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Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.
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Objectives: The objective is to develop a low-cost, practical, portable aptasensor platform for the diagnosis of COVID-19. Materials -Methods: Amino-terminated aptamers to be used for the design of an aptasensor were synthesized by SELEX method, and interaction of aptamers with SARS-CoV-2 S1 protein was investigated by isothermal titration calorimetry (ITC). Gold electrodes were used to design the biosensor platform. After the electrode surface was functionalized with cysteamine, the amino-terminated aptamer was conjugated to the surface via glutaraldehyde crosslinker. Then, the surface characterization and analytical parameters of the designed sensing platform were determined by adding commercial S1 proteins on the surface using differential pulse voltammetry (DPV), cyclic voltammetry (CV) and impedance spectroscopy (EIS). To evaluate the working performance of the system, S1 proteins were added to the synthetic serum samples using the standard addition method and the measurements were repeated. Result(s): Surface characterization of the platform designed with EIS and CV measurements was performed and it was found that the modification was successfully performed. In addition, DPV results and analytical parameters of the platform (calibration plot, limit of detection(LOD) , repeatability, coefficient of variation) were determined and the working performance of system was evaluated. Moreover, working performance of the biosensor in real samples and its specificity for COVID -19 were determined by experiments with synthetic serum and influenza A and B proteins. Conclusion(s): According the results, the system has potential to be used for the detection of COVID -19, and also it can be rapidly adapted in different pandemic situations that may occur in the future.
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SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical tools such as SEC chromatography, dynamics light scattering, fluorescence binding assays, and electron microscopy, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV-1, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
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Case report Background: Delayed hypersensitivity reactions to hyaluronic acid fillers are usually self-limiting and uncommon, and spontaneous resolution is frequent. These are presumably T-lymphocyte- mediated reactions that can be caused by flu-like infections and vaccinations. A delayed hypersensitivity reaction after hyaluronic acid filler following the mRNA vaccine against coronavirus has already been described in the literature. We wish to present a case that followed the ChAdOx1-s recombinant COVID-19 vaccine produced by Oxford/ AstraZeneca. Case report: Female patient, 61 years old, submitted to filling of the nasojugal sulcus and nasolabial fold with 1 ml of cross-linked hyaluronic acid -15 mg/ml and after 5 days filling in the lips with 1 ml of cross-linked hyaluronic acid -12 mg/ml, dermatological office, under aseptic technique and using cannulas. It evolved with ecchymosis on the lips and nasolabial folds, with spontaneous resolution after about a week. Sixteen weeks after the procedure, she received the first dose of the ChAdOx1-s recombinant COVID-19 vaccine, and 11 weeks later, the second dose. After 30 days of the 2nd vaccine dose, asymptomatic nodules appeared distributed in the upper and lower portions of nasolabial folds, in melomentonian grooves, in the supralabial region, in the upper and lower lip in the right and left lateral portions and in the infralabial region in the left lateral portion, coinciding with the topographies of the populated areas. Ultrasonographic evaluation with Doppler confirmed these findings. At the time, she denied fever or previous infectious signs or symptoms. Previously, the patient had already been submitted to the filling of the nasojugal and nasolabial folds with a hyaluronic acid-based filler (1 ml), 29 months before the current procedure, without intercurrences. After the appearance of the nodules, she underwent treatment with prednisone 40mg for 15 days, with total weaning after another 15 days, in addition to the use of levoceritizine 5 mg daily for 20 days, with partial reduction in the size of the nodules. Due to aesthetic complaints on the part of the patient, an intralesional injection of hyaluronidase was scheduled, but it was not performed at the request of the patient herself, who opted for expectant management and clinical treatment. In October 2021, the patient reported that the nodules had involuted and in December 2021 she remained asymptomatic, referring to resorption of the entire filler.
