Identifying the specific-targeted marine cerebrosides against SARS-CoV-2: an integrated computational approach

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products. So far, 167 cerebrosides, compounds 1–167, have been isolated from diverse marine organisms or microorganisms. The as yet smaller number of compounds that have been studied more in depth proves a potential against challenging diseases, such as cancer, a range of viral and bacterial diseases, as well as inflammation. This review provides a comprehensive summary on this so far under-explored class of compounds, their chemical structures, bioactivities, and their marine sources, with a full coverage to the end of 2020. Today, the global pandemic concern, COVID-19, has claimed millions of death cases around the world, making the development of anti-SARS-CoV-2 drugs urgently needed for such a battle. Accordingly, selected examples from all subclasses of cerebrosides were virtually screened for potential inhibition of SARS-CoV-2 proteins that are crucially involved in the viral–host interaction, viral replication, or in disease progression. The results highlight five cerebrosides that could preferentially bind to the hACE2 protein, with binding scores between −7.1 and −7.6 kcal mol⁻¹ and with the docking poses determined underneath the first α₁-helix of the protein. Moreover, the molecular interaction determined by molecular dynamic (MD) simulation revealed that renieroside C1 (60) is more conveniently involved in key hydrophobic interactions with the best stability, least deviation, least ΔG (−6.9 kcal mol⁻¹) and an RMSD value of 3.6 Å. Thus, the structural insights assure better binding affinity and favorable molecular interaction of renieroside C1 (60) towards the hACE2 protein, which plays a crucial role in the biology and pathogenesis of SARS-CoV-2.

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products.     

Paper-based potentiometric sensing devices modified with chemically reduced graphene oxide (CRGO) for trace level determination of pholcodine (opiate derivative drug)

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized. A printed pholcodinium (PHL)²⁺/5-nitrobarbiturate (NB)⁻ ion-association complex as a sensory material-based all-solid-state ion-selective electrode (ISE) on a chemically reduced graphene oxide (CRGO) solid-contact, and a printed all-solid-state Ag/AgCl reference electrode, has been combined on a hydrophobic paper substrate coated with fluorinated alkyl silane (CF₃(CF₂)₇CH₂CH₂SiCl₃, C^F₁₀). The sensors revealed a potentiometric slope of 28.7 ± 0.3 mV dec⁻¹ (R² = 0.9998) over a linear range starting from 2.0 × 10⁻⁷ M to 1.0 × 10⁻² M and a detection limit of 0.04 μg mL⁻¹. The repeatability and stability of the pholcodine paper-based sensor was found to be 2.32%. The RSD% (n = 6) was found to be 2.67% when using five different paper-based sensors. The sensor revealed an excellent selectivity towards PHL over dextromethorphan, codeine, ephedrine, carbinoxamine, caffeine, ketamine, and K⁺, Na⁺ and Ca²⁺ ions. It showed a good recovery (94–104%) for the determination of PHL in different artificial serum samples. The presented paper-based analytical device was successfully introduced for PHL determination in different pharmaceutical formulations (i.e. syrups and suspensions) containing pholcodine. The current work can be considered as a promising possible analytical tool to obtain cost-effective and disposable paper-based potentiometric sensing devices. These devices can be potentially manufacturable at large scales in pharmaceutical, clinical and forensic applications for opiate drug assessment.

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized.     

Locally advanced tongue squamous cell carcinoma in epidermolysis simplex bullosa patient: a therapeutic conundrum

Epidermolysis bullosa simplex (EBS) is a debilitating condition affecting the skin and mucous membranes that is characterised by frequent ulceration and blistering on trivial trauma. In EBS, oral cavity mucosal injuries lead to a high propensity for developing squamous cell carcinomas. Locally advanced tongue carcinoma arising in this background presents a challenging therapeutic conundrum. To our knowledge, this is the first case of aggressive locally advanced tongue carcinoma that has developed sporadically in a patient with EBS and no family history. Routine screening of oral mucosal lesions will lead to early detection and timely management of this debilitating condition.     

