MolDy: molecular dynamics simulation made easy.

MOTIVATION: Molecular dynamics (MD) is a computational experiment that is crucial for understanding the structure of biological macro and micro molecules, their folding, and the inter-molecular interactions. Accurate knowledge of these structural features is the cornerstone in drug development and elucidating macromolecules functions. The open-source GROMACS biomolecular MD simulation program is recognized as a reliable and frequently used simulation program for its precision. However, the user requires expertise, and scripting skills to carrying out MD simulations. RESULTS: We have developed an end-to-end interactive MD simulation application, MolDy for Gromacs. This front-end application provides a customizable user interface integrated with the Python and Perl-based logical backend connecting the Linux shell and Gromacs software. The tool performs analysis and provides the user with simulation trajectories and graphical representations of relevant biophysical parameters. The advantages of MolDy are (i) user-friendly, does not requiring the researcher to have prior knowledge of Linux; (ii) easy installation by a single command; (iii) freely available for academic research; (iv) can run with minimum configuration of operating systems; (v) has valid default prefilled parameters for beginners, and at the same time provides scope for modifications for expert users. AVAILABILITY AND IMPLEMENTATION: MolDy is available freely as compressed source code files with user manual for installation and operation on GitHub: https://github.com/AIBResearchMolDy/Moldyv01.git and on https://aibresearch.com/innovations.

Protective effect of kaempferol glucoside against lipopolysaccharide-caused acute lung injury via targeting Nrf2/NF-κB/NLRP3/GSDMD: Integrating experimental and computational studies.

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1ß (interleukine-1ß) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.

GC-MS Analysis and Microbiological Evaluation of Caraway Essential Oil as a Virulence Attenuating Agent against Pseudomonas aeruginosa.

The emergence of resistant microbes threatens public health on our planet, and the emergence of resistant bacteria against the most commonly used antibiotics necessitates urgent alternative therapeutic options. One way to fight resistant microbes is to design new antimicrobial agents, however, this approach takes decades of research. An alternative or parallel approach is to target the virulence of bacteria with natural or synthetic agents. Active constituents from medicinal plants represent a wide library to screen for natural anti-virulence agents. Caraway is used as a traditional spice and in some medicinal applications such as carminative, antispasmodic, appetizer, and expectorant. Caraway essential oil is rich in terpenes that were previously reported to have antimicrobial activities. In our study, we tested the caraway essential oil in sub-inhibitory concentration as a virulence agent against the Gram-negative bacteria Pseudomonas aeruginosa. Caraway essential oil in sub-inhibitory concentration dramatically blocked protease activity, pyocyanin production, biofilm formation, and quorum sensing activity of P. aeruginosa. The gas chromatography-mass spectroscopy (GC-MS) profile of caraway fruit oil identified 13 compounds representing 85.4% of the total oil components with carvone and sylvestrene as the main constituents. In conclusion, caraway essential oil is a promising virulence-attenuating agent that can be used against topical infections caused by P. aeruginosa.

Correlation of thyroid antibodies with TSH, T3 and T4 hormones in patients diagnosed with autoimmune thyroid disorders.

The serum concentrations of anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies are directly correlate in the induction and diagnosis of autoimmune thyroid disorders (AITDs). Therefore, the evaluation of serum anti-TPO and anti-TG antibodies in relation to thyroid function test parameters including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). This evaluation would be helpful in early diagnosis of abnormal thyroid function and associated autoimmune thyroid diseases. In this cross-sectional study, the serum anti-TPO, anti-TG, T3, T4 and TSH levels of 311 suspected patients of autoimmune thyroid disorders and 40 control subjects were evaluated. The data were presented as mean, ± standard deviations of the mean. Pearson correlation and chi-square tests were used to assess the correlation coefficients and significance in the contingency tables. The thyroid function test parameters in normal and AITDs suspected patients were significantly different in correlation to elevated serum levels of anti-TPO antibody. A significant association was detected between female gender and elevated levels of anti-TPO (P value = 0.047). A higher percentage of women showed elevated levels of anti-TG, but it was not statistically significant (P value= 0.107). The findings of the study reveal a strong correlation between thyroid function test and thyroid antibodies levels, elaborating the clinical importance of thyroid antibodies in clinical examination and follow-up of patients with autoimmune thyroid disorders.

Acute paraplegia caused by Schistosoma mansoni.