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Violations of the hemostasis (blood aggregation control, BAC) system in patients with COVID-19 in the acute period and at the stage of convalescence have been studied and methods of targeted correction of the identified disorders are considered. Prevention of serious complications related to COVID-19 infection requires complex assessment of the hemostasis system and prompt correction of disorders. Methods of clinical hemostasiograms and low-frequency piezothromboelastography (LPTEG) provide comprehensive and informative assessment of functional state of the BAC system and monitoring of the effectiveness of therapy, both in hospital and on outpatient basis. It was established that hemostasis system disorders had unspecified character with hyper- or hypocoagulation in the acute period and structural or chronometric hypercoagulation in the recovery period. Under LPTEG monitoring in hospital, the identified disorders were corrected by low-molecular-weight (LMW) heparins, blood-based preparations, and fibrinolysis inhibitors;at the outpatient stage, the therapy was supplemented with sulodexide and anticoagulants. Personalized correction of the hemostatic potential was based on the following LPTEG parameters. Prescription of the anti-aggregant and vasoprotective therapy required that the response time (t1) would be reduced below 0.9 min and thrombin activity (TA) constant increased above 40 relative units. The anticoagulant therapy was prescribed when the gelation point (t3) decreased to 4.7 min and the coagulation drive intensity (CDI) index was above 50 relative units. The fibrinolytic activity was corrected when the clot polymerization intensity (CPI) index was above 20 relative units, the cross-linked fibrin formation time (t5) decreased to 27 min, and the clot retraction and lysis intensity (CRLI) index exceeded 15%. The boundary values of these LPTEG parameters were adjusted at the levels of moderate hypercoagulation or reference normal coagulation. The LPTEG monitoring and personalization of the prescribed antithrombotic therapy allowed the risk of thrombo-hemorrhagic complications to be reduced at all stages of COVID-19 treatment.Copyright © 2021 Authors. All rights reserved.
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Background: Coronavirus disease-19 (COVID-19) is an infectious disease that can result in serious respiratory illness. It is associated with extensive systemic inflammation and changes to the lung extracellular matrix (ECM), which may result in diffuse alveolar damage and pulmonary fibrosis. In this study, the aim was to investigate whether ECM remodeling, wound healing, and neutrophil activity is altered in patients with COVID-19, with or without interstitial lung disease (ILD). Method(s): Serum was collected from 72 patients with COVID-19 infection 3 months after diagnosis, 10 of whom developed ILD, and from 16 healthy controls. A panel of neo-epitope specific ELISAs reflecting type III collagen crosslinking (PC3X), type III and VI collagen formation (PRO-C3 and PRO-C6), type I, III, and VI collagen degradation (C1M, C3M, and C6M), fibrin crosslinking (X-FIB), fibrin clot formation (PRO-FIB), elastin degradation (EL-NE and ELP-3), and calprotectin degradation (CPa9-HNE) were assessed in serum of patients. Result(s): Mean serum neo-epitopes PC3X (p<0.0001), PRO-C3 (p=0.0024), C3M (p=0.0085), PRO-FIB (p<0.0001), ELP-3 (p<0.0001), and CPa9-HNE (p<0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Additionally, PC3X (p=0.023) and PRO-C3 (p=0.0317) were significantly elevated in COVID-19 patients who developed ILD when compared to those who did not. Conclusion(s): Non-invasive serological biomarkers reflecting tissue remodeling were significantly elevated in patients infected with COVID-19. Additionally, type III collagen crosslinking and formation may differentiate patients who develop ILD consequent to COVID-19 infection.
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Rationale: The COVID-19 pandemic has led to the deaths of millions with its ability to cause severe pneumonia. Diagnosis is based on PCR testing which has many limitations: lengthy turnaround times, lack of universal availability and variance in sensitivity. Imaging such as CXR could be a valuable and faster aid in diagnosing COVID-19 compared to PCR. It is widely available, cheap and can be performed at the bedside- enabling a rapid turnover of patients whilst minimising cross-link infection. However only a few studies have assessed its prognostic value. We aim to analyse the diagnostic accuracy of CXR in COVID-19 and to assess if severity of COVID pneumonitis on CXR correlated with mortality. Method(s): A retrospective study of all in-patients aged >= 18 years with a confirmed diagnosis of COVID-19 during the first and second waves of the pandemic. Admission CXRs and in-patient CT Thorax scans were analysed. Statistical analysis was performed using the Chi-Squared Test for independence. Result(s): 999 COVID-19 patients were included in the study. Severity of COVID pneumonitis on CXR correlated with mortality when patients were grouped into the following categories: normal (n=161, mortality=42%), mild (n=220,mortality=33%) moderate, (n=328, mortality=42%) and severe (n=290, mortality=58%) (P<0.001). 251 patients had both CT and CXRs. CT scans were superior in diagnosing COVID pneumonitis (63%) compared to CXR (47%) (P<0.001). Conclusion(s): Our study showed a positive correlation between the severity of COVID pneumonitis on CXR and mortality, supporting the use of CXR in the ED to help rapidly identify and treat patients at high risk of death.
