice management guideline from the Eastern Association for the Surgery of Trauma (EAST) (2019), and EAU guidelines on iatrogenic trauma (2012). Recommendations were summarised with the associated supporting level of evidence and strength of recommendation where available. CONCLUSION: Several widely recognised professional organisations have published guidelines relating to the diagnosis, investigation, classification, management, and follow-up related to bladder injury. There is consensus amongst all major guidelines in terms of diagnosis and management but there is some discrepancy and lack of recommendation with regards to the follow-up of bladder injuries, iatrogenic bladder injury, paediatric bladder trauma, and spontaneous bladder rupture. The role of increasing minimally invasive techniques seem to be gaining traction in the select haemodynamically stable patient. Further research is required to better delineate this treatment option.

The impact of diabetes and hypertension on renal allograft survival- A single center study.

Background: To determine the impact of pre-transplant diabetes mellitus (DM) and post-transplant hypertension (HT) at 1 year on renal allograft survival in all adult first kidney-only (FKO) transplant recipients at a single transplant center in Johannesburg, South Africa. Materials and methods: A retrospective review was conducted of all adult FKO transplant procedures at the Charlotte Maxeke Johannesburg Academic Hospital transplant unit between 1966 and 2013. Results: During the stipulated timeframe, 1685 adult FKO transplant procedures were performed. Of these, 84.1% were from deceased donors (n = 1413/1685). The prevalence of pre-transplant DM transplant recipients with no missing or incomplete records was 6.5% (n = 107/1625). Of the total cohort of 1685 adult FKO transplant recipients, 63.6% of those with no missing data survived to 1 year (n = 1072/1685). The prevalence of HT at 1-year post-transplant was 53.6% (n = 503/1072). HT at 1-year post-transplant, even after adjusted survival analysis, proved a significant risk factor for renal allograft loss (hazard ratio, 1.63; 95% confidence interval, 1.37-1.94) (p < 0.0001). Similarly, after adjusted survival analysis, the risk of renal allograft loss within the pre-transplant DM group was significantly higher (p = 0.043; hazard ratio, 1.26; 95% confidence interval, 1.01-1.58). Conclusions: This study identified pre-transplantation diabetes mellitus and post-transplantation HT as significant risk factors for graft loss within the population assessed in this region of the world. These factors could potentially be used as independent predictors of renal graft survival.

Miniaturizing the approach to upper tract renal calculi: Is smaller always better? A narrative review.

Newer modalities for treating upper tract urinary stones focus on maintaining and improving outcomes, reducing complications, and optimizing patient care. This narrative review aims to outline novel miniaturized endourological innovations for managing upper tract calculi.

The "ins and outs" of the magnetic ureteral stent: A novel innovation in Endourology.

Background: Ureteral stents play a major role in maintaining ureteral patency. Various innovations are advocated in the design and subsequent removal of traditional double-J ureteral stents, such as the magnetic-end double-J ureteral stent (MEDJUS). This stent facilitates outpatient removal using a magnetic stent removal device. This systematic review was conducted to analyze the published role, efficacy, and outcomes of MEDJUS. Materials and methods: After PROSPERO registration (CRD42021235739), an electronic database search (PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science) was performed on December 31, 2020. The search terms were as follows: "magnetic," "ureteric," "stent," "double-J," "urotech," and "Black-Star." Results: Nine studies with a total of 685 patients were included in the systematic review. The total number of MEDJUS procedures used was 498 (73%) compared to the 187 (27%) traditional double-J stent method. Magnetic-end double-J ureteral stent extraction failure was reported in 8 cases (1.61%). Compared with traditional stents, MEDJUS showed a cost benefit in 5/5 studies. Better pain scores (during stent in situ) and (at stent removal) were observed in 2/3 and 3/4 of the studies, respectively. Conclusions: Magnetic-end double-J ureteral stent may serve as a viable alternative to traditional double-J stents, offering cost and pain benefits with similar rates of complications. Magnetic-end double-J ureteral stent also offers relative ease of extraction and a reduced need for inpatient removal. This ambulatory stent removal technique has forged its use in modern urological practice.

Aquablation in men with benign prostate hyperplasia: A systematic review and meta-analysis.

Objective: The aim of the study is to investigate improvements in lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH) treated with prostatic Aquablation. Materials and methods: We performed a literature search of clinical trials using the MEDLINE, Embase, and Cochrane Library databases and retrieved published works on Aquablation for the treatment of BPH up to August 2021. Unpublished works, case reports, conference proceedings, editorial comments, and letters were excluded. Risk of bias was assessed using the ROBINS-I tool. Raw means and mean differences were meta-analyzed to produce summary estimates for pre- versus post-International Prostate Symptom Scores, maximum flow rate, and male sexual health questionnaire value changes. An inverse-variance weighted random effects model was used. Results: Seven studies were included in this review (n = 551 patients) that evaluated various urological parameters. At 3 months, the International Prostate Symptom Scores raw mean difference from baseline was -16.475 (95% confidence interval [CI], -15.264 to -17.686; p < 0.001), with improvements sustained for 12 months. Similarly, maximum flow rate improved by +1.96 (95% CI, 10.015 to 11.878; p < 0.001) from pre to 3 months postoperatively. In addition, the male sexual health questionnaire change pooled effect size was -0.55 (95% CI, -1.621 to 0.531; p = 0.321) from preintervention to postintervention at 3 months. Meta-analyses of some outcomes showed large statistical heterogeneity or evidence of publication bias. Conclusions: Aquablation seems to improve lower urinary tract symptoms in men with BPH while providing relatively preserved sexual function. Further research is required to confirm these preliminary results.

