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The COVID-19 pandemic has been fueled by novel variants of concern (VOC) that have increased transmissibility, receptor binding affinity, and other properties that enhance disease. The goal of this study is to characterize unique pathogenesis of the Delta VOC strain in the K18-hACE2-mouse challenge model. Challenge studies suggested that the lethal dose of Delta was higher than Alpha or Beta strains. To characterize the differences in the Delta strain’s pathogenesis, a time-course experiment was performed to evaluate the overall host response to Alpha or Delta variant challenge. qRT-PCR analysis of Alpha- or Delta- challenged mice revealed no significant difference between viral RNA burden in the lung, nasal wash or brain. However, histopathological analysis revealed high lung tissue inflammation and cell infiltration following Delta- but not Alpha-challenge at day 6. Additionally, pro-inflammatory cytokines were highest at day 6 in Delta-challenged mice suggesting enhanced pneumonia. Total RNA-sequencing analysis of lungs comparing infected to uninfected mice revealed that Alpha-challenged mice have more total genes differentially activated, conversely, Delta-challenged mice have a higher magnitude of differential gene expression. Delta-challenged mice have increased interferon-dependent gene expression and IFN-γ production compared to Alpha. Analysis of TCR clonotypes suggested that Delta challenged mice have increased T-cell infiltration compared to Alpha challenged. Our data suggest that Delta has evolved to engage interferon responses in a manner that may enhance pathogenesis. Thein vivoandin silicoobservations of this study underscore the need to conduct experiments with VOC strains to best model COVID-19 when evaluating therapeutics and vaccines.ImportanceThe Delta variant of SARS-CoV-2 is known to be more transmissible and cause severe disease in human hosts due to mutations in its genome that are divergent from previous variants of concern (VOC). Our study evaluates the pathogenesis of Delta in the K18-hACE2 mouse model compared to the Alpha VOC. We observed that relative to Alpha, Delta challenge results in enhanced inflammation and tissue damage with stronger antiviral responses. These observations provide insight into Delta’s unique pathogenesis.

The triggers for the development of multiple sclerosis (MS) have not been fully understood to date. One hypothesis proposes a viral etiology. Interestingly, viral proteins from human endogenous retroviruses (HERVs) may play a role in the pathogenesis of MS. Allelic variants of the HERV-K18 env gene represent a genetic risk factor for MS, and the envelope protein is considered to be an Epstein–Barr virus-trans-activated superantigen. To further specify a possible role for HERV-K18 in MS, the present study examined the immunogenicity of the purified surface unit (SU). HERV-K18(SU) induced envelope-specific plasma IgG in immunized mice and triggered proliferation of T cells isolated from these mice. It did not trigger phenotypic changes in a mouse model of experimental autoimmune encephalomyelitis. Further studies are needed to investigate the underlying mechanisms of HERV-K18 interaction with immune system regulators in more detail.

Purpose. To explore and analyze the therapeutic effect of gamma globulins (GG) on Kawasaki disease (KD) in children and the influencing factors of short-term prognosis. Methods. First, 90 pediatric KD patients admitted between January 2019 and January 2021 were selected and divided into a control group ( n = 40 ) and a research group ( n = 50 ) according to the difference in treatment. In addition to routine treatment and nursing given to both groups, control group was given aspirin (ASA), based on which research group was supplemented with GG therapy. The treatment outcome and adverse events (AEs) of the two cohorts of patients were analyzed and compared, and the influencing factors of children’s short-term prognosis were analyzed by logistics multivariate analysis. Results. Research group had a statistical higher overall response rate than control group, with significantly fewer cases suffering from AEs such as nausea and vomiting, diarrhea, rash, dizziness and headache, and coronary artery injury. On the other hand, logistics multivariate analysis identified that gender, body mass index (BMI), onset time, platelet (PLT), and treatment mode all independently influence the short-term prognosis of children with KD. Conclusions. GG therapy is effective in treating pediatric KD patients and can effectively prevent AEs. In addition, gender, BMI, onset-to-treatment time, PLT, C-reactive protein (CRP), and treatment methods are independent risk factors for short-term prognosis of children with KD.

Compared to the original ancestral strain of SARS-CoV-2, the Delta variant of concern has shown increased transmissibility and resistance toward COVID-19 vaccines and therapies. However, the pathogenesis of the disease associated with Delta is still not clear. In this study, using K18-hACE2 transgenic mice, we assessed the pathogenicity of the Delta variant by characterizing the immune response following infection. We found that Delta induced the same clinical disease manifestations as the ancestral SARS-CoV-2, but with significant dissemination to multiple tissues, such as brain, intestine, and kidney. Histopathological analysis showed that tissue pathology and cell infiltration in the lungs of Delta-infected mice were the same as in mice infected with the ancestral SARS-CoV-2. Delta infection caused perivascular inflammation in the brain and intestinal wall thinning in K18-hACE2 transgenic mice. Increased cell infiltration in the kidney was observed in both ancestral strain- and Delta-infected mice, with no clear visible tissue damage identified in either group. Interestingly, compared with mice infected with the ancestral strain, the numbers of CD45+ cells, T cells, B cells, inflammatory monocytes, and dendritic cells were all significantly lower in the lungs of the Delta-infected mice, although there was no significant difference in the levels of proinflammatory cytokines between the two groups. Our results showed distinct immune response patterns in the lungs of K18-hACE2 mice infected with either the ancestral SARS-CoV-2 or Delta variant of concern, which may help to guide therapeutic interventions for emerging SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 variants, with the threat of increased transmissibility, infectivity, and immune escape, continue to emerge as the COVID-19 pandemic progresses. Detailing the pathogenesis of disease caused by SARS-CoV-2 variants, such as Delta, is essential to better understand the clinical threat caused by emerging variants and associated disease. This study, using the K18-hACE2 mouse model of severe COVID-19, provides essential observation and analysis on the pathogenicity and immune response of Delta infection. These observations shed light on the changing disease profile associated with emerging SARS-CoV-2 variants and have potential to guide COVID-19 treatment strategies.