Intralesional zinc sulfate 2% vs intralesional vitamin D in plantar warts: A clinicodermoscopic study

Verrucae are benign proliferations seen in skin due to infection with papillomaviruses. There are different treatment strategies for warts but all of these treatments are painful, time consuming, expensive, and recurrence is common. To evaluate and compare the efficacy of intralesional 2% zinc sulfate solution vs vitamin D3 in the treatment of plantar warts, as well as reporting the side effects. This three‐armed randomized clinical trial included 105 patients presented with plantar warts divided into three groups, 35 patients per group. The first group received intralesional 2% zinc sulfate, the second group received intralesional 2% vitamin D3, and the third group received normal saline. Four sessions were done, one every 2 weeks. At the end of the study, patients showing complete response were more in zinc group (71.4%), vitamin D3 group (62.9%) compared to saline group (40%). Most of the patients in zinc group showed severe pain during injection (48.6%), most of the patients in vitamin D3 group showed mild pain (80%), while most of the patients in saline group showed no pain (57.1%). Both intralesional 2% zinc sulfate and vitamin D3 are effective in treatment of plantar warts, with zinc sulfate being more effective.     

Molecular miR-19a in Acute Myocardial Infarction: Novel Potential Indicators of Prognosis and Early Diagnosis

Objective: Due to the increasing annual incidence rate of disability and mortality in patients with acute myocardial infarction (AMI), the need for an appropriate diagnostic tool has become a crucial urgent issue. An increase in biomarkers and protein levels in response to AMI can be used as a predictive biomarker with different sensitivities and specificities. This study aimed at investigating the role of miR-19a as a biomarker with acceptable sensitivity and specificity for early diagnosis of AMI. Methods: We studied 175 patients with AMI admitted within 12 h of symptom onset and 90 healthy subjects as control group. Patients were divided into two groups, including group I (normal vessels and no significant artery stenosis) and primary percutaneous coronary intervention (PCI) group II (patients with more than 50% stenosis in vessels and severe atherosclerosis) diagnosed by angiography. The expression level of miR-19a was evaluated by the real-time polymerase chain reaction and other serum chemistries were also analyzed. Results: The results demonstrated that circulating miR-19a levels were significantly increased in patient groups compared to the control group (2.88 ± 1.06 vs. 5.93 ± 1.28, P<0.0001). We also found that miR-19a levels were higher in group II (134.62-fold) than group I (15.42-fold). The upper levels of miR-19a were significantly correlated with the increased serum levels of CK-MB (ρ=0.29, P<0.0001), CTn I (ρ=0.4, P<0.0001) and creatinine (ρ=0.27, P<0.0001). In addition, Receiver Operating Characteristic (ROC) analysis revealed that circulating miR-19a had considerable diagnostic accuracy for the patients with normal vessel with an AUC of 0.930 (95% CI: 0.697-0.765) and for PCI patients with an AUC of 0.966 (95% CI: 0.748-0.784). Conclusion: Circulating miR-19a possibly has prognostic value to be used as a promising molecular target for early diagnosis and prognosis of AMI.     

A sleep schedule incorporating naps benefits the transformation of hierarchical knowledge

