Associations between maxillary labial frenum Morphology, Attachment, and Patient-Related clinical factors in Saudi Arabian Adults: Cross-sectional study.

Objective: This study investigated the prevalence of maxillary labial frenum morphologies and attachment types and their associations with various patient-related clinical variables in a population of Saudi Arabian adults. Methods: This study comprehensively examined 100 participants of both genders to categorize frenum types and attachment sites. The following clinical variables were recorded: probing depth, clinical attachment loss, attached gingiva width, overjet, overbite, diastema width, central incisor condition, occlusion, previous orthodontic treatment, and the incidence of gummy smile. Results: The mean age was 32.6 years, and the average diastema width was 0.23 mm. The study found that the simple frenum type was the most common morphology (57 %), and gingival attachment was the most frequent attachment type (54 %). Simple frenum was significantly associated with class I occlusion (p = 0.018), and frenum with nichum was significantly associated with class II occlusion (p = 0.019). Females were more likely to exhibit simple frenum with nodule frenum than males (p = 0.042). Mucosal frenum attachment was significantly correlated with the absence of previous orthodontic treatment (p = 0.042). Conclusion: The study identified a relationship between the features of the maxillary labial frenum and occlusion as well as previous orthodontic treatment. Our findings suggest that understanding each patient's unique frenum features can lead to more effective and personalized dental care, thus improving patient satisfaction.

Bridging the Gaps: The Transformative Effect of Coronavirus Disease 2019 (COVID-19) on Preventive Measures Among Medical and Health Sciences College Students in Madinah, Saudi Arabia.

Background The global impact of coronavirus disease 2019 (COVID-19) has disrupted the activities of medical and health profession education institutions. This study aimed to determine the impact of COVID-19 on medical and health profession education students' knowledge, attitudes, and practices toward preventive measures and their commitment to precautionary measures before, during, and after the pandemic. Materials and methods A cross-sectional study was carried out from January to March 2023 using an online, structured, validated questionnaire survey to gather information from medical and health sciences students from three universities, encompassing five colleges in Madinah, Saudi Arabia. The minimum required sample size was estimated using the Epi Info software as 380. The data was analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States). Statistical tests including Student's t-test, chi-squared test, and analysis of variance (ANOVA) test were applied. Results The findings revealed that personal experiences with COVID-19 infection had a significant impact on students' attitudes and commitment to preventive measures (p<0.05). Among the participants, 172 students (45%) reported having contracted COVID-19. Students with clinical exposure showed a higher level of understanding and adherence to preventive measures (248 students, 68%), compared to pre-clinical students (198 students, 52%) (p<0.05). Positive attitudes were observed toward practices such as sneezing etiquette (289 students, 76%) and flu vaccination (314 students, 83%) (p<0.05). However, negative attitudes were observed toward mask-wearing (155 students, 41%) and social distancing (144 students, 38%), particularly among male students (p<0.05). Conclusion The study provided valuable insights into the impact of the COVID-19 pandemic on medical and health sciences students' knowledge, attitudes, and practices toward preventive measures and the importance of introducing COVID-19 prevention measures in the pre-clinical phase as well as mental health support to promote positive attitudes and enhance adherence to preventive measures.

Thorough examination of the potential biological implications of the cuproptosis-related gene LIPT2 in the prognosis and immunotherapy in pan-cancer.