Objective. To investigate the efficacy of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia and its effect on Th1/Th2 cytokine levels. Method. From January 2021 to January 2022, 100 children diagnosed with refractory mycoplasma pneumonia were randomly divided into 2 groups (50 cases in each one), the control group was treated with azithromycin plus comprehensive basic treatment, and the treatment group was treated with combined treatment on the basis of the control group, gamma globulin therapy; the treatment effect and cytokine levels of the two groups were compared. Results. Th1, Th2, and Th1/Th2 before treatment were not significantly different between the two groups. Th1, Th2, and Th1/Th2 in the treatment group were significantly downregulated compared with those in the control group after treatment. The levels of IgG, IgA, and IgM in the treatment group were not significantly different from those in the control group before treatment but were significantly upregulated after treatment. IL-10, IL-6, and IL-2 levels were also significantly increased in the treatment group. The disappearance time of clinical symptoms such as fever, cough, and pulmonary rales in the treatment group was significantly shorter than that in the control group, and the cure rate in the treatment group was significantly better than that in the control group. Conclusion. The clinical effect of gamma globulin combined with azithromycin sequential therapy in the treatment of children with refractory mycoplasma pneumonia is remarkable, which can reduce inflammatory factors, improve patients’ immunity, and promote disease recovery.

This study aimed to investigate changes in the serum protein profiles of healthy newborn Korean calves and provide a reference index for these changes during growth. The serum protein composition of 15 healthy bovine calves aged 1 week to 4 months was analyzed using electrophoresis. The albumin to globulin (A/G) ratio increased until calves reached 2 months (1.3 ± 0.2) and then decreased until they reached 4 months (1.1 ± 0.1). Albumin concentrations increased up to month 2 (3.4 ± 0.1) and decreased until month 4 (3.2 ± 0.2). α-1 globulin concentrations decreased up to week 4 (0.4 ± 0.1) and then increased until month 2 (0.6 ± 0.1). γ globulin decreased until month 2 (0.7 ± 0.2) and then increased until month 4 (1.1 ± 0.3). These age-related changes in protein concentrations indicate the importance of considering age in calf blood tests. The γ globulin concentration was at its highest in the first week, due to colostrum intake, and decreased to reach its lowest at 2 months, when passive maternal immunity is also at its lowest. Therefore, provision of sufficient passive immunity through the colostrum in neonatal calves might enable healthy growth.Cette étude visait à examiner les changements dans les profils de protéines sériques de veaux coréens nouveau-nés et de fournir un index de référence pour ces changements durant la croissance. La composition des protéines sériques de 15 veaux en santé âgés de 1 semaine à 4 mois a été analysée par électrophorèse. Le ratio albumine:globuline (A/G) a augmenté jusqu’à ce que les veaux atteignent l’âge de 2 mois (1,3 ± 0,2) et diminuait par la suite jusqu’à ce qu’ils aient 4 mois (1,1 ± 0,1). Les concentrations d’albumine augmentèrent jusqu’au mois 2 (3,4 ± 0,1) et diminuèrent ensuite jusqu’au mois 4 (3,2 ± 0,2). Les concentrations de α-1 globuline ont diminué jusqu’à la semaine 4 (0,4 ± 0,1) et ont par la suite augmenté jusqu’au mois 2 (0,6 ± 0,1). Les concentrations de γ globuline ont diminué jusqu’au mois 2 (0,7 ± 0,2) et ont par la suite augmenté jusqu’au mois 4 (1,1 ± 0,3). Ces changements dans les concentrations de protéines en fonction de l’âge démontrent l’importance de considérer l’âge lors des tests sanguins chez les veaux. La concentration de γ globuline était à son maximum durant la première semaine, due à l’ingestion de colostrum, et diminua par la suite pour atteindre un minimum à 2 mois, alors que l’immunité maternelle passive est à son plus bas. Ainsi, le fait de fournir suffisamment d’immunité passive

A cannabidiol (CBD) oral solution (Epidiolex®) has been approved by the United States Food and Drug Administration to treat seizure conditions. However, the biomedical and pharmaceutical applications of CBD are hindered partially due to a limited understanding of CBD's pharmacokinetic behaviors, such as its interactions with plasma proteins. Herein, we investigated the molecular interactions between CBD and two plasma proteins, namely, human serum albumin (HSA) and γ-globulin, using biophysical techniques including surface plasmon resonance (SPR), isothermal titration calorimetry, and differential scanning calorimetry, as well as molecular docking. CBD bound to HSA and γ-globulin in an exothermic manner (enthalpy: -9.3 ×10

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disease in which peripheral sensory and motor nerves of the four limbs are impaired due to autoimmune mechanism-induced demyelinating changes through a 2-month or longer chronic course. The incidence of complication by cranial neuropathy has been reported to be 15%, but there have been very few reports on disorder of the vagus nerve and its branch, the recurrent nerve. We report a patient who developed left recurrent nerve palsy with CIDP. The patient was a 48-year-old male. The disease developed as progressive muscle weakness and numbness of the four limbs 3 years before and was diagnosed as CIDP. The symptoms had been improved by high-dose intravenous gamma-globulin therapy. However, from 2 months before he became aware of breathy hoarseness, and bilateral decreased grip strength and sensory disturbance of the upper and lower limbs recurred and progressed. On laryngoscopy disorder of left vocal fold movement and glottal closure incompetence during phonation were observed, and neurogenic changes were detected in the left thyroarytenoid muscle by needle electromyography for the intrinsic laryngeal muscles. High-dose intravenous gamma-globulin therapy was performed and left vocal fold movement recovered with recovery of bilateral grip strength and sensory disturbance of the upper and lower limbs, and phonation was also normalized.