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Recent years have been associated with the development of various sensor-based technologies in response to the undeniable need for the rapid and precise analysis of an immense variety of pharmaceuticals. In this regard, special attention has been paid to the design and fabrication of sensing platforms based on electrochemical detection methods as they can offer many advantages, such as portability, ease of use, relatively cheap instruments, and fast response times. Carbon paste electrodes (CPEs) are among the most promising conductive electrodes due to their beneficial properties, including ease of electrode modification, facile surface renewability, low background currents, and the ability to modify with different analytes. However, their widespread use is affected by the lack of sufficient selectivity of CPEs. Molecularly imprinted polymers (MIPs) composed of tailor-made cavities for specific target molecules are appealing complementary additives that can overcome this limitation. Accordingly, adding MIP to the carbon paste matrix can contribute to the required selectivity of sensing platforms. This review aims to present a categorized report on the recent research and the outcomes in the combinatory fields of MIPs and CPEs for determining pharmaceuticals in complex and simple matrices. CPEs modified with MIPs of various pharmaceutical compounds, including analgesic drugs, antibiotics, antivirals, cardiovascular drugs, as well as therapeutic agents affecting the central nervous system (CNS), will be addressed in detail.Copyright © 2023 Elsevier B.V.
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Background: FarmaFlux is a non-profit organisation providing e-health services to community pharmacists in Belgium. When the pandemic struck a new service was launched to collect relevant data to tackle strategic issues with regard to the COVID-19 crisis. Purpose(s): The COVID-19 Monitor was launched to detect pharmacy activity and drop out. Dispensing volume of relevant medicines was monitored to be able to prevent shortages. Afterwards they were used for outbreak detection and follow up of adherence. Method(s): Professional associations of community pharmacists participated in the national task force 'Shortages' and collected data about dispensing volumes of relevant medicines. Pharmacy activity data were provided at province level. Dispensing data were cross linked with medical data, mobility indicators, financial transactions and absenteeism during the exit phase. Volumes of metformin dispensing were used as an indicator for follow up of chronic treatment. Result(s): Community pharmacy drop out rose up to 3% in early April;but dropped afterwards and gradually went back to normal. Shortages of midazolam and oxygen were the most critical in ambulatory care. They were mitigated by the national task force. Dispensing data were shared with and processed by the federal scientific institution Sciensano. Results of the analysis were shared with the Group of Experts for the Exit Strategy (GEES). Metformin showed a stock piling peak the days before lockdown and an important drop afterwards. Conclusion(s): Dispensing data, collected by FarmaFlux, provided useful information to detect: community pharmacy drop out, medicines shortages in ambulatory care, follow up of adherence and early outbreak detection during the COVID19 crisis.
