Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Bioremoval of tannins and heavy metals using immobilized tannase and biomass of Aspergillus glaucus.

BACKGROUND: The presence of inorganic pollutants and heavy metals in industrial effluents has become a serious threat and environmental issues. Fungi have a remarkable ability to exclude heavy metals from wastewater through biosorption in eco-friendly way. Tannase plays an important role in bioconversion of tannin, a major constituent of tannery effluent, to gallic acid which has great pharmaceutical applications. Therefore, the aim of the current study was to exploit the potential of tannase from Aspergillus glaucus and fungal biomass waste for the bioremediation of heavy metals and tannin. RESULTS: Tannase from A. glaucus was partially purified 4.8-fold by ammonium sulfate precipitation (80%). The enzyme was optimally active at pH 5.0 and 40 °C and stable at this temperature for 1 h. Tannase showed high stability at different physiological conditions, displayed about 50% of its activity at 60 °C and pH range 5.0-6.0. Immobilization of tannase was carried out using methods such. as entrapment in Na-alginate and covalent binding to chitosan. The effects of Na-alginate concentrations on the beads formation and enzyme immobilization revealed that maximum immobilization efficiency (75%) was obtained with 3% Na-alginate. A potential reusability of the immobilized enzyme was showed through keeping 70% of its relative activity up to the fourth cycle. The best bioconversion efficiency of tannic acid to gallic acid by immobilized tannase was at 40 °C with tannic acid concentration up to 50 g/l. Moreover, bioremediation of heavy metal (Cr3+, Pb2+, Cu2+, Fe3+, and Mn2+) from aqueous solution using A. glaucus biomass waste was achieved with uptake percentage of (37.20, 60.30, 55.27, 79.03 and 21.13 respectively). The biomass was successfully used repeatedly for removing Cr3+ after using desorbing agent (0.1 N HCl) for three cycles. CONCLUSION: These results shed the light on the potential use of tannase from locally isolated A. glaucus in the bioremediation of industrial tanneries contained heavy metals and tannin.

Cisplatin-induced bone marrow failure in an adult patient with Fanconi anemia.

INTRODUCTION: Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure typically developing in the first decade of life, congenital abnormalities, and an increased predisposition to malignancy. However, patients with FA can remain undiagnosed until adulthood and present with solid organ malignancies. Due to impaired DNA repair mechanisms, patients with FA are highly susceptible to severe bone marrow toxicity when treated with cisplatin. CASE REPORT: A 38-year-old woman, diagnosed with locally advanced squamous cell carcinoma (SCC) of the uterine cervix, underwent treatment with weekly cisplatin concurrent with radiotherapy. After the second week of cisplatin treatment, she presented with severe pancytopenia. The prolonged and severe pancytopenia following cisplatin and radiation, along with cervical SCC in the absence of risk factors and the presence of parental consanguinity, raised the possibility of FA as the underlying cause. Whole exome sequencing revealed a homozygous FANCI c.668A > C (p.Lys223Thr) missense variant confirming the diagnosis of FA. MANAGEMENT AND OUTCOME: The pancytopenia exhibited a protracted course, necessitating admission and supportive treatment with antibiotics, red blood cell and platelet transfusions, as well as filgrastim and eltrombopag. Eventually, the pancytopenia improved after approximately 40 days of hospitalization. DISCUSSION: SCC of the head and neck or gynecologic organs in a young adult without known risk factors should prompt consideration of FA. Cisplatin should be avoided in patients with FA.

Can digital twin efforts shape microorganism-based alternative food?