Red tide events, caused by a toxin producing dinoflagellate, Karenia brevis, occur annually in Florida and Texas. These events lead to health risks for both humans and wildlife that utilize coastal environments. Brevetoxins, potent lipophilic neurotoxins produced by K. brevis, modulate immune responses in laboratory studies with model organisms and in the natural environment in both humans and wildlife. Studies show that brevetoxins activate immune cells, stimulate production of gamma-globulins, cytokines, and neutrophils, modulate lysozyme activity, induce apoptosis, and modulate lymphocyte proliferation in marine species. The objective of this review was to summarize brevetoxin-induced immunotoxicity in marine animals based on available peer-reviewed literature about K. brevis blooms and associated health concerns and propose putative toxicity pathways. This review identifies knowledge gaps within current brevetoxin induced immunotoxicity research, including assessing the long-term impacts of brevetoxin exposure, elucidating the mechanistic linkages between brevetoxins and immune cells, and evaluating repeated and chronic versus acute brevetoxin exposure implications on overall organismal health. The putative immunotoxicity pathways based on evidence from brevetoxin-exposure in marine fauna described in this review represent a useful tool and resource for researchers, wildlife managers, and policy makers. This review and proposed putative immunotoxicity pathways will inform decisions regarding the risks of algal blooms, as it pertains to marine animal health.

Interactions between layered double hydroxide (LDH) nanomaterials and plasma proteins according to their particle size and surface charge were evaluated. The LDHs with different particle size (150, 350 and 2000 nm) were prepared by adjusting hydrothermal treatment and urea hydrolysis and subsequent organic coating with citrate, malite and serite was applied to control the surface charge (ζ-potential: −15, 6 and 36 mV). Adsorption isotherms and Stern–Volmer plots for fluorescence quenching indicated that the human blood plasma had weak interactions toward all the types of LDHs. The adsorption isotherms did not show significant differences in the size and surface charges, while the fluorescence quenching ratio increased with the increase in the surface charge, implying that electrostatic interaction played a major role in their interactions. The fluorescence quenching of three types of plasma proteins (human serum albumin, γ-globulin and fibrinogen) by the surface charge-controlled LDHs suggested that the proteins adsorbed on the LDHs with a single layer and additional proteins were weakly adsorbed to surround the LDHs with adsorbed proteins. It was concluded that the LDH nanomaterials are fairly compatible for blood components due to the protein corona while the electrostatic interaction can affect their interaction with the proteins.

International audience; Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT.Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically.Results: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level

Background: the torpid progress of chronic eye disorders, with conventional treatments, impels the alternative use of immunomodulators.Objective: to describe the use of immunomodulators in patients with chronic eye disorders that do not improve with conventional treatments, attended to at the department of immunoallergy of the Clinic of Medical Specialties of Granma, from 2017 through 2020.Methods: a descriptive study was carried out at the aforementioned clinic and during the period herein declared. Out of a universe of 101 patients, older than 18 years, 96 were chosen by intentional sampling who consented to be treated with immunomodulators, from January 2017 through December 2018, with follow-ups of at least two-year duration. The effectiveness of immunomodulators on keratitis and uveitis was studied. The following drugs were used: Hebertrans, human gamma globulins at 10 % and the combination of this with levamisole or Hebertrans.Results: treatments were effective in 89,58 % of overall cases, reaching 92,86 % in posterior uveitis. Ten patients could not be controlled, half of them with herpetic keratitis. 61,46 % were treated with Hebertrans, which was effective in 89,83 %. 87,46 % of the patients with herpetic keratitis were controlled with Hebertrans and 90,91 % of the patients suffering from uveitis with human gamma globulins.Conclusions: the use of immunomodulators in patients with chronic eye disorders was described. Hebertrans, single gamma globulin or its combinations were effective.

Integrin regulation by Rap1 is indispensable for lymphocyte recirculation. In mice having B-cell-specific Rap1a/b double knockouts (DKO), the number of B cells in lymph nodes decreased to approximately 4% of that of control mice, and B cells were present in the spleen and blood. Upon the immunization with NP-CGG, DKO mice demonstrated the defective GC formation in the spleen, and the reduced NP-specific antibody production. In vitro, Rap1 deficiency impaired the movement of activated B cells along the gradients of chemoattractants known to be critical for their localization in the follicles. Furthermore, B-1a cells were almost completely absent in the peritoneal cavity, spleen and blood of adult DKO mice, and the number of B-cell progenitor/precursor (B-p) were reduced in neonatal and fetal livers. However, DKO B-ps normally proliferated, and differentiated into IgM+ cells in the presence of IL-7. CXCL12-dependent migration of B-ps on the VCAM-1 was severely impaired by Rap1 deficiency. Immunostaining study of fetal livers revealed defects in the co-localization of DKO B-ps and IL-7-producing stromal cells. This study proposes that the profound effects of Rap1-deficiency on humoral responses and B-1a cell generation may be due to or in part caused by impairments of the chemoattractant-dependent positioning and the contact with stromal cells.

Rationale: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1 year after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment. Patient concerns: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units. Diagnoses: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed. Interventions: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin. Outcomes: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative. Lessons: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner.

Antibody-mediated diseases affect more than 10% of the human population. For most, no cure is available, particularly when the pathogenic antibodies are secreted by long-lived plasma cells resistant to conventional immunosuppressive therapies. Current therapeutic approaches target not only the plasma cells that secrete pathogenic antibodies, but also those providing protective antibodies. Here, in a murine model bearing long-lived plasma cells secreting anti-OVA and -chicken gamma globulin (CGG) antibodies, we describe the first-time use of an antigen-antibody (OVA/anti-CD138 antibody) conjugate for in vivo labeling and selective ablation of plasma cells that secrete antibodies specific for the antigen OVA. The selective depletion also led to a stable reduction of the corresponding serum anti-OVA antibody levels. In contrast, CGG-specific plasma cells and circulating anti-CGG antibody levels remained unchanged. The method described here should enable the development of unique causative treatment strategies for established antibody-mediated diseases sparing humoral immunity.