OBJECTIVES: To elucidate the expression levels and prognostic value of the Lipoyltransferase 2 (LIPT2) gene in a pan-cancer view. METHODOLOGY: Our study comprehensively investigated the role of LIPT2 in pan-cancer, combining bioinformatics analyses with experimental validations. RESULTS: Analysis of LIPT2 mRNA expression across various cancers revealed a significant up-regulation in 18 tumor types and down-regulation in 8 types, indicating its diverse involvement. Prognostic assessment demonstrated a correlation between elevated LIPT2 expression and poorer outcomes in Overall Survival (OS) and Disease-Free Survival (DFS), particularly in Glioblastoma Multiforme (GBM), Liver Hepatocellular Carcinoma (LIHC), and Pheochromocytoma and Paraganglioma (PCPG). Protein expression analysis in GBM, LIHC, and PCPG affirmed a consistent increase in LIPT2 levels compared to normal tissues. Examining the methylation status in GBM, LIHC, and PCPG, we found reduced promoter methylation levels in tumor samples, suggesting a potential influence on LIPT2 function. Genetic mutation analysis using cBioPortal indicated a low mutation frequency (< 2%) in LIPT2 across GBM, LIHC, and PCPG. Immune correlation analysis unveiled a positive association between LIPT2 expression and infiltration levels of immune cells in GBM, LIHC, and PCPG. Single-cell analysis illustrated LIPT2's positive correlation with functional states, including angiogenesis and inflammation. Enrichment analysis identified LIPT2-associated processes and pathways, providing insights into its potential molecular mechanisms. Drug sensitivity analysis demonstrated that elevated LIPT2 expression conferred resistance to multiple compounds, while lower expression increased sensitivity. Finally, RT-qPCR validation in HCC cell lines confirmed the heightened expression of LIPT2 compared to a control cell line, reinforcing the bioinformatics findings. CONCLUSION: Overall, our study highlights LIPT2 as a versatile player in cancer, influencing diverse aspects from molecular processes to clinical outcomes across different cancer types.

Pan-cancer analysis of HS6ST2: associations with prognosis, tumor immunity, and drug resistance.

OBJECTIVES: In this comprehensive study spanning 33 malignancies, we explored the differential expression and prognostic significance of Heparan sulfate 6-O-sulfotransferase 2 (HS6ST2). METHODS: TIMER2, UALCAN, and GEPIA2 were used for the expression analysis. cBioPortal was used for mutational analysis. CancerSEA, STRING, and DAVID, were employed for the single cell sequencing data analysis, protein-protein interaction network development, and gene enrichment analyses, respectively. GSCAlite and RT-qPCR were used for drug sensitivity and expression validation analysis. RESULTS: HS6ST2 exhibited significant (P < 0.05) overexpression in multiple cancers. Prognostically, elevated HS6ST2 expression was significantly associated with poor overall survival (OS) in patients with cervical squamous cell carcinoma (CESC), kidney chromophobe (KICH), lung adenocarcinoma (LUAD), and stomach adenocarcinoma (STAD), emphasizing its potential as a prognostic indicator in these cancers. Moreover, HS6ST2 expression correlated with pathological stages in CESC, KICH, LUAD, and STAD patients. Exploration of genetic alterations using cBioPortal unveiled distinct mutational landscapes, with low mutation frequencies in CESC, KICH, LUAD, and STAD. Additionally, reduced DNA methylation in CESC, KICH, LUAD, and STAD suggested a potential link between hypomethylation and heightened HS6ST2 expression. Analysis of immune cell infiltration revealed a positive correlation between HS6ST2 expression and the infiltration of CD8+ T and CD4+ T cells in CESC, KICH, LUAD, and STAD, highlighting its involvement in the tumor immunology processes. Single-cell functional states analysis demonstrated associations between HS6ST2 and diverse cellular processes. Moreover, gene enrichment analysis revealed the involvement HS6ST2 in crucial cellular activities. GSCAlite analysis underscored the potential of HS6ST2 as a therapeutic target, showing associations with drug sensitivity. Finally, experimental validation through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in LUAD tissues confirmed elevated HS6ST2 expression. CONCLUSION: Overall, this study provides a comprehensive understanding of HS6ST2 in CESC, KICH, LUAD, and STAD, emphasizing its potential as a prognostic biomarker and therapeutic target.

Integrated spectroscopic and computational analyses unravel the molecular interaction of pesticide azinphos-methyl with bovine beta-lactoglobulin.