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Microsponges are extremely cross-linked, non-collapsible, porous, polymeric microspheres having particle size range from 5 to 300 mum. They are highly effective, stable, non-irritant, nontoxic, non-allergic, non-mutagenic and also minimum side effects with improved patient compliance. Ivermectin is act as an antiparasitic agent and antiviral agent, shows an inhibitory effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in primary stage. Ivermectin microsponges is prepared by quasi emulsion-solvent diffusion method by using two polymers in different proportion. Determination of entrapment efficiency and production yield was done for trail batches. Characterization of formulation done by SEM,PXRD and FTIR. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
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Steroidal products have been found useful in inflammations associated with Covid 19. Prednisolone is one readily available steroid, which is often found as uncoated normal release tablets. Modified release prednisolone may be desirable in Covid 19 for sustained actions. This is expected to reduce dosing frequency and enhance compliance. This study is concerned with development of controlled release prednisolone using coating technology with bio-compatible, cross-linked starch-albumin films. Starches and proteins are excellent film formers with good flexibility, transparency, and bio-compatibility. The cross-linked starch-albumin films were prepared using glycerol as the plasticizer: starch (A), starch-albumin (B), starch-albumin cross-linked with formaldehyde at 1 % (C), 5 % (D) and 10 % (E). Equilibrium moisture sorption (EMS) at 100 % relative humidity, equilibrium swelling (ESC) in buffer solutions of pHs 2, 7 and 9, and DSC thermal properties were evaluated. In-vitro drug release from the film coated prednisolone tablets were evaluated in 0.1N HCl, water and phosphate buffer 8.0 as dissolution media. Films showed ESC in the order A>D>E>B>C;D>C>A>E>B and A>D>C>B>E in acidic, neutral and alkali media respectively. EMS was in the order B>E>A>D>C;with slight shift in the melting temperatures. In-vitro release at 240 min varied from 78 to 117 % (E>D>C>A>B);19 to 60 % (D>B>C>E>A) and 49 to 60 % (B>A>C>D>E) in 0.1N HCl, water and PBS respectively. Cross-linking improved the stability and swelling of films. The in-vitro release in alkaline medium suggests their usefulness for controlled drug delivery. New pH-responsive polymers, with improved physicochemical properties for coating prednisolone tablets were developed. Copyright © 2007, Nat. Inst. for Pharmaceutical Research and Development. All rights reserved.
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Background: Hypofibrinolysis, is the underlying reason behind hypercoagulability in severe COVID-19. Hypertension, cardiovascular diseases and diabetes are the prime comorbidities. Blood clotting, maintained by regulatory balance between procoagulants and anticoagulants, lead to equilibrium between coagulation and fibrinolysis. Fibrin clots made of meshwork of polymerized fibrin threads, generated by proteolysis of fibrinogen by thrombin, play a cardinal role in thrombosis. RBC, WBC and platelets get embroiled in the meshwork of fibrin thread to form clot . Clots made up thin, highly branched fibrin fibers with smaller pores are less susceptible to fibrinolysis, on the contrary clots with thick fibers, less branched with larger pores are prone to lysis. Factor VIIIa crosslinks to fibrin, also crosslinks alpha2-antiplasmin, TAFI, and PAI-2 to fibrin, to increase resistance to fibrinolysis and enhancing thrombosis risk. Aim(s): How COVID-19 comorbidities escalate hypofibrinolysis? Methods: Methods are from published literatures. Result(s): Fibrinogen levels are found to be enhanced in diabetes, with fibrin clots denser and resistant to fibrinolysis. Glycation of fibrinogen attributes to increased fibrin polymerization and crosslinkings, ensuing in abnormal clots. Altered fibrin structures, resistant to fibrinolysis are also observed in patients with coronary artery diseases and peripheral arterial diseases. Hypertension has also contributed to altered fibrin structures, with antihypertensive treatment increasing the clot susceptibility to lysis. Interestingly, platelet derived polyphosphate has been known to induce higher mass-length ratio of fibrin threads making it fibrinolysis resistant. More so, thromboembolic COVID-19 patients reported of elevated factor VIII, in comparison to patients without thromboembolisms. Severe COVID-19 patients also reported of elevated anticoagulant proteins as SERPINS, PAI-1, alpha2-antiplasmin and TAFI, reflective of impaired fibrinolysis. Supportively, expression of PAI-1 and TAFI are known to be enhanced in comorbidities. Conclusion(s): Altered fibrin structures coupled with enhanced anticoagulant production, can lead to hypofibrinolysis, which predisposes to thromboembolisms in some severe COVID-19 patients with comorbidities.