Periodontitis treatment (surgical and nonsurgical) effects on glycemic control: A review and meta-analysis.

Background: Periodontitis is the sixth most prevalent chronic disease. Literature suggests a relationship between diabetes and periodontitis and when coexist may aggravate each other deleterious consequences. Therefore, we aimed to assess the effects of periodontitis treatment on glycemic control. Materials and Methods: A systematic literature search was conducted in PubMed, Cochrane Library, and the first 100 articles in Google Scholar from January 2011 to October 2021. The terms periodontitis, periodontal treatment, diabetes mellitus, nonsurgical treatment, glycated hemoglobin (HbA1c) were used, with the Protean "AND" and "OR." The titles, abstracts, and references of the included studies were screened. Any discrepancy was solved by an agreement between researchers. Out of 1059 studies retrieved, 320 stands after the removal of duplication, from them, 31 full texts were screened and only 11 studies were included in the final meta-analysis. Results: In the present meta-analysis, 11 studies (1469 patients included) were pooled, and the overall effect showed that periodontitis treatment improved the HbA1c, odd ratio, -0.024, 95% confidence interval, -0.42-.06, P value, 0.009, Chi-square, 52.99. However, substantial heterogeneity was observed, P value, < 0.001, I2 for heterogeneity 81%. Conclusion: Periodontitis treatment improved the HbA1c among patients with diabetes and poor glycemic control. Screening of this common disease is important in diabetes holistic care.

Résumé Contexte: La parodontite est la sixième maladie chronique la plus répandue. La littérature suggère une relation entre le diabète et la parodontite et lorsqu'ils coexistent peuvent aggraver les uns les autres des conséquences délétères. Par conséquent, nous avons cherché à évaluer les effets du traitement de la parodontite sur le contrôle glycémique. Matériels et méthodes: Une recherche documentaire systématique a été menée dans PubMed, Cochrane Library et les 100 premières articles dans Google Scholar de janvier 2011 à octobre 2021. Les termes parodontite, traitement parodontal, diabète sucré, non chirurgical traitement, l'hémoglobine glyquée (HbA1c) a été utilisée. Avec le protéiforme " ET " et " OU ". Les titres, résumés et références des documents inclus études ont été passées au crible. Toute divergence a été résolue par un accord entre les chercheurs. Sur 1059 études récupérées, 320 stands après la suppression des doublons, parmi eux, 31 textes intégraux ont été passés au crible et seules 11 études ont été incluses dans la méta-analyse finale. Résultats: Dans le présente méta-analyse, 11 études (1469 patients inclus) ont été regroupées et l'effet global a montré que le traitement de la parodontite améliorait l'HbA1c, rapport des cotes, −0,024, intervalle de confiance à 95 %, −0,42−0,06, valeur P, 0,009, Chi-carré, 52,99. Cependant, une grande hétérogénéité a été observé, valeur P, < 0,001, I2 pour l'hétérogénéité 81%. Conclusion: Le traitement de la parodontite a amélioré l'HbA1c chez les patients diabétiques et un mauvais contrôle glycémique. Le dépistage de cette maladie courante est important dans les soins holistiques du diabète. Mots-clés: Diabète sucré, contrôle glycémique, parodontite.

The Anticancer Potential of Psidium guajava (Guava) Extracts.

The fruits, leaves, and bark of the guava (Psidium guajava) tree have traditionally been used to treat a myriad of ailments, especially in the tropical and subtropical regions. The various parts of the plant have been shown to exhibit medicinal properties, such as antimicrobial, antioxidant, anti-inflammatory, and antidiabetic activities. Recent studies have shown that the bioactive phytochemicals of several parts of the P. guajava plant exhibit anticancer activity. This review aims to present a concise summary of the in vitro and in vivo studies investigating the anticancer activity of the plant against various human cancer cell lines and animal models, including the identified phytochemicals that contributes to their activity via the different mechanisms. In vitro growth and cell viability studies, such as the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the sulforhodamine B (SRB) assay, and the trypan blue exclusion test, were conducted using P. guajava extracts and their biomolecules to assess their effects on human cancer cell lines. Numerous studies have showcased that the P. guajava plant and its bioactive molecules, especially those extracted from its leaves, selectively suppress the growth of human cancer cells without cytotoxicity against the normal cells. This review presents the potential of the extracts of P. guajava and the bioactive molecules derived from it, to be utilized as a feasible alternative or adjuvant treatment for human cancers. The availability of the plant also contributes towards its viability as a cancer treatment in developing countries.