Organophosphorus are typically hazardous chemicals used in the pharmaceutical, agricultural, and other industries. They pose a serious risk to human life and can be fatal upon direct exposure. Hence, studying the interaction between such compounds with proteins is crucial for environmental, health, and food safety. In this study, we investigated the interaction mechanism between azinphos-methyl (AZM) and ß-lactoglobulin (BLG) at pH 7.4 using a combination of biophysical techniques. Intrinsic fluorescence investigations revealed that BLG fluorescence was quenched in the presence of increasing AZM concentrations. The quenching mechanism was identified as static, as evidenced by a decrease in the fluorescence quenching constant (1.25 × 104, 1.18 × 104, and 0.86 × 104 M-1) with an increase in temperatures. Thermodynamic calculations (ΔH > 0; ΔS > 0) affirmed the formation of a complex between AZM and BLG through hydrophobic interactions. The BLG's secondary structure was found to be increased due to AZM interaction. Ultraviolet -visible spectroscopy data showed alterations in BLG conformation in the presence of AZM. Molecular docking highlighted the significant role of hydrophobic interactions involving residues such as Val43, Ile56, Ile71, Val92, Phe105, and Met107 in the binding between BLG and AZM. A docking energy of -6.9 kcal mol-1, and binding affinity of 1.15 × 105 M-1 suggest spontaneous interaction between AZM and BLG with moderate to high affinity. These findings underscore the potential health risks associated with the entry of AZM into the food chain, emphasizing the need for further consideration of its impact on human health.

Phytochemical screening, antioxidant, immunomodulatory and analgesic potential of aqueous-ethanolic extracts of Euphorbia prostrata ait. and Crotalaria burhia Buch-Ham.

Euphorbia prostrata (E. prostrata) and Crotalaria burhia (C. burhia) are widely found in flora of the Cholistan Desert of Bahawalpur, Pakistan and are traditionally used to treat pain and chronic disease. The current study aimed to evaluate their phytochemical screening, antioxidant activity, in-vivo phagocytic activity, and analgesic activity. Both the plant extracts were investigated for phytochemical screening, Fourier Transform Infrared (FTIR) analysis, in-vitro antioxidant by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) method, in-vivo immunomodulatory activity by macrophages phagocytosis using carbon clearance rate assay and analgesic activity by acetic acid produced writhing method. Phytochemical screening showed the presence of carbohydrates, saponins, tannins, phenols, quinines, proteins, terpenes, glycosides, and alkaloids. FTIR analysis revealed the existence of different functional groups in both extracts. The DPPH method showed that E. prostrata exhibited a high antioxidant potential with an IC50 of 62.5 µg/ml whereas C. burhia showed a lower antioxidant potential. At the dose of 200 mg/kg body weight (b. wt), both the extracts showed a significant increase in the phagocytic index by 5.2 ± 0.2, and, 4.8 ± 0.1 (p < 0.001) respectively which was close to the 100 mg/kg b. wt of the standard drug (Levamisole) 5.4 ± 0.2. Both the extracts at the dose of 200 mg/kg b. wt also significantly reduced the writhing (abdominal contractions) count by 13.7 ± 0.3 and, 25.3 ± 1.5 (p < 0.001), showing 71.8% and 47.6% of reduced analgesic activity compared to the standard drug dicloran (diclofenac sodium), respectively. In conclusion, extracts of both plants indicate their role in the management of various disorders to relieve pain and modulate the immune system.

Probing the interaction mechanisms between sunset yellow dye and trypsin protein leading to amorphous aggregation under low pH conditions.

Protein aggregation poses a significant concern in the field of food sciences, and various factors, such as synthetic food dyes, can contribute to protein aggregation. One such dye, Sunset Yellow (SY), is commonly employed in the food industry. Trypsin was used as a model protein to assess the impact of SY. We employed several biophysical techniques to examine the binding and aggregation mechanisms between SY and trypsin at different pHs. Results from intrinsic fluorescence measurements indicate a stronger interaction between SY and trypsin at pH 2.0 compared to pH 6.0. Turbidity data reveal trypsin aggregation in the presence of 0.05-3.0 mM SY at pH 2.0, while no aggregation was observed at pH 6.0. Kinetic data demonstrate a rapid, lag-phase-free SY-induced aggregation of trypsin. Circular dichroism analysis reveals that trypsin adopts a secondary structure in the presence of SY at pH 6.0, whereas at pH 2.0, the secondary structure was nearly lost with increasing SY concentrations. Furthermore, turbidity and kinetics data suggest that trypsin aggregation depends on trypsin concentrations and pH. Our study highlights potential health risks associated with the consumption of SY, providing insights into its impact on human health and emphasizing the necessity for further research in this field.