During the early 1950s, Canada’s efforts to prevent polio became heavily influenced by developments in the United States. America’s foremost polio charity, the National Foundation for Infantile Paralysis, sponsored University of Pittsburgh researcher Dr. William McD. Hammon to evaluate the efficacy of a human blood fraction, gamma globulin (GG), to prevent paralytic polio. When the resulting clinical trial data appeared to show that the blood fraction offered some protection against the disease, Canadians embraced the concept for reasons of historical trust, parental demand, and public health pragmatism. They established Canada’s first national immunization program to fight polio before the vaccine, as well as developed a plan to produce, evaluate, and distribute GG to epidemic areas. Despite being an expensive enterprise for a geographically vast and sparsely populated nation, Canada’s GG program was extended to citizens and it became an important response to polio before a safe and effective vaccine was licensed. Although the blood fraction was not as effective at preventing polio paralysis as researchers had anticipated, its systematic use reveals how Canadian health leaders drew on transnational relationships to reduce the incidence of disease.

Densitometric quantitation using serum protein electrophoresis (SPE) is used to monitor monoclonal proteins (M-proteins) in human patients but has not been validated in the dog. Serum globulin concentrations, species-specific radial immunodiffusion (RID), and ELISAs are currently used in veterinary medicine.We aimed to compare four methods that quantify M-proteins using densitometry and biuret protein (dM-protein) measurements. We also validated the best performing method and compared it with the RID and ELISA methods for measuring canine serum M-protein.Serum from six normal dogs and 83 serum samples from 46 dogs with confirmed monoclonal gammopathies were used. A spike and recovery experiment with purified monoclonal IgG and IgM, inter-run and intra-run variability, linearity under dilution, and lower limit of detection were performed. Results of commercial canine RID and ELISA kits for total class-specific immunoglobulin were compared with dM-proteins.The corrected perpendicular drop gating method had20% error for IgG/γ-globulin and IgM/β-globulin M-protein quantifications. Linearity (r .99), intra-run CV (1.1%-2.3%), and inter-run CVs (2.0%-3.5%) were acceptable. Correlation between the RID and densitometry results ranged from r = .25 to r = .88, depending on the class. The RID result was greater than that of the biuret total protein in 26/63 (41%) IgA cases. A panel of IgG, IgA, and IgM RIDs failed to correctly identify an IgM paraproteinemia in 6/6 (100%) cases. Densitometry was not comparable with any other tested method.Densitometric quantitation is a valid technique for measuring M-proteins in the β- and γ-globulin regions. Immunotyping via RID using the tested kit does not appear to detect IgM. Densitometry is recommended for measuring M-proteins in canine patients.

Communicated by Ramaswamy H. Sarma.

Immunoglobulin A nephropathy (IgAN) is characterized by mesangial IgA and IgG co-deposition. As the clinical course of IgAN is highly variable, a lot of patients will eventually develop to end-stage renal disease (ESRD) within years. Hirudin, a potent and specific thrombin inhibitor, has been reported to treat IgAN with hematuria, but the mechanism is unclear. Our study aims to explore the potential of hirudin and the underlying mechanism in the treatment of IgAN. The establishment of IgAN model was set up in rats through oral and intravenous immunization with bovine gamma-globulin (BGG). Results suggested that hirudin could reduce the increased level of proteinuria, serum creatinine and urea nitrogen in IgAN models. Besides that, hirudin ameliorated the elevated number of apoptotic bodies and expressions of apoptosis-related proteins (caspase-3 and caspase-9) in IgAN model. The fibrosis indexes (transforming growth factor β-1 (TGF-β1), Collagen-IV (CoI-IV) and Fibronectin-1) of kidney were remarkably suppressed in IgAN rats treated with hirudin compared with IgAN rats with no further treatment. IgAN rats exhibited remarkably increased inflammatory factors (IL-1β, IL-6, and IL-18), while hirudin treatment significantly alleviated these alterations. Moreover, the reduced levels of CD4+CD25+Foxp3+ Treg and CD4+IFN-γ+ Th1/CD4+IL-4+ Th2 could be reversed by hirudin in IgAN model. Furthermore, in the process of IgAN, hirudin could inactivate various pathways (IκBα, NF-κB, TNF-α, and VCAM-1) compared with IgAN model group. Taken together, our study indicated that hirudin could ameliorate IgAN through suppressing fibrosis and inflammatory response. These findings provide a new therapeutic method to treat IgAN.

OBJECTIVE: Diffuse large B-cell lymphoma can complicate the course of B-cell primary immunodeficiencies or induce lowering of total gamma globulin levels, whose clinical status as an effective secondary immunodeficiency remains unspecified. This study aimed to assess the frequency, and clinical and prognostic relevance of the low total gamma-globulin levels discovered at diagnosis of diffuse large B-cell lymphoma. RESULTS: In a 2-year monocentric retrospective study, 96 patients diagnosed with diffuse large B-cell lymphoma who had a serum electrophoresis were included. Patients were divided into those with lower (L-TGL and higher (H-TGL) total gamma-globulin levels (total gamma-globulin levels ≤5.5 g/l and >5.5 g/l) and compared for outcomes, including fatal infectious events. Twelve (12.5%; 8 males; age median 68 years, range 55—82 years) exhibited L-TGL. There was no difference between the both groups regarding demographics, Ann Arbor lymphoma stage, inflammatory parameters or chemotherapy regimen. However, overall death rates (10/12, 83.3% versus 22/96, 26.2%; p = 0.03) and infection-related death rates (10/12, 83% versus 6/96, 6.2%; p

