Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis

Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don’t have such an effective anticancer effect even at extremely high concentrations. Proteomic and transcriptomic analyses reveal this direct cytotoxicity is derived predominantly from Ab-mediated phagocytosis. High affinity immunoglobulin gamma Fc receptor I shows differential up-regulation in gastric cancer cells treated by these nanodrugs compared with Ab, especially for Ab with gold nanorods. Simplified and powerful designs of smart nanoparticles are highly desired for clinical application. The enhancement of Ab accumulation with a simple composition, combined with direct cytotoxic effects specific to cancer cells brought improved therapeutic effects in vivo compared with Ab, which can promote further clinical application of gold nanomaterials in the diagnosis and therapeutics of gastric cancer.

Cerebrospinal fluid oligoclonal immunoglobulin gamma bands and long-term disability progression in multiple sclerosis: a retrospective cohort study

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. In this study, we aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, age at MS onset, and time to sustained Expanded Disability Status Scale (EDSS) milestones 3, 4, and 6; time to conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. The OCB-positive group reached disability milestones at an earlier time and younger age. OCB-positivity significantly increased the risk of reaching EDSS 3.0 (HR = 1.29, 95% CI 1.12 to 1.48, P < 0.001) and 4.0 (HR = 1.38, 95% CI 1.17 to 1.63, P < 0.001). The OCB-positive group had a 20% higher risk of conversion to SPMS. CSF-OCB presence is associated with higher risk of reaching EDSS milestones and conversion to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

Cerebrospinal Fluid Oligoclonal Immunoglobulin Gamma Bands and Long-term Disability Progression in Multiple Sclerosis: a Retrospective Cohort Study

Multiple sclerosis (MS) patients with and without the oligoclonal band (OCB) distribution of immunoglobulin gamma (IgG) in the cerebrospinal fluid (CSF) has a different genetic background and brain MRI features. In this study we have aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, MS onset and date at sustained Expanded Disability Status Scale (EDSS) score milestones 3, 4, 6, date at conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. The OCB-positive group reached disability milestones at earlier time and at younger age. OCB-positivity significantly increased the risk of reaching EDSS score 3.0 (HR=1.29, 95%CI: 1.12 to 1.48, P<0.001) and 4.0 (HR= 1.38, 95%CI: 1.17 to 1.63, P<0.001). The OCB-positive group had a 20 % higher risk to convert to SPMS. CSF-OCBs presence is associated with higher risk to reach EDSS milestones and to convert to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

Oligoclonal Immunoglobulin Gamma Bands and Long-Term Disability Progression in Multiple Sclerosis: A Retrospective Cohort Study

Background Multiple sclerosis (MS) patients without the typical oligoclonal bands (OCB) distribution of immunoglobulin gamma (IgG) in the cerebrospinal fluid (CSF) has a different genetic background and brain MRI features than OCB-positive MS patients. It is less clear if OCB presence indicates differences in clinical aspects of MS. Objective To determine whether CSF OCB status is associated with long-term disability outcomes. Methods We used Swedish MS register data on clinically definite MS patients with known OCB status. Date of birth, MS onset and date at sustained Expanded Disability Status Scale (EDSS) score milestones 3, 4, 6, date at conversion to secondary progressive (SP) MS, sex, and immunomodulatory treatment (IMTs) duration were collected. Multivariate Cox regression models were used to investigate the association between OCB status and risk of reaching each milestone. Results The OCB-positive group reached disability milestones at an earlier time and at younger age. OCB positivity significantly increased the risk of reaching EDSS score 3.0 (HR = 1.29, 95%CI: 1.12 to 1.48, P < 0.001) and 4.0 (HR = 1.38, 95%CI: 1.17 to 1.63, P < 0.001) but non-significantly for EDSS 6. The OCB-positive group had a 20 % higher risk to convert to SPMS. Conclusion Patients with or without CSF OCBs share a risk of long term progression and for conversion to SPMS. Presence of OCBs in the CSF is associated with higher risk to reach EDSS milestones and a higher risk to convert to SPMS. Our findings suggest higher disease modifying effect of OCB presence in the early inflammatory stages of MS.

Mechanism of Intestinal Flora and Proteomics on Regulating Immune Function of Durio zibethinus Rind Polysaccharide

In this study, cyclophosphamide was injected intraperitoneally to establish an immunosuppressive mouse model to study the immune regulating effects of Durio zibethinus Murr rind polysaccharide (DZMP) through proteomics and intestinal flora. The results showed that the thymus and spleen indexes of the high-dose DZMP (200 mg/kg) group were significantly increased, and the tissue structure of the spleen was improved compared with the model group ( P < 0.01 ). The contents of IL-2, IL-4, IL-6, and TNF-α in the high-dose group of DZMP were significantly increased ( P < 0.001 ). Activities of acid phosphatase (ACP), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) were increased in serum ( P < 0.01 ). In the liver, catalase (CAT) activity was increased ( P < 0.001 ) while the malondialdehyde (MDA) content was decreased and immune activity was increased ( P < 0.001 ). Proteomics studies showed that the drug group could significantly increase the low-affinity immunoglobulin gamma Fc receptor III (FcγRIII) protein and protein kinase C-α (PKC-α) compared with the model group ( P < 0.001 ). In addition, the result showed that those proteins were likely involved in the regulation of the metabolic pathways of autoimmune thyroid disease, Staphylococcus aureus infection, and NF-κB signaling pathway. Intestinal microbial studies showed that short-chain fatty acid (SCFA) content was increased as well as the relative abundance of beneficial bacteria Akkermansia, Bacteroides, and Paraprevotella, while the relative abundance of Ruminococcus and Oscillospira was decreased compared with the model group ( P < 0.001 ). The results showed that DZMP might play a beneficial role in immune regulation by improving intestinal flora.

Salivary Immunoglobulin Gamma-3 Chain C Is a Promising Noninvasive Biomarker for Systemic Lupus Erythematosus

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively; p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively; p < 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.

Correction to: The use of intravenous immunoglobulin gamma for the treatment of severe coronavirus disease 2019: a randomized placebo-controlled double-blind clinical trial

An amendment to this paper has been published and can be accessed via the original article.

Changes in Serum and Salivary Proteins in Canine Mammary Tumors

The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.