Schistosomiasis affects over 200 million people worldwide. Involvement of the CNS is a rare occurrence. We report 2 young males who presented with rapidly progressing paraparesis associated with urinary incontinence. In both cases, MRI of the spine demonstrated a diffusely enhancing mass at the conus medullaris with extensive spinal cord edema. Laboratory investigations revealed mild peripheral eosinophilia and abnormal, but non-specific, CSF analysis. In one patient, the diagnosis was made based on a rising schistosomal titer with a positive rectal biopsy. In the other patient, spinal cord biopsy revealed a granuloma. Both cases were caused by Schistosoma mansoni and patients were treated with praziquantel and steroid therapy. They both made a remarkable neurological recovery. We emphasize that a high index of suspicion should be raised in the differential diagnosis of transverse myelitis in endemic areas.

Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

Synergistic Activity of 3-Hydrazinoquinoxaline-2-Thiol in Combination with Penicillin Against MRSA.

Background: The growing resistance seen in various antibiotics, including those considered as last-resort options, underscores the pressing need for novel approaches and new substances to address MRSA infections. Combining antibiotics as a treatment approach can enhance effectiveness, expand the range of targeted bacteria, and minimize the likelihood of resistance emergence. This approach holds promise in addressing the escalating issue of antibiotic resistance. Purpose: This study seeks to investigate the potential synergy between 3-hydrazinoquinoxaline-2-thiol and penicillin against a diverse array of MRSA isolates, thereby providing insights into their combined antimicrobial action. Methods: Twenty-two clinical MRSA isolates subjected to broth microdilution to determine the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and penicillin. Subsequently, a checkerboard assay was employed to evaluate the interaction between 3-hydrazinoquinoxaline-2-thiol and penicillin, focusing on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of penicillin and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical MRSA strains. Penicillin exhibited MICs within a range of 1024 to 128 µg/mL, while 3-hydrazinoquinoxaline-2-thiol displayed MICs varying from 64 to 8 µg/mL. Remarkably, the combination of 3-hydrazinoquinoxaline-2-thiol and penicillin yielded a synergistic effect, resulting in a significant reduction of MICs by up to 64-fold. Conclusion: The potential of 3-hydrazinoquinoxaline-2-thiol in combination with penicillin as a viable solution against MRSA appears promising. However, to establish its practical utility, further extensive testing and experiments are essential.

RETRACTED: Alhakamy et al. Development and Optimization of Luliconazole Spanlastics to Augment the Antifungal Activity against Candida albicans. Pharmaceutics 2021, 13, 977.

The journal retracts the article, "Development and Optimization of Luliconazole Spanlastics to Augment the Antifungal Activity against Candida albicans" [...].

RETRACTED: Fahmy et al. Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation. Pharmaceutics 2020, 12, 485.

This journal retracts the article "Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation" [...].

Thymoquinone is a natural antibiofilm and pathogenicity attenuating agent in Pseudomonas aeruginosa.

Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due to their high rate of resistance as listed by WHO. P. aeruginosa can result in many nosocomial infections especially in individuals with compromised immune systems. Attenuating virulence factors by interference with quorum sensing (QS) systems is a promising approach to treat P. aeruginosa-resistant infections. Thymoquinone is a natural compound isolated from Nigella sativa (black seed) essential oil. In this study, the minimum inhibitory concentration of thymoquinone was detected followed by investigating the antibiofilm and antivirulence activities of the subinhibitory concentration of thymoquinone against P. aeruginosa PAO1. The effect of thymoquinone on the expression of QS genes was assessed by quantitative real-time PCR, and the protective effect of thymoquinone against the pathogenesis of PAO1 in mice was detected by the mouse survival test. Thymoquinone significantly inhibited biofilm, pyocyanin, protease activity, and swarming motility. At the molecular level, thymoquinone markedly downregulated QS genes lasI, lasR, rhlI, and rhlR. Moreover, thymoquinone could protect mice from the pathologic effects of P. aeruginosa increasing mouse survival from 20% to 100%. In conclusion, thymoquinone is a promising natural agent that can be used as an adjunct therapeutic agent with antibiotics to attenuate the pathogenicity of P. aeruginosa.

The Combination of 3-Hydrazinoquinoxaline-2-Thiol with Thymoquinone Demonstrates Synergistic Activity Against Different Candida Strains.