Prevalence of nocturnal enuresis among children of Aseer region in Saudi Arabia.

Introduction: Nocturnal enuresis (NE) in children is a very common problem managed in pediatric urology. In this study, we present the prevalence of NE in children in Aseer region in Saudi Arabia. Methodology: This study was conducted as a descriptive cross-sectional survey to estimate the prevalence of NE among 555 Saudi children aged 5-15 years in Aseer region in Saudi Arabia. Data collection was done through a questionnaire, which included questions on sociodemographic data, personal knowledge, enuresis-related characteristics, risk factors, and management modalities. Results: This study identified a prevalence of enuresis of 24% of the study population, most of whom were boys. The majority of the parents had a high educational level. Clinical characteristics of the study population showed: 9% have a family history of NE, 2.2% have a history of neurological disorder, 10.0% have a history of urinary tract infections, 66.8% have associated daytime urgency, 67% have urine-holding behavior, and 19.5% have associated daytime enuresis of the study population. Conclusion: Our study found that 24% of children in the Aseer region in Saudi Arabia have NE. Our study finding helps us to understand the prevalence of NE in Aseer region in Saudi Arabia, and this can be applied to other regions in the kingdom. Furthermore, this finding helps us to understand the need to raise awareness in the community about NE and the need to educate the nonpediatric urologist health-care provider about the best management practice for NE.

The Saudi urological association guidelines on urolithiasis.

Aims: The Saudi Urolithiasis Guidelines are a set of recommendations for diagnosing, evaluating, and treating urolithiasis in the Saudi population. These guidelines are based on the latest evidence and expert consensus to improve patient outcomes and optimize care delivery. They cover the various aspects of urolithiasis, including risk factors, diagnosis, medical and surgical treatments, and prevention strategies. By following these guidelines, health-care professionals can improve care quality for individuals with urolithiasis in Saudi Arabia. Panel: The Saudi Urolithiasis Guidelines Panel consists of urologists specialized in endourology with expertise in urolithiasis and consultation with a guideline methodologist. All panelists involved in this document have submitted statements disclosing any potential conflicts of interest. Methods: The Saudi Guidelines on Urolithiasis were developed by relying primarily on established international guidelines to adopt or adapt the most appropriate guidance for the Saudi context. When necessary, the panel modified the phrasing of recommendations from different sources to ensure consistency within the document. To address areas less well covered in existing guidelines, the panel conducted a directed literature search for high quality evidence published in English, including meta analyses, randomized controlled trials, and prospective nonrandomized comparative studies. The panel also searched for locally relevant studies containing information unique to the Saudi Arabian population. The recommendations are formulated with a direction and strength of recommendation based on GRADE terminology and interpretation while relying on existing summaries of evidence from the existing guidelines.

Design, synthesis, in-vitro biological profiling and molecular docking of some novel oxazolones and imidazolones exhibiting good inhibitory potential against acetylcholine esterase.

Heterocyclic compounds with oxazole and imidazole rings in their structure have disclosed momentous biological aptitudes. Taking into account their superlative attributes, the present study was designed to introduce a new synthetic scheme to make new derivatives with tremendous futuristic pharmacological potentialities. Series of Oxazolones were synthesized by using substituted benzaldehyde with benzyl halides to produce respective benzaldehyde derivatives 1 (a-d) which further reacted with hippuric acid to yield oxazolones 2 (a-e). Newly synthesized oxazolones then reacted with 4-chloroaniline to yield corresponding imidazolones 3 (a-e). All the compounds were characterized by using FTIR and NMR spectroscopic techniques. Docking studies of Compounds were conducted using AutoDock Vina and analyzed with PYMOL. All synthesized oxazolone and imidazolone derivatives exhibited antioxidant potential, demonstrated by their IC50 values compared to ascorbic acid standard. Oxazolone derivatives (2a-2e) exhibited good acetyl cholinesterase inhibitory potential whereas Imidazolone series did not show significant inhibition as shown by their IC50 values compared to donepezil as a standard. Docking studies of all compounds against acetylcholinesterase demonstrated favorable binding affinity, indicating their potential for further in-vivo studies. It is notable that novel compounds of both oxazolones and Imidazolone series exhibited antioxidant potential with maximum percentage inhibition of 75.9 (IC50 12.9 ± 0.0573 µM/mL) by compound 2d while compound 2a showed AChE inhibitory potential with maximum %age inhibition of 75.49 (IC50 7.8 ± 0.0218 µM/mL).Communicated by Ramaswamy H. Sarma.

