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2022 ◽  
Vol 90 (1) ◽  
pp. 5
Author(s):  
Franck Marquet ◽  
Valentina D’Atri ◽  
Davy Guillarme ◽  
Gerrit Borchard

The objective of this study was to qualitatively evaluate a Fab-targeting ligand preparation containing free thiol groups in the hinge region by using bevacizumab as a model. The evaluation focused on the purification of fragments through a nonaffinity-based process using a centrifugal ultrafiltration technique and mild reduction conditions for the intact production of F(ab’) fragments with specific inter-heavy-chain disulfide bonds cleavage. Under these conditions, F(ab’) fragments with a defined chemical composition were successfully obtained via proteolytic digestion followed by a controlled reduction reaction process maintaining the integrity of the binding sites. The ultrafiltration purification technique appears to be suitable for the removal of the digestive enzyme but inefficient for the removal of Fc fragments, thus requiring additional processing. A suitable analytical strategy was developed, allowing us to demonstrate the reformation of disulfide bridges between the two reduced cysteines within F(ab’) fragments.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Paolo Marco Pietro Spissu ◽  
Simone Angius ◽  
Maria Francesca Marchetti ◽  
Ludovica Caggiari ◽  
Alessandra Gioi ◽  
...  

Abstract Aims Transient constrictive pericarditis (TCP) is a rare manifestation which can occur in up to 15% of cases of acute pericarditis and most have resolution after 3 months of anti-inflammatory therapy. Methods and results We present the case of a young guy who showed up at our emergency department complaining of pericarditic chest pain and fever up to 39 °C degrees since the previous 4 days. After physical examination, electrocardiogram, blood tests, chest X-ray, and echocardiography acute pericarditis with severe pericardial effusion (more than 20 mm of thickness) were diagnosed and an empiric anti-inflammatory therapy with ibuprofen and colchicine was started. After 2 weeks of therapy, patient was not clinically improving with a worsened pericardial effusion and only a mild reduction of inflammatory markers. During an echocardiographic examination, features of constrictive physiology were discovered: respirophasic interventricular septal shift, increased respiratory variation of the mitral and tricuspidal inflow, plethoric inferior vena cava, and ‘annulus reversus’ and ‘annulus paradoxus’ on Tissue Doppler Imaging (TDI). Cardiac magnetic resonance (CMR) was also performed to confirm the diagnosis of acute pericardial constriction: it revealed increased T2-weighted imaging signal and increased Delayed Gadolinium Enhanced (DGE) signal, respectively consistent with oedema and with neovascularization, both suggestive of acute pericardial inflammation. Therefore, oral low doses corticosteroid was started After 2 weeks course of ‘triple therapy’ the patient was clinically improved and the echocardiographic features of constrictive physiology were no longer present thus allowing his discharge and the continuation of therapy at home. Conclusions This case was remarkable because it showed that constrictive pericarditis may present in a reversible form with medical therapy, this meaning it is due to pericardial oedema, inflammation and fibrin deposition similar to acute pericarditis rather than the pericardial fibrosis and calcification more commonly seen in chronic pericardial constriction.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiafeng Yu ◽  
Xingtao Sun ◽  
Xin Tong ◽  
Jixin Zhang ◽  
Jie Li ◽  
...  

AbstractThe rational design of high-temperature endurable Cu-based catalysts is a long-sought goal since they are suffering from significant sintering. Establishing a barrier on the metal surface by the classical strong metal-support interaction (SMSI) is supposed to be an efficient way for immobilizing nanoparticles. However, Cu particles were regarded as impossible to form classical SMSI before irreversible sintering. Herein, we fabricate the SMSI between sputtering reconstructed Cu and flame-made LaTiO2 support at a mild reduction temperature, exhibiting an ultra-stable performance for more than 500 h at 600 °C. The sintering of Cu nanoparticles is effectively suppressed even at as high as 800 °C. The critical factors to success are reconstructing the electronic structure of Cu atoms in parallel with enhancing the support reducibility, which makes them adjustable by sputtering power or decorated supports. This strategy will extremely broaden the applications of Cu-based catalysts at more severe conditions and shed light on establishing SMSI on other metals.