BACKGROUND Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide, and scientists are trying to find a way to overcome the disease. We explored the risk factors that influence patient outcomes, including treatment regimens, which can provide a reference for further treatment. MATERIAL AND METHODS A retrospective cohort study analysis was performed using data from 97 patients with COVID-19 who visited Wuhan Union Hospital from February 2020 to March 2020. We collected data on demographics, comorbidities, clinical manifestations, laboratory tests, treatment methods, outcomes, and complications. Patients were divided into a recovered group and a deceased group. We compared the differences between the 2 groups and analyzed risk factors influencing the treatment effect. RESULTS Seventy-six patients recovered and 21 died. The average age and body mass index (BMI) of the deceased group were significantly higher than those of the recovered group (69.81±6.80 years vs 60.79±11.28 years, P

Synthetic hydrogels with the ability to recognize and bind target proteins are useful for a number of applications, including biosensing and therapeutic agent delivery. One popular method for fabricating recognitive hydrogels is molecular imprinting. A long-standing hypothesis of the field is that these molecularly imprinted polymers (MIPs) retain the chemical and geometric profile of their protein template, resulting in subsequent ability to recognize the template in solution. Here, we systematically determined the influence of network composition, as well as the identity, amount, and extraction of imprinting templates, on the protein binding of MIPs. Network composition (i.e. the relative number of ionizable and hydrophobic groups) explained the extent of protein adsorption in all cases. The identity and amount of imprinting template, albeit a protein or synthetic polymer (PEG) of similar molecular weight, did not significantly influence the amount of protein bound. While the purification method influenced the extent of template adsorption, it did so by chemically modifying the network (acrylamide hydrolysis, increasing the acid content by up to 21%) and not by voiding occupied MIP pores. Therefore, our results indicate that material composition determines the extent to which MIPs bind template and non-template proteins.

Animal models recapitulating distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. The precise mechanisms of lethality in this mouse model remain unclear. Here, we evaluated the spatiotemporal dynamics of SARS-CoV-2 infection for up to 14 days post-infection. Despite infection and moderate pneumonia, rapid clinical decline or death of mice was invariably associated with viral neuroinvasion and direct neuronal injury (including brain and spinal neurons). Neuroinvasion was observed as early as 4 dpi, with virus initially restricted to the olfactory bulb supporting axonal transport via the olfactory neuroepithelium as the earliest portal of entry. No evidence of viremia was detected suggesting neuroinvasion occurs independently of entry across the blood brain barrier. SARS-CoV-2 tropism was not restricted to ACE2-expressing cells (e.g., AT1 pneumocytes), and some ACE2-positive lineages were not associated with the presence of viral antigen (e.g., bronchiolar epithelium and brain capillaries). Detectable ACE2 expression was not observed in neurons, supporting overexpression of ACE2 in the nasal passages and neuroepithelium as more likely determinants of neuroinvasion in the K18-hACE2 model. Although our work incites caution in the utility of the K18-hACE2 model to study global aspects of SARS-CoV-2 pathogenesis, it underscores this model as a unique platform for exploring the mechanisms of SARS-CoV-2 neuropathogenesis that may have clinical relevance acknowledging the growing body of evidence that suggests COVID-19 may result in long-standing neurologic consequences.IMPORTANCECOVID-19 is predominantly a respiratory disease caused by SARS-CoV-2 that has infected more than 191 million people with over 4 million fatalities (2021-07-20). The development of animal models recapitulating distinctive features of severe COVID-19 is critical to enhancing our understanding of SARS-CoV-2 pathogenesis and in the evaluation of vaccine and therapeutic efficacy. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. Here, we show lethality of this model is invariably associated with viral neuroinvasion linked with viral replication and assembly. Importantly, pneumonia albeit invariably present was generally moderate with the absence of culturable infectious virus at peak neuroinvasion. The dynamics of viral neuroinvasion and pneumonia were only partially dependent on hACE2. Overall, this study provides an in-depth sequential characterization of the K18-hACE2 model following SARS-CoV-2 infection, highlighting its significance to further study the mechanisms of SARS-CoV-2 neuropathogenesis.

Background Dogs are the main reservoir hosts of Leishmania infantum; nevertheless, recent investigations indicate a likely role for cats in the epidemiology of Leishmania infection. Feline leishmaniosis (FeL) remains poorly characterised, partly due to the lack of suitable diagnostic tools. This study aimed to compare serum amyloid A (SAA) levels and serum protein electrophoresis (SPE) profiles (specifically, alpha 2 and gamma globulins) in cats naturally exposed to or infected by L. infantum from southern Italy versus those of healthy controls and versus cats with neoplastic or inflammatory conditions from non-endemic areas. Methods Serum or plasma samples from four cohorts of cats were analysed for SAA levels and by SPE: (i) G1: healthy controls from Leishmania-non-endemic regions of Switzerland; (ii) G2: cats pre-diagnosed with neoplastic or inflammatory conditions available from the University of Cambridge sample archive; (iii) G3: L. infantum-seropositive, quantitative (q)PCR-negative cats from southern Italy; (iv) G4: L. infantum-seropositive and qPCR-positive cats from southern Italy. SAA data were assessed for normality and homoscedasticity using the Shapiro–Wilk and Levene’s tests, respectively; the Kruskall–Wallis test, followed by Dunn’s test with Bonferroni correction were subsequently used to compare SAA serum levels between groups. A weighted generalised linear model with a binomial distribution was used to assess statistically significant differences in the numbers of animals displaying elevated gamma globulins and increased alpha 2 globulins between groups. Results Overall, 68 samples were analysed (G1: n = 16, G2: n = 20, G3: n = 20, G4: n = 12). Cats suffering from neoplastic and inflammatory conditions (G2 ) showed significantly higher SAA levels than healthy controls (G1) (median values [interquartile range]: G1: 0.00 [0.00–0.00] mg/l versus G2: 0.85 [0.00–49.55] mg/l). G2, G3 and G4 cats showed higher percentages of individuals with increased alpha 2 globulins (percentages ± standard error: G1 = 20.0% ± 10.3, G2 = 80.0% ± 8.9, G3 = 70.0% ± 10.2, G4 = 75.0% ± 12.5) and gamma globulins (G1 = 0.0% ± 0, G2 = 65.0% ± 10.7, G3 = 50.0% ± 11.2, G4 = 58.3% ± 14.2) than healthy control cats (G1). For all three markers, no significant difference between cats within G2, G3 and G4 was recorded. Conclusions This study indicates that the proportions of animals with elevated levels of alpha 2 and gamma globulins are significantly higher in cats exposed to and infected with L. infantum. Levels of SAA and alpha 2 and gamma globulins may not be used to differentiate between L. infantum infection or exposure, and neoplastic and/or inflammatory conditions. Graphical Abstract

