A Comparative Analysis of the Quality of Root Canal Fillings of In Vivo Studies Conducted in Saudi Arabia and Worldwide: A Systematic Review.

Aim: Root canal treatment (RCT) is a common procedure practiced daily by dentists worldwide. The current systematic review aimed to evaluate and compare clinical studies on the quality of root canal fillings (RCFs) carried out by dentists with different levels of experience conducted worldwide with those conducted specifically in Saudi Arabia (SA). Materials and Methods: A full literature search was conducted in Clarivate Analytics' Web of Science, Elsevier's Scopus, Embase, CINHAL, and PubMed, without a restriction to studies published before January 2015. Also, a manual search was carried out by checking papers that may have been missed during the electronic search. The following keywords were used: [(quality of root canal filling(s)) OR (quality of root canal obturation)) and dental practitioners as (general dental practitioners; final year students; endodontist; specialist) AND (root canal obturation) OR (endodontic treatment)]. Parameters of the quality of RCFs, such as length, density, and taper, were assessed and counted. Results: A total of 13 worldwide and nine SA studies were included in this review, published between 2015 and 2023. Molars were the most treated teeth, at 42.3% and 40.2% for the worldwide and SA studies, respectively. Cases treated by final year students had the highest percentage, at 60.0% for both study groups. The percentages of acceptable quality, with regard to the length, density, and taper of RCFs, were 70.9%, 77.6%, and 84.3%, and 73.2%, 64.6%, and 67.8% for the worldwide and SA studies, respectively. Conclusion: The overall acceptable quality of RCFs was marginally higher in worldwide studies than in SA studies. Both prevalences can be considered as good, which indicates that the quality of RCFs is moving in the right direction.

Synergistic biochar and Serratia marcescens tackle toxic metal contamination: A multifaceted machine learning approach.

Metal contamination in soil poses environmental and health risks requiring effective remediation strategies. This study introduces an innovative approach of synergistically employing biochar and bacterial inoculum of Serratia marcescens to address toxic metal (TM) contamination. Physicochemical, enzymatic, and microbial analyses were conducted, employing integrated biomarker response (IBR) and machine-learning approaches for toxicity estimation. The combined application significantly reduced the Cd, Cr, and Pb concentrations by 71.6, 31.2, and 57.1%, respectively, while the Cu concentration increased by 85% in the individual Serratia marcescens treatment. Biochar enhanced microbial biomass by 33-44% after 25 days. Noteworthy physicochemical improvements included a 44.7% increase in organic content and a decrease in pH and electrical conductivity. The K⁺ and Ca2⁺ concentrations increased by 196.9 and 21.6%, respectively, while the Mg2⁺ content decreased by 86.4%. Network analysis revealed intricate relationships, displaying direct and indirect negative correlations between metals and soil physicochemical parameters. The IBR index values indicated effective mitigation of TM toxicity in Serratia marcescens and biochar with individual and combined treatments. Binary classification demonstrated high sensitivity (80.1%) and specificity (80.5%) in identifying TM-contaminated soil. These findings indicate significant biochar- and Serratia marcescens-induced impacts on toxic metal availability, physicochemical properties, and enzymatic activities in metal-contaminated soil, suggesting that blending soil with biochar and microorganisms is an effective remediation strategy.

Piecing together Pakistan's health system and global health security.

Pakistan's health system has a critical role to play in global health security, however, it faces numerous structural and systemic challenges while contributing to international health efforts. Understanding the dynamics of health system is essential for developing effective strategies to prevent, detect, and respond to health emergencies, ensuring regional stability, and the overall global health security This paper documents the strengths and weaknesses of Pakistan's health systems, the impact of the COVID-19 pandemic, challenges such as funding constraints and fragmented healthcare delivery, threats including antimicrobial resistance, and the importance of international collaboration. Anti-microbial particularly multi-drug resistance, food safety in emergencies, surge capacity of the frontline workforce, patient safety at the health care facilities to curtail healthcare associated infections, and strengthening the points of entry are still the areas that need special attention. To optimise the system's performance, governance and accountability mechanisms are necessary to be put in place under the auspices of national public health agency. Pakistan has the potential to transform its health system by addressing these critical areas and improve its preparedness and readiness for any future health emergency of this scale.