Rapamycin as a Potential Alternative Drug for Squamous Cell Gingiva Carcinoma (Ca9-22): A Focus on Cell Cycle, Apoptosis and Autophagy Genetic Profile.

Oral cancer is considered as one of the most common malignancies worldwide. Its conventional treatment primarily involves surgery with or without postoperative adjuvant therapy. The targeting of signaling pathways implicated in tumorigenesis is becoming increasingly prevalent in the development of new anticancer drug candidates. Based on our recently published data, Rapamycin, an inhibitor of the mTOR pathway, exhibits selective antitumor activity in oral cancer by inhibiting cell proliferation and inducing cancer cell apoptosis, autophagy, and cellular stress. In the present study, our focus is on elucidating the genetic determinants of Rapamycin's action and the interaction networks accountable for tumorigenesis suppression. To achieve this, gingival carcinoma cell lines (Ca9-22) were exposed to Rapamycin at IC50 (10 µM) for 24 h. Subsequently, we investigated the genetic profiles related to the cell cycle, apoptosis, and autophagy, as well as gene-gene interactions, using QPCR arrays and the Gene MANIA website. Overall, our results showed that Rapamycin at 10 µM significantly inhibits the growth of Ca9-22 cells after 24 h of treatment by around 50% by suppression of key modulators in the G2/M transition, namely, Survivin and CDK5RAP1. The combination of Rapamycin with Cisplatin potentializes the inhibition of Ca9-22 cell proliferation. A P1/Annexin-V assay was performed to evaluate the effect of Rapamycin on cell apoptosis. The results obtained confirm our previous findings in which Rapamycin at 10 µM induces a strong apoptosis of Ca9-22 cells. The live cells decreased, and the late apoptotic cells increased when the cells were treated by Rapamycin. To identify the genes responsible for cell apoptosis induced by Rapamycin, we performed the RT2 Profiler PCR Arrays for 84 apoptotic genes. The blocked cells were believed to be directed towards cell death, confirmed by the downregulation of apoptosis inhibitors involved in both the extrinsic and intrinsic pathways, including BIRC5, BNIP3, CD40LG, DAPK1, LTA, TNFRSF21 and TP73. The observed effects of Rapamycin on tumor suppression are likely to involve the autophagy process, evidenced by the inhibition of autophagy modulators (TGFß1, RGS19 and AKT1), autophagosome biogenesis components (AMBRA1, ATG9B and TMEM74) and autophagy byproducts (APP). Identifying gene-gene interaction (GGI) networks provided a comprehensive view of the drug's mechanism and connected the studied tumorigenesis processes to potential functional interactions of various kinds (physical interaction, co-expression, genetic interactions etc.). In conclusion, Rapamycin shows promise as a clinical agent for managing Ca9-22 gingiva carcinoma cells.

Association of esophageal motility disorder symptoms with Chicago classification versions 3.0 and 4.0 using high-resolution esophageal manometry: A single-center experience from Saudi Arabia.