Spontaneous (idiopathic) rupture of the urinary bladder: a systematic review of case series and reports.

OBJECTIVES: To perform a systematic review of all cases of spontaneous rupture of the urinary bladder (SRUB) and to describe the demographic data, associated comorbidities, clinical presentation, diagnosis, relevant laboratory findings, associated factors, management, morbidity and mortality associated with the presentation of SRUB. METHODS: The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). A search was carried out across the following electronic databases: PubMed, Web of Science, Scopus, Google Scholar and the Cochrane Database of Systematic Reviews. Full texts of selected studies were analysed, and data extracted. The review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: A total of 278 articles comprising 240 case reports and 38 case series, with a total of 351 patients were included. The median (interquartile range [IQR]) age of all included patients was 47.5 (33-65) years. The median (IQR) time to presentation was 48 (24-96) h, with the major presenting symptom being abdominal pain (76%). In patients in whom the diagnosis was made prior to any intervention, the condition was misdiagnosed in 64% of cases. The diagnosis was confirmed during explorative open surgery in 42% of cases. Pelvic radiation (13%) and alcohol intoxication (11%) were the most common associated factors. Intraperitoneal rupture (89%) was much more common, with the dome of the bladder being most frequently involved (55%). The overall mortality was 15%. CONCLUSION: This review identified a number of key factors that appear to be associated with an increased incidence of SRUB. It also emphasized the high rate of misdiagnosis and challenge in confirming the diagnosis. Overall, it highlighted the importance of the need for increased awareness and maintaining a high index of suspicion for this condition.

mHealth app usage amongst paediatric department doctors in South Africa.

Background: Smartphone and mobile health (mHealth) applications (apps) have become an integral part of the day-to-day function of healthcare professionals, allowing quick, comprehensive, and up-to-date access to current clinical guidelines and other reference material. Objective: To evaluate the extent and nature of use of mHealth apps by paediatric department doctors in South Africa. Methods: E-mails requesting study participation were sent out to 285 paediatric department doctors employed at six hospitals affiliated to the University of the Witwatersrand. Willing participants were directed to complete the online study questionnaire. Results: A total of 150 respondents completed the questionnaire. All respondents owned a mobile device and already had one or more mHealth apps, 95.3% were unaware of any regulatory body responsible for regulating the use of mHealth apps, 86.0% did not have access to free Wi-Fi at work and 87.3% used an mHealth app at least once daily. Drug dosing (81.3%), diagnostic (59.3%) and clinical decision-making (44.7%) apps were the most common app categories with Medscape® (62.0%) and EMGuidance® (41.3%) being the most frequently used apps. Peer recommendation (76.0%), app credibility (74.0%) and app functionality (66.0%) were the most common factors that were considered by respondents prior to downloading or using an mHealth app. Conclusion: Medical apps are frequently used among paediatric medical doctors of all ranks. Drug dosing, diagnostic and clinical decision-making apps are the most common app categories in use. Improved awareness of the regulations pertaining to the use of mHealth apps amongst doctors is required.

Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.

Adenosine triphosphate (ATP) induced cell death (AICD) is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions. This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology. This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer. This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis, deciphering the intricate mechanisms governing AICD, elucidating its intricate involvement in cancer signaling pathways, and scrutinizing validated key genes. Moreover, the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.

The Effect of Aflatoxin B1 on Tumor-Related Genes and Phenotypic Characters of MCF7 and MCF10A Cells.

The fungal toxin aflatoxin B1 (AB1) and its reactive intermediate, aflatoxin B1-8, 9 epoxide, could cause liver cancer by inducing DNA adducts. AB1 exposure can induce changes in the expression of several cancer-related genes. In this study, the effect of AB1 exposure on breast cancer MCF7 and normal breast MCF10A cell lines at the phenotypic and epigenetic levels was investigated to evaluate its potential in increasing the risk of breast cancer development. We hypothesized that, even at low concentrations, AB1 can cause changes in the expression of important genes involved in four pathways, i.e., p53, cancer, cell cycle, and apoptosis. The transcriptomic levels of BRCA1, BRCA2, p53, HER1, HER2, cMyc, BCL2, MCL1, CCND1, WNT3A, MAPK1, MAPK3, DAPK1, Casp8, and Casp9 were determined in MCF7 and MCF10A cells. Our results illustrate that treating both cells with AB1 induced cytotoxicity and apoptosis with reduction in cell viability in a concentration-dependent manner. Additionally, AB1 reduced reactive oxygen species levels. Phenotypically, AB1 caused cell-cycle arrest at G1, hypertrophy, and increased cell migration rates. There were changes in the expression levels of several tumor-related genes, which are known to contribute to activating cancer pathways. The effects of AB1 on the phenotype and epigenetics of both MCF7 and MCF10A cells associated with cancer development observed in this study suggest that AB1 is a potential risk factor for developing breast cancer.