Knowledge and Awareness of Adults towards Nocturnal Enuresis in Children among the Medina Population.

Background: Nocturnal Enuresis (NE) is a common problem among children that is stressful for both the child and adults. There is a lack of adults' knowledge and awareness of the NE condition. Objective: This study aimed to evaluate the adults' knowledge and awareness of NE in Medina City, Saudi Arabia. Method: A cross-sectional observational study was conducted among adults in Medina through September and October 2023, using a questionnaire composed of socio-demographic characteristics and adults' knowledge and awareness of NE. A statistical analysis was performed using SPSS software. Results: The study was conducted among 553 adults in Medina, with a mean (standard deviation [SD]) age of 37.69 (10.775). Most participants (94.8%) were Saudi nationals, of which 84.4% were females, 76.3% were married, and 97.1% were urban residents with university degrees (80.3%). The mean (SD) total score of knowledge and awareness was 4.69 (1.783) out of 9 and 6.49 (2.167) out of 12, respectively. Being female (p < 0.001), with a university degree (p = 0.002), and knowing about enuresis in children (p = 0.011) are significant factors affecting adults' knowledge with higher scores than others. Conclusions: An inadequate knowledge and awareness level of NE in children was revealed among adults living in Medina City, Saudi Arabia. These results emphasize the need for targeted educational campaigns to enhance adults' knowledge and awareness of enuresis.

Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model.

BACKGROUND: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1ß), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Sex differences in altmetric attention scores and traditional impact metrics of top-cited general surgery literature: Cracks in the ceiling?

BACKGROUND: Sex disparities have previously been identified in surgical academia. This study examines sex differences in the top-cited contemporary general surgery articles and compares Altimetric Attention Score (AAS) and other impact metrics between male and female corresponding authors (CAs). METHODS: We conducted a bibliometric analysis of the 100 most cited articles published between 2019 and 2021 in each of the top 10 general surgery journals based on the 2021 Journal Impact Factor. Impact metrics included AAS, citation count, and H-index of the CA. We used multivariable regression analyses to investigate whether the sex of the CA or first author (FA) was independently associated with AAS and citation count. RESULTS: Among 1000 articles, 23.1% had female CAs and 27.4% female FAs. Female CA articles had higher AAS (13.0 [2.0-63.0] vs. 8.0 [1.0-28.5]; p < 0.001) and lower H-indices (24.0 [11.0-45.0] vs. 31.0 [17.0-50.0]; p = 0.015). Although median citation count did not differ by CA sex, articles with Level 1 evidence and a female CA were cited more often (35.5 [24.0-85.0] vs. 25.0 [16.0 vs. 46.0]; p < 0.05). In multivariable regression, female CA articles had higher AAS (OR: 1.002 [95% CI: 1.001-1.004]) and lower H-index (OR: 0.987 [95% CI: 0.977-0.997]). CONCLUSION: Despite having similar citation counts, articles authored by female CAs exhibit higher AAS scores compared to those authored by their male counterparts. While it is heartening that research authored by female surgeons achieves significant visibility, it remains to be understood how this translates into academic impact and scholarly recognition.

Severe Renal Impairment in a Patient with Recent Rheumatoid Arthritis Diagnosis following Methotrexate Initiation: A Case Report.

Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently treated with immunosuppressive agents such as methotrexate (MTX). Although MTX is generally well-tolerated, it can lead to adverse effects, including renal impairment. We present a case of a patient with newly diagnosed RA who developed severe renal impairment shortly after initiating MTX therapy. A 50-year-old male with recently diagnosed RA presented with vomiting, skin itching, mouth ulcers, and a pruritic rash, all occurring shortly after starting MTX treatment. These symptoms led to acute kidney injury (AKI), necessitating hemodialysis. The patient's symptoms and laboratory findings were indicative of ANCA-associated small-vessel vasculitis with a picture of rapidly progressive glomerulonephritis (RPGN). Treatment included discontinuation of MTX, hemodialysis, immunosuppressive therapy with corticosteroids and cyclophosphamide, and patient education. This case emphasizes the need for close monitoring of RA patients initiated on MTX therapy and prompt evaluation of renal function. Clinicians should be vigilant for signs of renal impairment and be prepared to initiate appropriate interventions, including discontinuation of MTX and consideration of immunosuppressive therapy, to optimize patient outcomes. Further research is warranted to understand better the mechanisms underlying renal complications in RA patients receiving MTX treatment.