The aetiology of febrile exanthems in children is often difficult to distinguish clinically. A diagnosis of Kawasaki disease (KD) should be considered in infants with exanthematous fever. More perplexing is the increasing incidence of an atypical form of KD. Pathogenesis of KD remains unclear even though an aberrant response of the immune system to an unidentified pathogen is often hypothesised. A 30-fold increase in the incidence of KD in Italy during the SARS-CoV-2 pandemic suggests an immune response to a viral trigger. We report an infant clinically diagnosed with high probability as incomplete KD, who presented with reactivation of the BCG injection site even though fever with rash was only less than 3 days duration. Echocardiography confirmed coronary artery abnormalities and prompt treatment with intravenous immunoglobulin facilitated rapid recovery. Physicians should consider a diagnosis of KD if BCG site reactivation is noted in children presenting with febrile exanthema.

This research paper addresses the hypothesis that an oral supplementation with organically modified clinoptilolite will improve colostrum quality in primiparous dairy cows whilst having no adverse effects on the cows' health. A total of 36 pregnant Holstein primiparous dairy cattle were randomly assigned to receive daily oral drenching, two hours following morning feeding, with 1 l of water containing either 0 g/l (n = 16) or 150 g/l (n = 20) of clinoptilolite. Treatment lasted from 24 ± 4 d prior to expected parturition until two days postpartum (pp). Colostrum was collected at 2 to 3 h, 12, 24 and 36 h pp and blood samples were collected at 24 ± 4 and 4 ± 2 d prior to parturition and 1, 2 and 7 d pp. Overall mean dry matter, fat and total protein percentage as well as IgG concentration and mass were significantly greater in colostrum collected from cattle drenched with clinoptilolite (total protein increased by 15% and IgG concentration and mass by 21 and 38% respectively at first sampling and further at second sampling). Total γ globulin and most other blood serum biochemistry parameters did not differ between cattle treated and not treated with clinoptilolite, the only exception being the fast anionic γ globulin fraction that was 17% greater at 4 ± 2 d prior to parturition and 10% lower on the 1st day pp in treated cattle. These results showed that organically modified oral clinoptilolite supplementation at 150 g/d significantly increases the IgG concentration in colostrum and has no adverse effects on the energy status, protein, lipid, and mineral metabolism in primiparous dairy cattle during prepartum period.

In this study, the interaction between gold nanoparticles (AuNPs) and proteins (including lysozyme, trypsin, pepsin, γ-globulin and hemoglobin) was investigated by UV-visible absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy and protein activity assay. AuNPs was synthesized using reduction of HAuCl

To determine the curative effect of gamma globulin combined with methylprednisolone sodium succinate on paediatric patients with severe hand-foot-mouth disease and analyse its influence on cardio-pulmonary functions.Eighty paediatric patients with severe hand-foot-mouth diseases (HFMD) treated in Baoding Children's Hospital, Key Laboratory of Clinical Research on Respiratory Digestive Disease from January 2015 to January 2017 were selected. This study was designed as a case control study with equally dividing patients into test and control groups through random digital method. Patients in the control group accepted methylprednisolone sodium succinate treatment based on conventional therapy. Those in the test group accepted gamma globulin combined with methylprednisolone sodium succinate. The efficacy of the two groups were observed and compared and the improvement of cardiac function index was detected after 3 days of treatment.The time for symptom remission and hospitalisation of children in the test group were significantly shorter than those in the control group (P0.05). The differences between the two groups had no statistical significance in terms of PaO2, PaCO2, OI, HR, EF% and CO before treatment. After the treatment, patients in the test group had significant improvement compared with the control group (P0.05).Curative effect of gamma globulin combined with methylprednisolone sodium succinate on paediatric patients showed significance and this treatment could be effectively improve clinical symptoms and cardio-pulmonary functions of paediatric patients.