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The majority of processes that occur in daily cell life are modulated by hundreds to thousands of dynamic protein-protein interactions (PPI). The resulting protein complexes constitute a tangled network that, with its continuous remodeling, builds up highly organized functional units. Thus, defining the dynamic interactome of one or more proteins allows determining the full range of biological activities these proteins are capable of. This conceptual approach is poised to gain further traction and significance in the current postgenomic era wherein the treatment of severe diseases needs to be tackled at both genomic and PPI levels. This also holds true for COVID-19, a multisystemic disease affecting biological networks across the biological hierarchy from genome to proteome to metabolome. In this overarching context and the current historical moment of the COVID-19 pandemic where systems biology increasingly comes to the fore, cross-linking mass spectrometry (XL-MS) has become highly relevant, emerging as a powerful tool for PPI discovery and characterization. This expert review highlights the advanced XL-MS approaches that provide in vivo insights into the three-dimensional protein complexes, overcoming the static nature of common interactomics data and embracing the dynamics of the cell proteome landscape. Many XL-MS applications based on the use of diverse cross-linkers, MS detection methods, and predictive bioinformatic tools for single proteins or proteome-wide interactions were shown. We conclude with a future outlook on XL-MS applications in the field of structural proteomics and ways to sustain the remarkable flexibility of XL-MS for dynamic interactomics and structural studies in systems biology and planetary health.
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Background and Aim: World-wide, Kawasaki disease (KD) is known to affect predominantly children under the age of 5, mostly boys. An increasing incidence has been reported from select countries, as well as seasonal differences, although with great variation among reports. Sweden has unique population-based health registers which can be linked to population registers via a personal number. In this study we therefore utilized population-based data over a period of more than 30 years to investigate demographics and epi-demiology of Kawasaki disease in a Scandinavian country. Method(s): Individuals receiving a diagnosis of Kawasaki disease in Sweden from 1987-2018 (before the occurrence of MIS-C) were identified by ICD9 and ICD10 discharge diagnoses in the Patient register at the National Board of Health and Welfare, and basic demographic information obtained by cross-linking with popula-tion registers at Statistics Sweden. Age-stratified population statis-tics were also retrieved during the corresponding time-period. Result(s): A total of 1,785 individuals with a KD diagnosis during the study period were identified, confirming a relatively low incidence in the Scandinavian population. Less than 5% of the cases were born in another country. The majority of cases (78%) occurred before 5 years of age, and there was a male dominance (61%). Sweden has a temperate climate of the northern hemisphere, and analysis of case distribution over the yearly cycle revealed peak incidence during the winter months. Notably, the incidence rose from around 6/100,000 lt;5-year-olds to 15/100,000 lt;5-year-olds during the 30-year study period. Two years with prominently higher incidence than prior and following years were observed. A large part of the rise in incidence seems to be associated with immigration and occurred before the occurrence of Multisystem Inflammatory Syndrome in Children related to SARS-CoV-2. Conclusion(s): Demographic parameters for Kawasaki disease in Sweden regarding age and sex distribution are similar to previous reports from other countries. Our data from a 30-year study period of population-based observations confirm peak incidence during the cold period, and a rising incidence during recent years, even before the occurrence of MIS-C. Our data also indicate outbursts during two years and immigration-associated patterns in rise in incidence.
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Purpose : The effect of coronavirus disease 2019 (COVID-19) on ophthalmic surgical case numbers in Australia and globally remains poorly characterised. Increased incidence of COVID-19 in Australia between March and April 2020 led to a national lockdown and elective surgery restrictions. The aim of this population-based study was to quantify the early impact of COVID-19 on ophthalmic surgery in Australia, comparing surgical service rates in 2019 and 2020. Methods : Retrospective analysis of the number of ophthalmic surgical services in 2019 and 2020 in all Australian States and Territories, as recorded by Medicare (Australian Government-funded universal health insurance scheme subsidising healthcare costs for Australian residents). Monthly surgical service rates were calculated and Poisson regression was used to compare the change in service rates between months. Results : Between March and April 2020, surgical service rates decreased for: cataract surgery (by 71%, 95% CI: 70-72%), cataract surgery with minimally invasive glaucoma surgical device insertion (by 71%, 95% CI: 65-75%), pterygium removal (by 67%, 95% CI: 60- 72%), corneal transplantation (by 31%, 95% CI: 9-48%), and collagen crosslinking for corneal ectasias (by 35%, 95% CI: 18-48%). Comparatively, service rates for these surgeries did not differ or decreased less between March and April 2019. Interestingly, glaucoma filtration surgery rates decreased between March and April in 2020 (by 44%, 95% CI: 29- 56%) and also in 2019 (by 45%, 95% CI: 31-55%), whilst retinal detachment surgery rates were unchanged between these months in 2020 (crude decrease 9%, 95% CI: -28 to 16%) and 2019 (crude decrease 11%, 95% CI: -26 to 9%). Conclusions : Despite relatively low rates of COVID-19 community transmission in Australia in 2020, ophthalmic surgical service rates decreased during months in lockdown and with restrictions, largely for non-time-critical conditions. These data may have health planning implications as the pandemic continues, with future lockdowns and restrictions possible, especially as COVID-19 variants emerge.