Prediction of Diabetes and Prediabetes among the Saudi Population Using a Non-Invasive Tool (AUSDRISK).

Background and Objectives: Screening for type 2 diabetes mellitus (DM2) aims to identify asymptomatic individuals who may be at a higher risk, allowing proactive interventions. The objective of this study was to predict the incidence of DM2 and prediabetes in the Saudi population over the next five years. Materials and Methods: The study was conducted in the Aseer region through August 2023 using a cross-sectional survey for data collection. A multistage stratified random sampling technique was adopted, and data were collected through face-to-face interviews using the validated Arabic version of the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Results: In total, 652 individuals were included in the study. Their mean age was 32.0 ± 12.0 years; 53.8% were male, 89.6% were from urban areas, and 55.8% were single. There were statistically significant differences between males and females in AUSDRISK items, including age, history of high blood glucose, use of medications for high blood pressure, smoking, physical activity, and measurements of waist circumference (p < 0.05). Based on AUSDRISK scores, 46.2% of the included participants were predicted to develop impaired glucose tolerance within the coming five years (65.8% among females vs. 23.6%), and 21.9% were predicted to develop DM2 (35.6% among males vs. 6.0% among females); this difference was statistically significant (p = 0.0001). Conclusions: Urgent public health action is required to prevent the increasing epidemic of DM2 in Saudi Arabia.

Correction: Men's knowledge, attitude, and barriers towards emergency contraception: A facility based cross-sectional study at King Saud University Medical City.

[This corrects the article DOI: 10.1371/journal.pone.0249292.].

Efficacy and Safety of Lotilaner Ophthalmic Solution (0.25%) for the Treatment of Demodex Blepharitis: A GRADE Assessed Systematic Review and Meta-Analysis of Observational & Experimental Studies.

PURPOSE: Several treatments have been in use for Demodex blepharitis, before the discovery of lotilaner, like tea tree oil and antibiotics; however, they either have irritable effects or systemic adverse effects, respectively. Lotilaner, a novel ectoparasiticide, has been proposed as a treatment for patients grappling with Demodex blepharitis. This review aims to assess the safety and efficacy of lotilaner in the treatment of Demodex blepharitis. DESIGN: Systematic review and meta-analysis. METHODS: An extensive search was conducted on PubMed, Cochrane Library, Scopus, and Google Scholar to find relevant literature till July 31, 2023 following the PRISMA guidelines. A total of 143 articles were retrieved by database searching, out of which 6 studies met the inclusion criteria and were included in the review. Four randomized controlled trials were included in the meta-analysis of mite eradication incidence. The review is registered with PROSPERO: CRD42023459997. RESULTS: Lotilaner is effective in eradicating Demodex mites in individuals suffering from Demodex blepharitis according to RR for the intervention versus the control group of 3.55 (95% confidence interval [CI]: 2.87-4.40, P < .00001, I2 = 0%). The meta-analysis of clinically meaningful collarette score revealed the summary RR for the intervention versus the control group was 3.15 (95% CI: 2.56-3.89, P < 0.00001, I2 = 27%). In conclusion, the results of the included studies were comparable and consistent. CONCLUSIONS: Our results indicated that lotilaner is an effective, well-tolerated, and promising drug in treating patients with Demodex blepharitis. Lotilaner administration and cost-effectiveness should now be contemplated for the study population as these constituents have a vital impact on its treatment success.

Associations of overweight and obesity with the risk of cardiovascular disease according to metabolic risk factors among middle-aged Japanese workers: The Aichi Workers' cohort study.