Introduction: Candida is the primary cause of invasive fungal disease, candidiasis, especially in developed nations. The increasing resistance observed in multiple antibiotics, coupled with the prolonged process of creating new antibiotics from the ground up, emphasizes the urgent requirement for innovative methods and new compounds to combat Candida infections. Employing a treatment strategy that combines antibiotics can improve efficacy, broaden the spectrum of targeted fungal, and reduce the chances of resistance emergence. This approach shows potential in tackling the escalating problem of antibiotic resistance. The objective of this research is to explore the potential synergistic effects of combining 3-hydrazinoquinoxaline-2-thiol and thymoquinone against a variety of Candida isolates. This investigation aims to offer an understanding of the collective antimicrobial action of these compounds. Methods: Broth microdilution was utilized to assess the Minimum Inhibitory Concentrations (MICs) of 3-hydrazinoquinoxaline-2-thiol and thymoquinone for 22 clinical Candida isolates. Following this, a checkerboard assay was employed to analyze the interaction between 3-hydrazinoquinoxaline-2-thiol and thymoquinone, with a specific focus on the Fractional Inhibitory Concentration Index (FICI). Results: The MICs of thymoquinone and 3-hydrazinoquinoxaline-2-thiol were determined for 22 clinical Candida strains, with thymoquinone exhibiting MICs ranging from 64 to 8 µg/mL, and 3-hydrazinoquinoxaline-2-thiol displaying MICs varying from 64 to 8 µg/mL. Notably, the combination of 3-hydrazinoquinoxaline-2-thiol and thymoquinone resulted in a synergistic effect, leading to a significant reduction in MICs, with reductions of up to 64-fold with FICI below 0.5 against tested strains. Conclusion: The prospect of using 3-hydrazinoquinoxaline-2-thiol in combination with thymoquinone as an effective solution against Candida looks encouraging. Nevertheless, to validate its practical applicability, additional comprehensive testing and experiments are imperative.

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice.

Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1ß, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1ß/iNOS signaling pathways.

The Prevalence and Risk Factors of Trichosporonosis at King Abdulaziz University Hospital.

Background: Fungal infections, especially those caused have emerged as a significant medical concern over the past three decades, particularly among immunocompromised patients. However, recent studies have highlighted the increasing prevalence of fungal infections resembling yeast other than Candida, such as trichosporonosis, especially among immunosuppressed individuals worldwide. Trichosporon has been identified as a significant contributor to superficial and invasive infections. Invasive trichosporonosis, primarily affecting immunocompromised patients, poses a significant threat with high mortality rates. Purpose: The current study aimed to explore the clinical epidemiology of Trichosporon spp at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. Methods: This retrospective study aimed to assess the clinical epidemiology of Trichosporon spp. infections in microbiology cultures obtained from KAUH in Saudi Arabia. The study analyzed data from patients over a five-year period, focusing on demographic, clinical, and microbiological characteristics. Results: This study encompassed 21 participants, categorized into four distinct age groups. Moreover, this study indicated T. asahii as the predominant species isolated, accounting for 90.5% of infections, followed by T. mucoides (9.5%). ICU hospitalization, diabetes mellitus, taking immunosuppressive drugs, and antifungal drugs, and the use of invasive medical equipment were identified as prominent risk factors for trichosporonosis. Urinary tract infections were the most common clinical presentation, particularly among male and elderly patients. Mortality rates were high, especially among older individuals. Conclusion: This study contributes valuable epidemiological insights into trichosporonosis, highlighting the need for enhanced surveillance and preventive strategies in healthcare settings. Further research is warranted to optimize treatment approaches and infection control measures, ultimately reducing the burden of Trichosporon infections on patient outcomes.

RETRACTED: Awan et al. The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells. Pharmaceutics 2020, 12, 597.

The journal retracts the article, "The Enhanced Cytotoxic and Pro-Apoptotic Effects of Optimized Simvastatin-Loaded Emulsomes on MCF-7 Breast Cancer Cells" [...].

Prevalence of wheat allergy in Al-Kharj, Saudi Arabia.

BACKGROUND: Wheat allergy has been suggested to represent an important allergic disease. This study collates clinical and laboratory aspects in patients with wheat allergy in Al-Kharj city, Saudi Arabia. METHODS: Total and specific IgE were measured in 15 suspected cases of wheat allergy. Protein allergenicity was assessed with Western blotting. RESULTS: Significant elevation of total and specific IgE was found in 4 cases. Basophlia was also demonstrated on blood film. Western blotting results showed 2 bands (83 and 40 kDa). CONCLUSION: Wheat allergy must also be considered when planning treatment of asthma and eczema of adult patients.

Animal allergy among husbandry personnel in Riyadh.

BACKGROUND: The importance of specific animal allergy in immunopathology of asthma and atopic diseases remained to be defined. METHODS: We measured total and specific IgE. Western blotting of some allergens was also characterised. RESULT: There was a significant elevation of IgE in 3 persons among 15 samples collected. Western blotting showed common husbandry allergens from 3 sources that have common allergenicity. CONCLUSION: Exposure to animal products exacerbates allergic asthma in adults, suggesting that preventive measures should be taken to reduce their sensitivity.