BACKGROUND: Esophageal motility disorders (EMDs) can significantly impact patients' quality of life. The Chicago Classification (CC) was developed as a robust framework to enable clinicians to better understand and classify the nature of motility disorders. Previous studies have primarily focused on the CC version 3.0 (CCv3.0), and data regarding the correlation between symptoms and CC version 4.0 (CCv4.0) in the Saudi Arabian population are lacking. This study aimed to assess the correlation between symptoms and CCv3.0 and CCv4.0 using high-resolution esophageal manometry (HRM) in Saudi Arabia, to evaluate the diagnostic performance of both classifications. METHODS: A total of 182 patients presenting with esophageal symptoms were included in this study. HRM was performed to assess esophageal motility, and patients' reported symptoms were recorded. The association between HRM findings and symptomatic variables was analyzed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Variability was observed in the diagnostic performance of symptomatic variables for major EMDs. CCv4.0 demonstrated a higher sensitivity for dysphagia than CCv3.0; however, it exhibited lower sensitivity to atypical gastroesophageal reflux disease (GERD) symptoms. Noncardiac chest pain (NCCP) exhibited the highest specificity and PPV, whereas typical GERD symptoms showed lower specificity. CONCLUSION: CCv4.0 demonstrated potential improvements in sensitivity for dysphagia, but lower sensitivity for atypical GERD symptoms, compared with CCv3.0. These insights provide guidance for clinicians in Saudi Arabia and contribute to understanding the diagnostic performance of CCv3.0 and CCv4.0.

Genomic annotation for vaccine target identification and immunoinformatics-guided multi-epitope-based vaccine design against Songling virus through screening its whole genome encoded proteins.

Songling virus (SGLV), a newly discovered tick-borne orthonairovirus, was recently identified in human spleen tissue. It exhibits cytopathic effects in human hepatoma cells and is associated with clinical symptoms including headache, fever, depression, fatigue, and dizziness, but no treatments or vaccines exist for this pathogenic virus. In the current study, immunoinformatics techniques were employed to identify potential vaccine targets within SGLV by comprehensively analyzing SGLV proteins. Four proteins were chosen based on specific thresholds to identify B-cell and T-cell epitopes, validated through IFN-γ epitopes. Six overlap MHC-I, MHC-II, and B cell epitopes were chosen to design a comprehensive vaccine candidate, ensuring 100% global coverage. These structures were paired with different adjuvants for broader protection against international strains. Vaccine constructions' 3D models were high-quality and validated by structural analysis. After molecular docking, SGLV-V4 was selected for further research due to its lowest binding energy (-66.26 kcal/mol) and its suitable immunological and physiochemical properties. The vaccine gene is expressed significantly in E. coli bacteria through in silico cloning. Immunological research and MD simulations supported its molecular stability and robust immune response within the host cell. These findings can potentially be used in designing safer and more effective experimental SGLV-V4 vaccines.

Aggregation and cytotoxicity of food additive dye (Azorubine)-albumin adducts: a multi-spectroscopic, microscopic and computational analysis.

Protein and peptide misfolding is a central factor in the formation of pathological aggregates and fibrils linked to disorders like Alzheimer's and Parkinson's diseases. Therefore, it's essential to understand how food additives, particularly Azorubine, affect protein structures and their ability to induce aggregation. In this study, human serum albumin (HSA) was used as a model protein to investigate the binding and conformational changes caused by azorubine, a common food and drink colorant. The research revealed that azorubine destabilized the conformation of HSA at both physiological (pH 7.4) and acidic (pH 3.5) conditions. The loss of tryptophan fluorescence in HSA suggested significant structural alterations, particularly around aromatic residues. Far UV-CD analysis demonstrated disruptions in HSA's secondary structure, with a notable reduction in α-helical structures at pH 7.4. At pH 3.5, Azorubine induced even more extensive perturbations, resulting in a random coil conformation at higher azorubine concentrations. The study also investigated aggregation phenomena through turbidity measurements, RLS analysis, and TEM imaging. At pH 3.5, larger insoluble aggregates formed, while at pH 7.4, only conformational changes occurred without aggregate formation. Cytotoxicity assessments on neuroblastoma (SH-SY5Y) cells highlighted the concentration-dependent toxicity of albumin aggregates. Molecular dynamics simulations reaffirmed the stable interaction between azorubine and HSA. This research provides valuable insights into the mechanisms by which azorubine influences protein conformations. To further advance our understanding and contribute to the broader knowledge in this area, several future directions can be considered such as exploring other proteins, studying dose-response relationship, gaining mechanistic insights, biological relevance, toxicity assessment, identifying alternative food colorants, and mitigation strategies to prevent adverse effects of azorubine on serum proteins.Communicated by Ramaswamy H. Sarma.

Angiotensin(1-7) attenuates tooth movement and regulates alveolar bone response during orthodontic force application in experimental animal model.