BACKGROUND: The association between obesity and cardiovascular disease (CVD) remains unclear, particularly for those with established CVD risk factors. We analyzed follow-up data from the Aichi Workers' Cohort Study. We studied the association between the degree of obesity and risk of CVD and its subtypes specifically among individuals with hypertension, hyper-low-density lipoprotein (LDL)-cholesterolemia, or diabetes. METHODS: Pooled data of 8972 adults (7076 men and 1896 women) who were recruited between 2002 and 2008 were used in the current analysis. We used multivariable Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between the degree of obesity assessed with body mass index (BMI) and the risk of CVD and its subtypes, i.e., coronary heart disease (CHD) and stroke. RESULTS: During a median of 12 years, there were 197 CVDs (80 CHDs and 117 strokes). BMI ≥ 27.5 compared to 21.0-22.9 kg/m2 was positively and significantly associated with the risks of CVD, CHD, and total stroke. Hypertension, hyper-LDL-cholesterolemia, and diabetes mediated 15.9%, 5.8%, and 8.7% of obesity-CVD associations, respectively, and 28.3% by their combination. In the stratified analyses by the presence of risk factors, BMI ≥ 25.0 (overweight/obesity) compared to BMI < 25 kg/m2 was associated with a higher risk of CVD in those with and without hypertension, but only with hyper-LDL-cholesterolemia, and without diabetes. CONCLUSIONS: Overweight/obesity was associated with the risk of CVD and its subtypes. About 30% of the risk was explained by hypertension, hyper-LDL-cholesterolemia, and diabetes, of which hypertension accounted for approximately the half of the explained risk. However, overweight/obesity increased the risk of CVD even in those without hypertension. These findings highlight the importance of controlling and preventing overweight/obesity regardless of chronic disease status.

Abdominal distention, immunopositivity, and aggressive nature: A rare Ewing's sarcoma of the adrenal gland.

This case report describes a 32-year-old Pakistani male patient with an Ewing sarcoma (ES) of the adrenal gland. Presenting complaints were abdominal distention, pain, low-grade fever, and weight loss. Initial studies, including imaging and tumor markers, ruled out any other possible origins of the mass. A percutaneous biopsy verified the tumor's neuroendocrine origin. Extensive involvement of nearby anatomical structures was discovered through exploratory laparotomy, rendering total resection difficult. Based on the presence of malignant, round, blue cells that were positive for specific immunostaining markers, the histopathology report supported the diagnosis of an ES with a staging of T3N0M0. Chemotherapy, in accordance with the VAC-IE protocol, was administered after debulking surgery. Subsequent imaging and close monitoring revealed no metastatic or residual tumors. Adrenal ES is an uncommon, aggressive tumor that mandates prompt diagnosis and management. This case report highlights the value of early detection and multimodal therapy in enhancing patient outcomes for this rare malignancy.

Cryptolepine Analog Exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway.

BACKGROUND: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative. OBJECTIVE: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice. METHODS: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined. RESULTS: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs. CONCLUSION: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.

Effectiveness and safety of mexiletine versus placebo in patients with myotonia: a systematic review and meta-analysis.

BACKGROUND: The rare nature of dystrophic and non-dystrophic myotonia has limited the available evidence on the efficacy of mexiletine as a potential treatment. To address this gap, we conducted a systematic review and meta-analysis to evaluate the effectiveness and safety of mexiletine for both dystrophic and non-dystrophic myotonic patients. METHODS: The search was conducted on various electronic databases up to March 2023, for randomized clinical trials (RCTs) comparing mexiletine versus placebo in myotonic patients. A risk of bias assessment was carried out, and relevant data was extracted manually into an online sheet. RevMan software (version 5.4) was employed for analysis. RESULTS: A total of five studies, comprising 186 patients, were included in the meta-analysis. Our findings showed that mexiletine was significantly more effective than placebo in improving stiffness score (SMD = - 1.19, 95% CI [- 1.53, - 0.85]), as well as in reducing hand grip myotonia (MD = - 1.36 s, 95% CI [- 1.83, - 0.89]). Mexiletine also significantly improved SF-36 Physical and Mental Component Score in patients with non-dystrophic myotonia only. Regarding safety, mexiletine did not significantly alter ECG parameters but was associated with greater gastrointestinal symptoms (GIT) compared to placebo (RR 3.7, 95% CI [1.79, 7.64]). Other adverse events showed no significant differences. CONCLUSION: The results support that mexiletine is effective and safe in myotonic patients; however, it is associated with a higher risk of GIT symptoms. Due to the scarcity of published RCTs and the prevalence of GIT symptoms, we recommend further well-designed RCTs testing various drug combinations to reduce GIT symptoms.