Biology Open ◽  
2021 ◽  
Author(s):  
Yixing Wu ◽  
Ying Bai ◽  
David G. McEwan ◽  
Liz Bentley ◽  
Dimitra Aravani ◽  
...  

The small GTPase ARF family member ARL15 gene locus is associated in population studies with increased risk of type 2 diabetes, lower adiponectin and higher fasting insulin levels. Previously, loss of ARL15 was shown to reduce insulin secretion in a human β-cell line and loss of function mutations are found in some lipodystrophy patients. We set out to understand the role of ARL15 in adipogenesis and showed that endogenous ARL15 palmitoylated and localised in the Golgi of mouse liver. Adipocyte overexpression of palmitoylation-deficient ARL15 resulted in redistribution to the cytoplasm and a mild reduction in expression of some adipogenesis-related genes. Further investigation of the localisation of ARL15 during differentiation of a human white adipocyte cell line showed that ARL15 was predominantly co-localised with a marker of the cis face of Golgi at the preadipocyte stage and then translocated to other Golgi compartments after differentiation was induced. Finally, co-immunoprecipitation and mass spectrometry identified potential interacting partners of ARL15, including the ER-localised protein ARL6IP5. Together, these results suggest a palmitoylation dependent trafficking-related role of ARL15 as a regulator of adipocyte differentiation via ARL6IP5 interaction.


Author(s):  
Amit Nahum ◽  
Keren Rochwerger-Biham

Introduction: The epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19, continuous to affect most of the world's population. In children, the respiratory and systemic involvement appears to have a much more benign course in comparison to adults, with almost no fatalities reported. However, we are encountering a post-infectious immune mediated condition, termed, multisystem inflammatory syndrome in children (MIS-C). In most cases the main features are prolonged fever and elevation of inflammatory markers, many of the patients present with abdominal pain and varying degree of myocardial involvement from mild reduction in cardiac output to the most alarming manifestation of cardiovascular shock. Results: We present two patients with unusual manifestations of MIS-C, related to post COVID-19 infection, an infant born to a mother who was severely ill at the very end of pregnancy, presenting with prolonged fever, rash, pericardial effusion, and evidence of coronary arteries wall thickening as a result of inflammation, and, a teenage girl with severe cardiac tamponade without the more common cardiac manifestations of myocardial involvement. Discussion: Post COVID-19 MIS-C can present in a wide variety of manifestations. The pathophysiologic mechanism underlying these inflammatory responses in infants are yet to be elucidated. Physicians should be aware of such presentations since rapid diagnosis and treatment are key for favorable outcome.


2021 ◽  
pp. 62-64
Author(s):  
I. Vanessa Marin Collazo

A 58-year-old, right-handed man with a medical history of nephrolithiasis, essential hypertension, and type 2 diabetes sought care for a 6-year history of gait impairment. Initially, he noted subtle left foot and ankle weakness with associated falls that progressed over time. Two to 3 years later he again noted progressive left leg weakness and new arm weakness. Subsequently, progressive pain developed on the soles of his feet in addition to edema with erythematous discoloration around the left ankle and foot. On neurologic examination, he was found to have mild upper motor neuron pattern weakness in the left arm and leg, most pronounced in the left hand finger extensor and left hip flexion and abduction. Left patellar reflex was brisk, and there was an extensor Babinski sign on the left. There was mild reduction in pinprick sensation in both feet. His gait was spastic with left leg circumduction. Magnetic resonance imaging of the brain showed left-sided predominant periventricular and subcortical T2 fluid-attenuated inversion recovery hyperintensities. Magnetic resonance imaging of the cervical and thoracic spinal cord showed intramedullary cord T2 signal hyperintensities, eccentrically located on the left at C3, C5, C6, on the right at C7 to T1, and centrally at T4/T5 and T8/T9. A diagnosis of primary progressive multiple sclerosis was made. The patient met the 2017 McDonald criteria for primary progressive multiple sclerosis. After the diagnosis was confirmed and comprehensive education about the disease and the role of disease-modifying therapy was discussed with the patient, he was started on ocrelizumab. Gabapentin was started for management of painful foot paresthesias. Vitamin D3 supplementation was started. Physical therapy was also initiated. Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system and is the leading cause of disability in the young population. Approximately 1 million people in the United States currently have multiple sclerosis.


Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1328
Author(s):  
Ahmed H. Abed ◽  
Esraa F. Hegazy ◽  
Sherif A. Omar ◽  
Rehab M. Abd El-Baky ◽  
Ahmed A. El-Beih ◽  
...  

Staphylococcus species cause diseases in animals and humans. The prevalence and antimicrobial profiles of Staphylococcus spp. in animals and human samples in the Minya Governorate, Egypt, were determined, and resistance- and virulence-associated genes were observed in multidrug-resistant (MDR) isolates. Moreover, the antibacterial effect of carvacrol essential oil (EO) on the MDR isolates was studied. A total of 216 samples were aseptically collected from subclinically mastitic cow’s milk (n = 100), sheep abscesses (n = 25) and humans (n = 91). Out of 216 samples, a total of 154 single Staphylococcus species (71.3%) were isolated. The most frequent bacterial isolates were S. aureus (43%), followed by S. schleiferi (25%), S. intermedius (12%), S. xylosus (12%), S. haemolyticus (4.5%), S. epidermidis (2%) and S. aurecularis (1%). Haemolytic activity and biofilm production were detected in 77 and 47% of isolates, respectively. Antimicrobial susceptibility testing showed a high degree of resistance to the most commonly used antimicrobials in human and veterinary practices. The mecA, vanA, vanC1 and ermC resistance genes were detected in 93, 42, 83 and 13% of isolates, respectively. Moreover, hla, icaA and icaD virulence genes were detected in 50, 75 and 78% of isolates, respectively. Carvacrol effectively inhibited the growth of all tested isolates at concentrations of 0.1, 0.05 and 0.04% while a concentration of 0.03% inhibited 75% of isolates. Interestingly, some phenotypic changes were observed upon treatment with a carvacrol oil concentration of 0.03%. All the treated MDR Staphylococcus isolates changed from multidrug resistant to either susceptible or intermediately susceptible to 2–3 antimicrobials more than parental bacterial isolates. Real-time PCR was applied for the detection of the differential expression of mecA and vanC1 genes before and after treatment with carvacrol which revealed a mild reduction in both genes’ expression after treatment. Staphylococcus spp. Containing MDR genes are more likely to spread between humans and animals. From these results, carvacrol EO is a promising natural alternative to conventional antimicrobials for pathogens impacting human health and agriculture due to its potential antimicrobial effect on MDR pathogens; even in sub-lethal doses, carvacrol EO can affect their phenotypic properties and genes’ expression.


2021 ◽  
Vol 22 (19) ◽  
pp. 10879
Author(s):  
Agnieszka Wojtkielewicz ◽  
Urszula Kiełczewska ◽  
Aneta Baj ◽  
Jacek W. Morzycki

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO4 oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.


2021 ◽  
Vol 7 (10) ◽  
pp. 804
Author(s):  
Chad J. Johnson ◽  
Emily F. Eix ◽  
Brandon C. Lam ◽  
Kayla M. Wartman ◽  
Jennifer J. Meudt ◽  
...  

Candida auris readily colonizes skin and efficiently spreads among patients in healthcare settings worldwide. Given the capacity of this drug-resistant fungal pathogen to cause invasive disease with high mortality, hospitals frequently employ chlorhexidine bathing to reduce skin colonization. Using an ex vivo skin model, we show only a mild reduction in C. auris following chlorhexidine application. This finding helps explain why chlorhexidine bathing may have failures clinically, despite potent in vitro activity. We further show that isopropanol augments the activity of chlorhexidine against C. auris on skin. Additionally, we find both tea tree (Melaleuca alternifolia) oil and lemongrass (Cymbopogon flexuosus) oil to further enhance the activity of chlorhexidine/isopropanol for decolonization. We link this antifungal activity to individual oil components and show how some of these components act synergistically with chlorhexidine/isopropanol. Together, the studies provide strategies to improve C. auris skin decolonization through the incorporation of commonly used topical compounds.


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