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Background: SARS-CoV-2 pandemic brought new attention to blood substitutes as a potential remedy for treatment of COVID-19 associated hypoxemia and more importantly to provide relief for sagging blood banks. In fact the American Red Cross declared a national blood crisis, the worst in decades. Although commercialization attempts of 1st generation blood substitutes have been unsuccessful due to toxicity and/or poor efficacy problems, the artificial oxygen carriers' field is rapidly expanding again creating more innovative products. To attenuate the adverse effects of blood substitutes caused by intrinsic toxicity of Hb we implemented a novel concept of 'pharmacologic cross-linking' and formulated a safe and effective blood substitute - HemoTech. Methods: HemoTech consists of pure bovine Hb cross-linked intramolecularly with o-ATP and intermolecularly with oadenosine and conjugated with reduced glutathione (GSH). HemoTech cGMP manufacturing includes a novel, validated orthogonal technology platform for effective clearance of endotoxin, prions and non-enveloped and enveloped viruses. Regulatory mandated requirements have been met including CMC and GLP non-clinical pharmacology, toxicology, genotoxicity and efficacy studies. HemoTech's clinical 'proof-of-concept' was performed in children with sickle cell anemia. Results: HemoTech is formulated as a 6.5 g/dL modified Hb solution in oxy- or carbon monoxy-form, enriched with electrolytes and mannitol. The 'pharmacologic cross-linking' does not interfere with Hb respiratory function, but eradicates Hb's intrinsic toxicity and provides Hb molecules with new medicinal properties of ATP, adenosine and GSH. The results of preclinical and clinical studies indicate that HemoTech is non-toxic and works as a physiological oxygen carrier with prolonged intravascular persistence, is vasodilatory and can reduce vasoconstriction that follows hemorrhage, has antioxidant and anti-inflammatory activities, and erythropoietic properties. Conclusion: HemoTech promises to be an effective blood substitute for various clinical indications.
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Heparin is a kind of glycosaminoglycan drug with a complex structure, which is a mixture of polysaccharides with different chain lengths composed of hexuronic acid, aminohexose and its derivatives.Hexuronic acids are L-aduronic acid and D-glucuronic acid, aminohexose is α -D-glucosamine, and the modification of derivatives includes sulfation and acetylation.As a natural biomacromolecule, heparin has a variety of biological activities.It has been discovered for more than a hundred years and has good anticoagulant effect, which is clinically the first choice for anticoagulant and prevention and treatment of thromboembolic diseases.It has been discovered that there are more than one hundred functional proteins that interact with heparin.Heparin can bind to a variety of proteins and exert a variety of biological activities such as anticoagulant, anti-inflammatory, antiviral, and anti-tumor. The anticoagulant mechanism of heparin has been explained in detail, but its anti-inflammatory, antiviral, anti-tumor and other non-anticoagulant biolo-gical activities are still under extensive research, and these activities also have the potential to be developed into new drugs and new materials.Derivatives which with low anticoagulant activity and high antiangiogenic activity have been developed.In addition, sepsis-induced coagulopathy was common in patients with severe pneumonia caused by COVID-19 during the global outbreak of novel coronavirus epidemic.Heparin is effective in improving coagulation disorders and is likely to provide a better prognosis in patients with severe pneumonia.Due to its better biological activity, it also has potential applications in the field of new materials, such as being a cross-linking agent in the formation of hydrogels, and as a surface modifier of nanoparticles. This article consists of five parts, through which the author will first review the pharmacological activities of heparin in anticoagulation, anti-inflammatory and anti-tumor activities, then introduce the application of heparin in the new coronavirus, and finally give an overview of the application of heparin in new materials.