Background Henoch‐Schonlein purpura nephritis (HSPN) is a serious complication of Henoch‐Schonlein purpura (HSP), which is usually treated with immunosuppressant and glucocorticoid. This study was designed to explore the effect of dexamethasone and gamma globulin combined with prednisone in the treatment of pediatric HSPN. Methods According to the treatment plan, 60 children treated with dexamethasone and gamma globulin were included in the control group, and the rest 55 children treated with dexamethasone and gamma globulin combined with prednisone were selected as the research group. The clinical manifestations, therapeutic effect, immune function, serum inflammatory factors, blood coagulation function, urine routine, renal function, and adverse reactions were compared between the two groups. Results The clinical manifestations of children in the research group were significantly better than those in the control group after treatment (P, Comparison of immune function indexes between the two groups before and after treatment. A, After treatment, the CD3+ level of children in both groups increased, and its change in the research group was more obvious than that in the control group. B, After treatment, the CD4+ level of children in both groups elevated, and its change in the research group was more significant than that in the control group. C, After treatment, the CD8+ level of children in both groups increased, and its change in the research group was more significant than that in the control group. D, After treatment, the ratio of CD4+/CD8+ decreased in both groups, and the change in the research group was more significant than that in the control group. E, After treatment, the IgA level of the two groups of children declined, and the IgA level in the research group changed more significantly than that in the control group. Note: * represents the comparison between the two groups, P

Physical review letters 126(13), 138004 (2021). doi:10.1103/PhysRevLett.126.138004, While the interplay between liquid-liquid phase separation (LLPS) and glass formation in biological systems is highly relevant for their structure formation and thus function, the exact underlying mechanisms are not well known. The kinetic arrest originates from the slowdown at the molecular level, but how this propagates to the dynamics of microscopic phase domains is not clear. Since with diffusion, viscoelasticity, and hydrodynamics, distinctly different mechanisms are at play, the dynamics needs to be monitored on the relevant time and length scales and compared to theories of phase separation. Using x-ray photon correlation spectroscopy, we determine the LLPS dynamics of a model protein solution upon low temperature quenches and find distinctly different dynamical regimes. We observe that the early stage LLPS is driven by the curvature of the free energy and speeds up upon increasing quench depth. In contrast, the late stage dynamics slows down with increasing quench depth, fingerprinting a nearby glass transition. The dynamics observed shows a ballistic type of motion, implying that viscoelasticity plays an important role during LLPS. We explore possible explanations based on the Cahn-Hilliard theory with nontrivial mobility parameters and find that these can only partially explain our findings., Published by APS, College Park, Md.

Background The causative virus of coronavirus disease 2019 (COVID-19) may cause severe fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to acute renal injury due to COVID-19 in patients who have undergone renal transplantation are scarce. We herein report two cases of COVID-19 along with acute kidney injury following kidney transplantation. Case presentation: Two patients with COVID-19 underwent renal transplantation and were subsequently diagnosed with acute kidney injury. The first patient presented with progressive respiratory symptoms and acute renal injury. He was treated with diuretics and suspension of immunosuppressive therapy; however, the patient died. The second patient presented with respiratory tract symptoms, hypoxemia, and progressive deterioration of renal function followed by improvement. Her mycophenolate mofetil was stopped after admission, and tacrolimus was discontinued 10 days later. Moxifloxacin and methylprednisolone were continued in combination with albumin and gamma globulin infusion. A diuretic was administered, and prednisone was gradually reduced along with tacrolimus. The patient exhibited a satisfactory clinical recovery. Conclusion Patients who develop COVID-19 after kidney transplantation are at risk of acute kidney injury, and their prednisone, immunosuppressant, and gamma globulin treatment must be adjusted according to their condition.

Polymer-grafted media have been a focus of recent development for ion exchange chromatography (IEC) because of their capacity and uptake kinetics that can lead to high dynamic capacity in protein purification. This work is devoted to developing novel cation exchangers of high adsorption performance by grafting polymerization of sodium methacrylate (MA) onto a commercial agarose gel Sepharose FF (FF). Five polyMA (pMA)-grafted FF gels were prepared with the same grafting density but different chain lengths (i.e., different ionic capacities, ICs), and named as FF-pMA-IC (IC denotes IC value in mmol/L). The effects of chain length (IC) and ionic strength (IS) on protein adsorption and chromatographic behaviors were examined using lysozyme (at pH 8.0) and γ-globulin (at pH 5.0) as model proteins. It was found that lysozyme adsorption capacity increased with increasing IC till reaching a plateau (390 mg/mL) over IC=540 mmol/L (FF-pMA-540), while there was an optimum IC (320 mmol/L, FF-pMA-320) at which γ-globulin adsorption capacity reached the highest (208 mg/mL). With increasing chain length (IC), the uptake rates of both the proteins presented decreasing trends due to the steric hindrance caused by the polymer chains. At the same IC, however, the uptake rate of lysozyme was much higher than that of γ-globulin because of the different sizes of the two proteins. Increasing salt concentration obviously promoted the uptake rates of the proteins, which led to the increase of dynamic binding capacities (DBCs) in different salt concentration ranges. The DBC value of lysozyme on FF-pMA-540 kept as high as 108-198 mg/mL in the salt concentration range of 0-150 mmol/L, and the DBC of γ-globulin on FF-pMA-320 increased to 27 mg/mL with increasing salt concentration from 100 mmol/L. This work clearly indicated the presence of optimal IC values (chain lengths) for different sized proteins, and IS was also crucial for reaching a high DBC for a specific protein. The findings provided insight into the selection of FF-pMA-n gels and operational conditions (e.g., IS) for the purification of a target protein of defined size.

The present work is aimed at investigating the chemicophysical properties of the interface between silicone oils (SOs) used in vitreoretinal surgery and aqueous solutions, in the presence of surfactant biomolecules. Such molecules are thought to play an important role in the formation of SO emulsions in vitrectomised eyes, in which the natural vitreous body has been replaced with a SO. In particular, we have measured the interfacial tension (IT) and the interfacial dilational viscoelasticity (DV) of the interface between SO (Siluron 1000) and serum proteins (albumin and γ-globulins) at various concentrations in a Dulbecco alkaline buffer. The equilibrium IT value is relevant for the onset of emulsification, and the DV influences the stability of an emulsion, once formed. The study is complemented by preliminary emulsification tests. The experimental results show that, when proteins are dissolved in the aqueous solution, the rheological properties of the interface change. The IT decreases significantly for physiological protein concentrations, and the DV modulus achieves high values, even for small protein concentrations. The emulsification tests confirm that, in the presence of proteins, emulsions are stable on the time scale of months. We conclude that the measured values of IT in the presence of serum proteins are compatible with the promotion of droplet formation, which, in addition, are expected to be stable against coalescence. Adsorption of biomolecules at the interface with the SO is, therefore, likely to play an important role in the generation of an emulsion in eyes subjected to vitrectomy. These findings are relevant to identify strategies to avoid or control the formation of emulsions in eyes.