BACKGROUND: Renin-angiotensin system and its ACE2/Ang(1-7)/Mas receptor axis regulates skeletal response to multiple physiological and pathological conditions. Recent research suggested a vital role of Ang(1-7) in regulating alveolar bone metabolism and remodeling. In this context, this study evaluated the effects of the Ang(1-7)/Mas receptor axis on orthodontic tooth movement (OTM) and the alveolar bone response to mechanical load. METHODS: A coil spring was placed between the right maxillary first molar and the anterior tooth of Wistar rats to apply bidirectional mechanical force. Ang(1-7) with or without a specific Mas receptor antagonist (A779) was infused using subcutaneous osmotic pumps (200 and 400 ng/kg/min: respectively). Animals were killed after 5 and 14 days from the OTM procedure after the clinical evaluation of tooth movement and mobility. Morphometric analysis of alveolar bone structure was conducted using micro-CT and the histological picture was evaluated after H&E staining. Moreover, collagen fiber distribution was assessed using Picro-Sirius red stain. In addition, bone samples were collected from the pressure and tension sites around the anterior tooth for gene expression analysis. RESULTS: Ang(1-7) infusion suppressed the tooth movement and mobility after 14 days of the orthodontic force application. Additionally, Ang(1-7) infusion preserved the morphometric and histological structure of the alveolar bone at pressure and tension sides. These effects were abolished by adding A779 infusion. Collagen fiber distribution was dysregulated mainly by the A779 Mas receptor blockage. Ang(1-7) affected the bone formation, remodeling- and vascularity-related genes in the pressure and tension sides, suggesting a prominent suppression of osteoclastogenesis. Ang(1-7) also improved osteoblasts-related genes on the tension side, whereas the osteoclasts-related genes were augmented by A779 on the pressure side. CONCLUSION: Collectively, the activation of Ang(1-7)/Mas receptor axis appears to hinder tooth movement and regulates alveolar bone remodeling in response to mechanical force.

Temporomandibular Disorders among Dental Students in Pakistan: Assessment of Prevalence, Severity, and Associated Factors Based on Questionnaire.

Objective: To evaluate the prevalence, severity, and associated factors of temporomandibular disorder (TMD) among dental students. Methods: This cross-sectional study was performed on undergraduate dental students from four dental colleges in Punjab, Pakistan. Fonseca's questionnaire was used to measure the prevalence and severity of the TMD among the study participants. Bivariate and multiple logistic regression analyses were performed. Results: Of 364 dental students, 323 returned the completed questionnaires and the response rate of the study was 88.7%. The study included 52.6% males and 47.4% females. The prevalence of TMD was 66.9% with mild TMD in 40.90%, moderate TMD in 14.6%, and severe TMD in 11.50% of the participants. Psychological stress (29.6%), malocclusion (20%), and hypersensitivity (19.5%) were common among participants. The mean TMD score of the sample was 31.54 ± 24.86 which was significantly higher among participants with no/school-educated mothers (P=0.021) and fathers (P=0.002). The participants with arthritis (72.81 ± 32.19) and malocclusion (59.46 ± 31.09) and those who received orthodontic treatment (53.21 ± 34.21) demonstrated higher TMD. After controlling for other study variables, the participants with arthritis were 4.71 times more likely to have moderate/severe TMD (P=0.042) than those without arthritis. Similarly, the participants with malocclusion had significantly higher odds (OR = 3.57, P=0.029) of having moderate/severe TMD than those without malocclusion. Conclusion: This sample of dental students demonstrated a high prevalence and severity of TMD. The participants with arthritis and malocclusion demonstrated higher TMD. The study findings underscore the importance of prevention, early diagnosis, and management of TMD among the dental students.

Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.

PURPOSE: The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them. METHODS: We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment. RESULTS: Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options. CONCLUSION: No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.

Bevacizumab, a vascular endothelial growth factor inhibitor, promotes orthodontic tooth movement in an experimental rat model.