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The possibility of using commercial bayberry tannin (BT) from a Chinese source as a cross-linker and functional additive to develop soybean protein isolate (SPI)-based films was explored in this study by using the solvent casting method. In particular, the impacts of BT loading on the tensile strength, microstructure, thermal stability, water resistance and antioxidant capacity were fully investigated. The results reveal that SPI incorporated with BT yielded a phenolic-protein hybrid whose relevant films exhibited an improvement in tensile strength of around two times greater compared with native SPI as a result of the formed interactions and covalent cross-links, which could be proven using FTIR spectroscopy. The introduction of BT also led to the compact microstructure of SPI-BT films and enhanced the thermal stability, while the water vapor permeability was reduced compared with the control SPI film, especially at high loading content of tannin. Additionally, the use of BT significantly promoted the antioxidant capacity of the SPI-based films according to DPPH radical scavenging assay results. On this basis, Chinese bayberry tannin is considered a promising natural cross-linker and multifunctional additive that can be dedicated to developing protein-derived films with antioxidant activity for food packaging applications.
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For decades, scientific efforts were focused on the improvement of the effectiveness of the therapeutic antibodies, mainly in order reduce the dosage and thus lower the side-effects and costs. P4A1, a potent SARS-CoV-2 virus neutralizing antibody was already engineered to contain Fc fragment mutations, that dramatically increased the blood circulation time. In this work, we aimed to further enhance this neutralizing antibody efficacy by creating a next-generation virus neutralizing agent based on the P4A1 and conjugated with a highly processive Bacillus amyloliquefaciens RNase (barnase). Barnase itself is known to act as a mild toxin that drives the cells to apoptosis, and we propose that its RNase activity may enhance the protective effect through the hydrolysis of viral RNA in infected cells, and thereby additionally preventing pathogen replication. The main challenge in the assembly of such molecule is the intrinsic barnase toxicity in mammalian cells, what precludes the possibility to express it as a fusion protein. Further, we had shown that barnase, being a small (12.5 kDa) protein, contains very few surface reactive moieties that are available for conventional chemical crosslinking strategies. Therefore, the antibody-barnase fusion protein was obtained by enzymatic conjugation via the sortase A enzyme. The reaction conditions for bacterially expressed barnase and HEK293 derived P4A1 modified to contain heavy chain C-terminal sortase motif were thoroughly optimized and the reaction yield approached 80%. The immunotoxin RBD binding EC50 was not found to differ from the unconjugated P4A1 antibody and barnase activity was found to be 33% of the one for unmodified enzyme. Thus, we obtained the promising immunotoxin with a good yield, which had retained its RNase activity for the further in vitro virus neutralization studies.
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Numerous disposable surgical masks (DSMs) were consumed with the development of COVID-19 epidemic. Non-solid products recovered by pyrolysis is more than twenty species with low added value. Therefore, the search for a reasonable carbonization method can not only alleviate the pressure of global plastic pollution, but also produce considerable economic value. Here it is found that microwave cross-linking can promote the substitution of hydrogen atom in the polymer master chain of DSMs by hydrogen atom, which can reorganize the easily cracked DSMs into sp2-hybridized aromatic carbon, it can maintain 51.2% carbon yield at 1000℃. The difference between the DSMs-based porous carbon obtained by in-situ and post-processing N doping was further compared, and it was found that the specific surface area of the activated in-situ doped sample (P-SNO@DSMs) was as high as 2278 m2·g-1, which had rich hierarchical pore structure and high heteroatoms doping rate. Benefiting from the synergistic effect of heteroatoms and hierarchical holes, P-SNO@DSMs sulfur cathode delivers a high specific capacity of 1550 mAh·g-1 at 0.1C and exhibits excellent long-term cycling performance with the smaller capacity decay of 0.13% per cycle after 400 cycles. In this work, clean and efficient microwave cross-linking not only realized the efficient recovery of waste DSMs, but also the application of the prepared materials can be broadened by adding additional heteroatomic sources in the process of microwave cross-linking.