With the continuous increment in global population growth, compounded by post-pandemic food security challenges due to labor shortages, effects of climate change, political conflicts, limited land for agriculture, and carbon emissions control, addressing food production in a sustainable manner for future generations is critical. Microorganisms are potential alternative food sources that can help close the gap in food production. For the development of more efficient and yield-enhancing products, it is necessary to have a better understanding on the underlying regulatory molecular pathways of microbial growth. Nevertheless, as microbes are regulated at multiomics scales, current research focusing on single omics (genomics, proteomics, or metabolomics) independently is inadequate for optimizing growth and product output. Here, we discuss digital twin (DT) approaches that integrate systems biology and artificial intelligence in analyzing multiomics datasets to yield a microbial replica model for in silico testing before production. DT models can thus provide a holistic understanding of microbial growth, metabolite biosynthesis mechanisms, as well as identifying crucial production bottlenecks. Our argument, therefore, is to support the development of novel DT models that can potentially revolutionize microorganism-based alternative food production efficiency.

Assessing donor-recipient arterial pressure dynamics in STA-MCA bypass for moyamoya disease.

BACKGROUND: In bypass surgery for moyamoya disease (MMD), the superficial temporal artery's (STA) pressure needs to surpass that of the cortical M4 recipient of the middle cerebral artery (MCA), boosting cerebral blood flow into the MCA and enhancing cerebral circulation. This study investigates the STA-MCA arterial pressure parameters and gradients during bypass surgery, aiming to deepen our understanding of hemodynamic shifts pre- and post-operation. METHODS: DSA imaging data were prospectively collected from patients diagnosed with bilateral MMD who underwent STA-MCA bypass surgery between 2022 and 2023 and stratified according to the Suzuki stage. The mean arterial pressure (MAP) of the donor and recipient arteries was directly measured during the STA-MCA bypass procedure, and these data were statistically analyzed and evaluated. RESULTS: Among 48 MMD patients, Suzuki grading revealed that 43.8% were in early stages (II and III), while 56.2% were in advanced stages (IV, V, and VI). Predominantly, 77.1% presented with ischemic-type MMD and 22.9% with hemorrhagic type. Pre-bypass assessments showed that 62.5% exhibited antegrade blood flow direction, and 37.5% had retrograde. The mean recipient artery pressure was 35.0 ± 2.3 mmHg, with a mean donor-recipient pressure gradient (δP) of 46.4 ± 2.5 mmHg between donor and recipient arteries. Post-bypass, mean recipient artery pressure increased to 73.3 ± 1.6 mmHg. No significant correlation (r = 0.18, P = 0.21) was noted between δP and Suzuki staging. CONCLUSION: Our study elucidated that cerebral blood pressure significantly decreases beyond the moyamoya network at the distal M4 segment. Furthermore, we observed bidirectional flow in MCA territories and a significant positive pressure gradient between the STA and M4 segments. The lack of correlation between Suzuki stages and M4 pressures indicates that angiographic severity may not reflect hemodynamic conditions before surgery, highlighting the need for customized surgical approaches.

The potential role of SNHG16/ miRNA-146a/ TRAF6 signaling pathway in the protective effect of zoledronate against colorectal cancer and associated osteoporosis in mouse model.

Bone fracture as a consequence of colorectal cancer (CRC) and associated osteoporosis (OP) is considered a risk factor for increasing the mortality rate among CRC patients. SNHG16/ miRNA-146a/ TRAF6 signaling pathway is a substantial contributor to neoplastic evolution, progression, and metastasis. Here, we investigated the effect of zoledronate (ZOL) on the growth of CRC and associated OP in a mouse model. Thirty Balb/c mice were divided into Naïve, azoxymethane (AOM)/dextran sodium sulfate (DSS), and ZOL groups. Body weight and small nucleolar RNA host gene 16 (SNHG16) expression, microRNA-146a, and TRAF6 in bone, colon, and stool were investigated. Samples of colon and bone were collected and processed for light microscopic, immunohistochemical staining for cytokeratin 20 (CK20), nuclear protein Ki67 (pKi-67), and caudal type homeobox transcription factor 2 (CDx2) in colon and receptor activator of nuclear factor kB (RANK) and osteoprotegerin (OPG) in bone. A computerized tomography (CT) scan of the femur and tibia was studied. ZOL produced a significant decrease in the expression of SNHG16 and TRAF6 and an increase in miRNA-146a in the colon and bone. ZOL administration improved the histopathological changes in the colon, produced a significant decrease in CK20 and Ki-67, and increased CDx2 expressions. In bone, ZOL prevented osteoporotic changes and tumour cell invasion produced a significant decrease in RANK and an increase in OPG expressions, alongside improved bone mineral density in CT scans. ZOL could be a promising preventive therapy against colitis-induced cancer and associated OP via modulation expression of SNHG16, miRNA-146a, and TRAF6.