Posterior fossa teratoma.

Germ cell tumors comprise approximately 2-5% of all childhood brain tumors. They arise predominantly in the pineal and suprasellar region, but may occur throughout the brain. Teratomas are generally divided into gonadal and extragonadal types. A posterior fossa teratoma is a rare occurrence. The focus of this discussion is a 5-year-old boy with posterior fossa teratoma who recovered completely after medical and surgical intervention. We also present his interesting imaging and pathological findings.

Reversible Parkinsonism caused by deep cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is an uncommon but serious disorder with highly variable clinical presentation. Over the past decade, more cases of CVST have been diagnosed more frequently and at an early stage of the disease process. This is mainly attributed to increased awareness by neurologists and the availability of sensitive non-invasive neuro-imaging techniques. Cerebral venous sinus thrombosis often affects children, adolescents, and young adults with female preponderance. We report a case of Parkinsonism secondary to deep CVST (DCVST), which recovered completely following treatment. Recognition of DCVST as a cause for Parkinsonism is of paramount importance due to its reversibility and favorable outcome when appropriately managed.

Antenatal Screening for Toxoplasmosis and Rubella in Saudi Arabia: Assessing the Need for Screening.

Objective: Antenatal screening programs are highly recommended to limit maternal and neonatal infections such as toxoplasmosis and rubella. This study aimed to assess the seroprevalence of maternal toxoplasma and rubella among pregnant women tested during antenatal screening at the King Abdulaziz University Hospital, Saudi Arabia. Methods: This descriptive cross-sectional study targeted pregnant women attending the King Abdulaziz University Hospital, Jeddah, Saudi Arabia, during the period of 2019-2022 for antenatal follow-up. This study included 3653 pregnant women who attended an antenatal screening. The clinical consequences of pregnancy were evaluated and categorized into six main categories based on the related complications and comorbidities of the pregnant women. The data were analyzed using the SPSS program as a descriptive statistic, and an ANOVA was used to test the associations. Results: The study findings showed that 12% of women were seropositive for toxoplasmosis and 71.4% were seropositive for rubella, and it found that almost all women (except two) were seronegative for Toxo IgM (immunoglobulin M) and rubella IgM, which indicates the absence of recent infections during the pregnancy. Approximately 19% and 4% of women who had no comorbidities experienced complicated pregnancies and delivery, respectively. Moreover, 1.3% of the pregnant women had comorbidities, complicated pregnancies, and problems during delivery. The mean Toxo IgG level was significantly higher in women with normal pregnancies than in those with other pregnancies. Rubella immunoglobulin levels did not significantly correlate with pregnancy or delivery problems. Conclusion: The seropositivity prevalence of toxoplasma Ig M and rubella Ig M were very low at the King Abdulaziz University Hospital, Saudi Arabia, indicating absence of current infections. However, the benefits of routine antenatal screening in pregnant women remain unclear. This study was conducted at one hospital, with a limited sample of participants, and did not yield adequate evidence to recommend a broader implementation of antenatal testing for toxoplasmosis and rubella.

Archimedes Optimization Algorithm with Deep Learning-Based Prostate Cancer Classification on Magnetic Resonance Imaging.

Prostate cancer (PCa) is becoming one of the most frequently occurring cancers among men and causes an even greater number of deaths. Due to the complexity of tumor masses, radiologists find it difficult to identify PCa accurately. Over the years, several PCa-detecting methods have been formulated, but these methods cannot identify cancer efficiently. Artificial Intelligence (AI) has both information technologies that simulate natural or biological phenomena and human intelligence in addressing issues. AI technologies have been broadly implemented in the healthcare domain, including 3D printing, disease diagnosis, health monitoring, hospital scheduling, clinical decision support, classification and prediction, and medical data analysis. These applications significantly boost the cost-effectiveness and accuracy of healthcare services. This article introduces an Archimedes Optimization Algorithm with Deep Learning-based Prostate Cancer Classification (AOADLB-P2C) model on MRI images. The presented AOADLB-P2C model examines MRI images for the identification of PCa. To accomplish this, the AOADLB-P2C model performs pre-processing in two stages: adaptive median filtering (AMF)-based noise removal and contrast enhancement. Additionally, the presented AOADLB-P2C model extracts features via a densely connected network (DenseNet-161) model with a root-mean-square propagation (RMSProp) optimizer. Finally, the presented AOADLB-P2C model classifies PCa using the AOA with a least-squares support vector machine (LS-SVM) method. The simulation values of the presented AOADLB-P2C model are tested using a benchmark MRI dataset. The comparative experimental results demonstrate the improvements of the AOADLB-P2C model over other recent approaches.