Study ObjectivesThe learning brain establishes schemas (knowledge structures) that benefit subsequent learning. We investigated how sleep and having a schema might benefit initial learning followed by rearranged and expanded memoranda. We concurrently examined the contributions of sleep spindles and slow-wave sleep to learning outcomes.MethodsFifty-three adolescents were randomly assigned to an 8 h Nap schedule (6.5 h nocturnal sleep with a 90-minute daytime nap) or an 8 h No-Nap, nocturnal-only sleep schedule. The study spanned 14 nights, simulating successive school weeks. We utilized a transitive inference task involving hierarchically ordered faces. Initial learning to set up the schema was followed by rearrangement of the hierarchy (accommodation) and hierarchy expansion (assimilation). The expanded sequence was restudied. Recall of hierarchical knowledge was tested after initial learning and at multiple points for all subsequent phases. As a control, both groups underwent a No-schema condition where the hierarchy was introduced and modified without opportunity to set up a schema. Electroencephalography accompanied the multiple sleep opportunities.ResultsThere were main effects of Nap schedule and Schema condition evidenced by superior recall of initial learning, reordered and expanded memoranda. Improved recall was consistently associated with higher fast spindle density but not slow-wave measures. This was true for both nocturnal sleep and daytime naps.ConclusionA sleep schedule incorporating regular nap opportunities compared to one that only had nocturnal sleep benefited building of robust and flexible schemas, facilitating recall of the subsequently rearranged and expanded structured knowledge. These benefits appear to be strongly associated with fast spindles.Clinical Trial registration{"type":"clinical-trial","attrs":{"text":"NCT04044885","term_id":"NCT04044885"}}NCT04044885 (https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT04044885","term_id":"NCT04044885"}}NCT04044885).     

A simple single jar “on–off fluorescence” designed system for the determination of mitoxantrone using an eosin Y dye in raw powder,vial, and human biofluids

In this work, a direct, simple, one-pot, and green spectrofluorimetric approach was applied to measure mitoxantrone, a chemotherapeutic agent, through a green validated method. The suggested approach focused on establishing an easy association complex combining mitoxantrone and the eosin Y reagent in a slightly acidic solution. The fluorometric analysis was dependent on off-mitoxantrone action on the emission intensity of the dye (eosin Y) at 544.5 nm (excitation = 301 nm). The devised system has a linear range of 0.07–2.5 μg mL⁻¹ and a detection limit of 0.016 μg mL⁻¹. All system parameters for the formation of mitoxantrone–eosin Y complexes were modulated analytically. Also, the system was reviewed in agreement with ICH criteria. Furthermore, the proposed model was approached to quantify mitoxantrone in its pharmaceutical vial dosage form with high recoveries. Also, the proposed spectroscopic design was efficiently employed to detect the investigated drug in body fluids (blood and urine). Lastly, the designed method was evaluated from a greenness point of view according to eco-scale.

This work describes a green fluorescence on–off system that relies on establishing a simple ion association complex pairing the mitoxantrone antineoplastic drug with the eosin Y reagent in a slightly acidic solution.     

A customized metal guide for controllable modification of anterior teeth contour prior to minimally invasive preparation

ObjectiveOptimal tooth reduction is a key requirement for aesthetics, function, and the longevity of fixed restorations. Research has demonstrated that controlled and conservative tooth preparation is crucial for the long-term success of adhesive restorations. Different techniques of fabricating reduction guides have been previously reported in literature. The present technical note describes the fabrication technique and clinical application of a customized metal preparation reduction guide.Material and methodPatient presented with tilted maxillary left central incisor. The flared-out part of the tooth was modified prior to veneer restoration preparation. Resin pattern reduction guide was fabricated on the diagnostic cast with a window on the tilted mesial portion of the tooth. After intraoral evaluation, resin pattern guide was casted. Metal reduction guide was place intraorally and reduction was provided on the exposed surface of the tooth. After the removal of the tilted portion, a harmonious arch form allowed the clinician to provide adequate evaluation and preparation for veneer restorations.ResultsThe device demonstrated good practical value, allowing for selective and controlled reduction of tooth structure, and definitive protection of adjacent tooth surfaces from iatrogenic damage. The clinical outcome successfully addressed the patient’s restorative and aesthetic needs, and the veneer was stable 2 years postoperatively.ConclusionUse of a metal guide assists clinicians to provide a more predictable reduction of a desired tooth surface, while decreasing the risk of compromising the other/adjacent tooth surfaces.