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations.

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 µg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 µM and melphalan at CC50 = 36.3 µM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 µg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera's potential as an affordable source of therapeutic agents for a range of oral malignancies.

Study to Determine the Prevalence of Menstrual Migraine in Reproductive-Age Women in Saudi Arabia.

BACKGROUND: Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50-60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5-8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks. OBJECTIVES: To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia. METHODOLOGY: A cross-sectional community-based study was conducted on reproductive-aged (18-50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia. RESULTS: Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition. CONCLUSIONS: Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

Comparative Analysis of Three Nickel-Titanium Rotary Files in Severely Curved L-Shaped Root Canals: Preparation Time, Aberrations, and Fracture Rates.

Background: This simulated study of 30 severely curved L-shaped root canals aimed to compare preparation time, aberrations, width measurements, and fractured files of three nickel-titanium (Ni-Ti) files, namely, ProTaper, ProTaper Next (PTN), and WaveOne (WO). Methods: Thirty simulated L-curved root canals of resin blocks were randomly divided into three groups. The canals were prepared to a tip size of 25 using ProTaper, PTN, and WO rotary file systems. Pre- and post-operative views for each sample were captured by a professional camera at a standardized distance and position. Blue India ink was injected into the pre-operative canals, and red India ink was injected into the post-operative canals to give a clear superimposition image. Five points were assessed through the halfway of the canal to the orifice (area between the beginning of curvature and apical end point). Preparation time, aberrations, width measurements, and fractured files were recorded and analyzed. Results: Mean preparation time was longest in ProTaper (4.89±0.68 minutes). PTN and WO were the fastest in preparing the canals (about 3 minutes). A statistically significant difference was found between WO and ProTaper & PTN and ProTaper (p=0.000), while the difference was non-significant (p > 0.05) between WO and PTN. Nine aberrations consisting of three zips, one ledge and one outer widening were related to ProTaper, while WO recorded a ledge and fractured file, but for PTN system, it verified an outer widening and ledge. Only one WO file fractured, with no deformation observed in the other instruments. No significance was recorded among the width measurements in the different levels. Conclusion: ProTaper next achieved faster cutting than the ProTaper and WO file systems. PTN maintained the best apical termination position and produced the least canal aberration, followed by WO and ProTaper.

Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules.

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.

Structure-activity relationships for the G-quadruplex-targeting experimental drug QN-302 and two analogues probed with comparative transcriptome profiling and molecular modeling.

The tetrasubstituted naphthalene diimide compound QN-302 binds to G-quadruplex (G4) DNA structures. It shows high potency in pancreatic ductal adenocarcinoma (PDAC) cells and inhibits the transcription of cancer-related genes in these cells and in PDAC animal models. It is currently in Phase 1a clinical evaluation as an anticancer drug. A study of structure-activity relationships of QN-302 and two related analogues (CM03 and SOP1247) is reported here. These have been probed using comparisons of transcriptional profiles from whole-genome RNA-seq analyses, together with molecular modelling and molecular dynamics simulations. Compounds CM03 and SOP1247 differ by the presence of a methoxy substituent in the latter: these two compounds have closely similar transcriptional profiles. Whereas QN-302 (with an additional benzyl-pyrrolidine group), although also showing down-regulatory effects in the same cancer-related pathways, has effects on distinct genes, for example in the hedgehog pathway. This distinctive pattern of genes affected by QN-302 is hypothesized to contribute to its superior potency compared to CM03 and SOP1247. Its enhanced ability to stabilize G4 structures has been attributed to its benzyl-pyrrolidine substituent fitting into and filling most of the space in a G4 groove compared to the hydrogen atom in CM03 or the methoxy group substituent in SOP1247.