Optimization of tannase production by Aspergillus glaucus in solid-state fermentation of black tea waste.

Tannases are valuable industrial enzymes used in food, pharmaceutical, cosmetic, leather manufacture and in environmental biotechnology. In this study, 15 fungal isolates were obtained from Egyptian cultivated soil and marine samples. The isolated fungi were qualitatively and quantitatively screened for their abilities to produce tannase. The selected fungal isolate NRC8 giving highest tannase activity was identified by molecular technique (18S rRNA) as Aspergillus glaucus. Among different tannin-containing wastes tested, the black tea waste was the best substrate for tannase production by Aspergillus glaucus in solid-state fermentation (SSF). Optimization of the different process parameters required for maximum enzyme production was carried out to design a suitable SSF process. Maximal tannase production was achieved with moisture content of 75%, an inoculums size of 6 × 108 spore/ml and sodium nitrate 0.2% (pH of 5.0) at 30 °C after 5 days of incubation. Box-Behnken experiment was designed to get a quadratic model for further optimization studies. Four-factor response-surface method with 27 runs was prepared using independent parameters including (moisture content %, initial pH, substrate concentration (g) and sodium nitrate concentration (g) for tannase model. The F- and P-values of the model were 4.30 and 0.002, respectively, which implied that the model is significant. In addition, the lack-of-fit was 1040.37 which indicates the same significance relative to the pure error. A. glaucus tannase was evaluated by the efficiency of conversion of tannic acid to gallic acid. Moreover, production of gallic acid from SSF process of A. glaucus using black tea waste was found to be 38.27 mg/ml. The best bioconversion efficiency was achieved at 40 °C with tannic acid concentration up to 200 g/L.

Virulence genes contributing to Aeromonas hydrophila pathogenicity in Oreochromis niloticus

Bacterial diseases are the main cause of high economic loss in aquaculture, particularly gram-negative bacteria. This study was conducted for the isolation and identification of Aeromonas and Pseudomonas spp. from diseased fish. Twenty-two Aeromonas and sixteen Pseudomonas isolates were recovered from diseased Nile tilapia (Oreochromis niloticus) raised in eight earthen ponds in Elhox, Metoubes, Kafrelsheikh, Egypt. The recovered isolates were further identified using PCR as 22 Aeromonas hydrophila, 11 Pseudomonas aeruginosa, and 5 Pseudomonas fluorescens isolates. The 22 A. hydrophila isolates were screened for the presence of four virulence genes. Sixteen of the isolates (72.72%) were positive for the aerolysin gene (aer); 4 (18.18%) harbored the cytotoxic enterotoxin gene (act); and 2 (9.09%) carried the hemolysin A gene (hylA) while the cytotonic heat-stable enterotoxin gene (ast) was absent from all the tested isolates. The pathogenicity test indicated the direct relationship between the mortality percentage and the genotype of the tested A. hydrophila isolates as the mortality rates were 63.3 and 73.3% for isolates with two virulence genes (aer+ & act+, and aer+ and hylA+, respectively), followed by 40, 53.3, and 56.6% for isolates with only one virulence gene (hylA, act, and aer, respectively) and 20% for isolates lacking virulence genes. Based on the sensitivity test, the multi-antibiotic resistance profiles were as follows: 90.9% of the A. hydrophila isolates were sensitive to florfenicol and doxycycline; then 68.18% were susceptible to oxytetracycline, norfloxacin, and ciprofloxacin; and 63.63% were susceptible to sulfamethoxazole-trimethoprim, while only 27.27 and 4.5% were sensitive to erythromycin and cephradine, respectively, and all the isolates were resistant to amoxicillin and ampicillin

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