OBJECTIVE: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. RESULTS: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. CONCLUSION: The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.

To explore the curative effects of vancomycin and cefotaxime combined with gamma globulin respectively in neonatal septicemia and their influences on PCT, CRP, and hs-CRP, so as to provide references for clinical treatment.181 patients with neonatal septicemia admitted to Huangshi Maternity and Child Health Hospital from April 2012 to August 2014 were selected as the study subjects. Patients treated with vancomycin combined with gamma globulin were selected as group A (96 cases) and those treated with cefotaxime combined with gamma globulin were selected as group B (85 cases). The improvement time of clinical symptoms (milk rejection, nervous system symptoms, body temperature), hospital stays, mortality, medicine curative effects, adverse reactions, complications, and levels of serum CRP, PCT, and hs-CRP of patients before and after treatment were compared between the two groups.The improvement time of clinical symptoms like body temperature, milk rejection, and neurological symptoms, as well as hospital stays in group A were lower than those in group B (p0.05); the total effective rate of medicine curative effects in group B was better than that in group A (p0.05); there was no significant difference in levels of serum CRP, PCT, and hs-CRP between the two groups before treatment (p0.05); after treatment, levels of serum CRP, PCT, and hs-CRP in both groups decreased significantly, and levels of serum CRP, PCT, and hs-CRP in group B decreased more significantly than those in group A (p0.05).Cefotaxime combined with gamma globulin in the treatment of patients with neonatal septicemia has short improvement time in clinical symptoms, high total effective rate of drugs, low mortality, fewer adverse reactions and complications, and can significantly reduce levels of serum CRP, PCT, and hs-CRP, which is worthy of further promotion and application in clinical practice.

C-reactive protein (CRP) is encoded by CRP or PTX1 gene and procalcitonin (PCT) is produced by the CALC-1 gene induction. Both PCT and CRP are known as valued biomarkers markers in prediction of Serious Bacterial Infections (SBI) in children. This experiment carried out to analyze the efficacy of cefotaxime combined with gamma globulins on neonatal sepsis and the effect on CRP and PCT. For this purpose, a total of 120 sepsis children were selected and randomly divided into observation and control groups. Children in the control group were treated with cefotaxime, while children in the observation group were treated with cefotaxime combined with gamma globulins. The two groups were compared in terms of the relative measures of efficacy, the total effective rate of treatment, the incidence of complications and serum CRP and PCT levels before and after treatment. The clinical measures of the observation group were all lower than those of the control group, and the total effective rate of the treatment was higher than that of the control group, while the incidence of complications was lower than that of the control group. In addition, before treatment, there was no difference in CRP and PCT between the two groups; after treatment, the above measures in the observation group were lower than those in the control group. It is concluded that Cefotaxime combined with gamma globulins in the treatment of neonatal sepsis has significant efficacy and is clinically more effective than cefotaxime monotherapy. This combination can shorten clinical symptom remission time and hospital stay, improve serum CRP and PCT levels and promote the recovery of children, worthy of promotion.

Total knee arthroplasty has become a routine procedure for patients suffering from joint diseases. Although the number of operations continuously increases, a limited service-life of implants represents a persisting challenge for scientists. Understanding of lubrication may help to suitably explain tribological processes on the way to replacements that become durable well into the third decade of service. The aim of the present study is to assess the formation of protein lubricating film in the knee implant. A developed knee simulator was used to observe the contact of real femoral and transparent polymer tibial component using fluorescent microscopy. The contact was lubricated by various protein solutions with attention to the behaviour of albumin and γ-globulin. In order to suitably mimic a human synovial fluid, hyaluronic acid and phospholipids were subsequently added to the solutions. Further, the change in shape and the migration of the contact zone were studied. The results showed considerable appearance differences of the contact over the swing phase of the simplified gait cycle. Regarding film formation, a strong interaction of the various molecules of synovial fluid was observed. It was found that the thickness of the lubricating layer stabilizes within around 50 s. Throughout the contact zone, protein agglomerations were present and could be clearly visualised using the applied optical technique.

The adsorption of c-globulin was evaluated with experiments with silica particles marketed as Syloid AL1-FP (SAL), XDP-3150 (SXDP), and 244FP (SFP). The influence of pH, pore sizes, and degree of surface porosity on the extent of c-globulin immobilization was examined. Protein adsorption on these particles was largely related to their surface porosity and pore sizes. The adsorption capacity was established to be greater with mesoporous SFP and SXDP particles at 474 and 377 mg/g, respectively, when compared to significantly low-porosity SAL (16 mg/g). Additionally, c-globulin immobilization was favored at pH closer to iso-electric point. A key aim of this work was to better understand and improve the limited reversibility of protein adsorption. Protein desorption was found to be lower in simulated intestinal fluid (SIF) in comparison to pH 7.4 phosphate buffer (PB). The use of displacer molecules (sodium dodecyl sulfate [SDS]/Tween 80/Pluronic F127 [PF127]) promoted protein desorption from the adsorbent surface by the exchange mechanism. The PF127 provided substantial release in both studied condition but the highest release of 83% of c-globulin from SXDP was obtained with tween 80 in PB. The released protein was analyzed with circular dichroism (CD) spectroscopy which indicated that the secondary structure of desorbed c-globulin was dependent on the pH and displacer molecule. The conformation largely remained unchanged when desorption was carried out in SIF but changed markedly in PB specially in the presence of SDS.