Objective: This study aimed to evaluate the impact of bevacizumab on orthodontic tooth movement (OTM) in Wistar rats. Materials and methods: The OTM model was constructed by placing an orthodontic coil spring between the maxillary first molar and anterior tooth. Bevacizumab (Avastin®; 10 mg/kg twice per week) was started one week before the OTM and continued for 3 weeks. After 1 and 2 weeks, OTM distance and anterior tooth mobility were measured. Thereafter, the maxilla was dissected for micro-CT microarchitectural analysis, followed by histological analysis, and tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the distributions of collagen fibers type-I and -III (Col-I and Col-III) were evaluated using Picro-Sirius red staining. Results: Orthodontic force prompted bone resorption and formation on the pressure and tension sides, respectively. Bevacizumab therapy resulted in a 42% increase of OTM, particularly after 2 weeks. Furthermore, bevacizumab disturbed the morphometric structure at both pressure and tension sites. The histological evaluation indicated about 35-44% fewer osteoblasts in the bevacizumab group, especially at the tension side, whereas the proportion of TRAP-positive osteoclasts at the pressure side was 34-37% higher than the control. The mature Col-I was reduced at the tension site by 33%, whereas the Col-III/Col-I ratio was enhanced by 20-44% at pressure and tension sites, after 2 weeks, in the bevacizumab group. Conclusion: Anti-vascular bevacizumab therapy accentuates OTM in rat model, possibly through the enhancement of bone resorption, at the pressure side, and the reduction of bone formation, at the tension side as well as dysregulation of collagen fibers distribution.

Barbigerone prevents scopolamine-induced memory impairment in rats by inhibiting oxidative stress and acetylcholinesterase levels.

The current study was designed for the evaluation of barbigerone on memory loss. In this experimental study, 24 Wistar rats (n = 6) were used. Control rats and scopolamine (SCOP)-treated control group rats were orally administered with 3 ml of 0.5% sodium carboxymethyl cellulose (vehicle), whereas barbigerone was (10 and 20 mg kg-1) administered orally to the rats from the test group. During the 14-day treatment, control group rats were given 3 ml kg-1 day-1 saline, and all other groups were administered SCOP (1 mg kg-1 day-1, i.p.) 1 h after barbigerone p.o. treatment. The spontaneous alternation activities, learning capacities of a rat's memory were tested with Morris water maze and Y-maze. Reduced glutathione, malondialdehyde, acetylcholine esterase (AChE) and catalase (CAT) levels were measured in rat brain tissue as oxidative stress/antioxidant markers. Moreover, the levels of tumour necrosis factor, interleukin-6 (IL-6) and IL-1ß were also estimated. Treatment with barbigerone in SCOP-administered rats dramatically reduced SCOP-induced neurobehavioural deficits, oxidative stress and neuroinflammatory markers, improved endogenous antioxidants, and restored AChE activity. By improving cholinergic function and reducing oxidative damage, barbigerone could mitigate the effects of SCOP-induced changes in the brain.

Potential of green-synthesized ZnO NPs against human ovarian teratocarcinoma: an in vitro study.

BACKGROUND: Ovarian cancer leads to devastating outcomes, and its treatment is highly challenging. At present, there is a lack of clinical symptoms, well-known sensitivity biomarkers, and patients are diagnosed at an advanced stage. Currently, available therapeutics against ovarian cancer are inefficient, costly, and associated with severe side effects. The present study evaluated the anticancer potential of zinc oxide nanoparticles (ZnO NPs) that were successfully biosynthesized in an ecofriendly mode using pumpkin seed extracts. METHODS AND RESULTS: The anticancer potential of the biosynthesized ZnO NPs was assessed using an in vitro human ovarian teratocarcinoma cell line (PA-1) by well-known assays such as MTT assay, morphological alterations, induction of apoptosis, measurement of reactive oxygen species (ROS) production, and inhibition of cell adhesion/migration. The biogenic ZnO NPs exerted a high level of cytotoxicity against PA-1 cells. Furthermore, the ZnO NPs inhibited cellular adhesion and migration but induced ROS production and cell death through programmed cell death. CONCLUSION: The aforementioned anticancer properties highlight the therapeutic utility of ZnO NPs in ovarian cancer treatment. However, further research is recommended to envisage their mechanism of action in different cancer models and validation in a suitable in vivo system.