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ARP Rheumatology 2024Patients being on immunosuppressive treatment of any reason, along with other risk factors such as smoking and obesity, are vulnerable to be infected from SARS-CoV2. Aim... (Review)
Review
INTRODUCTION
Patients being on immunosuppressive treatment of any reason, along with other risk factors such as smoking and obesity, are vulnerable to be infected from SARS-CoV2. Aim of this report is to describe a case of a female patient under Rituximab therapy who experienced episodes of lung infection due to Severe Acute Coronavirus 2 (SARS-CoV-2 ) invasion although fully vaccinated.
CASE REPORT
A 50-year-old woman, with a past medical history of lupus nephritis on rituximab was diagnosed with lung infection due to SARS-CoV-2. Eight months later, following her last infusion of Rituximab (RTX), she developed moderate Coronavirus Disease 2019 (COVID-19). After a partial recovery, she exhibited exacerbation of respiratory symptoms leading to readmission and invasive oxygenation. She was eventually discharged home after 31 days. Her monthly neurological evaluation did not reveal evidence of disease activity. She later received intravenous immunoglobulin and a decision was made to restart rituximab.
CONCLUSIONS
This case raises the possibility of persistent virus shedding and reactivation of severe acute respiratory syndrome coronavirus in a patient with SLE and Rituximab therapy. We emphasize a precise consideration of management of patients with autoimmune disorders during the COVID-19 pandemic.
Topics: Humans; Rituximab; Female; COVID-19; Middle Aged; Lupus Erythematosus, Systemic; SARS-CoV-2; COVID-19 Vaccines; Immunosuppressive Agents
PubMed: 38956996
DOI: No ID Found -
Molecular Oncology Jul 2024Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy.... (Review)
Review
Small cell lung cancer (SCLC) is a highly aggressive cancer with a dismal 5-year survival of < 7%, despite the addition of immunotherapy to first-line chemotherapy. Specific tumor biomarkers, such as delta-like ligand 3 (DLL3) and schlafen11 (SLFN11), may enable the selection of more efficacious, novel immunomodulating targeted treatments like bispecific T-cell engaging monoclonal antibodies (tarlatamab) and chemotherapy with PARP inhibitors. However, obtaining a tissue biopsy sample can be challenging in SCLC. Circulating tumor cells (CTCs) have the potential to provide molecular insights into a patient's cancer through a "simple" blood test. CTCs have been studied for their prognostic ability in SCLC; however, their value in guiding treatment decisions is yet to be elucidated. This review explores novel and promising targeted therapies in SCLC, summarizes current knowledge of CTCs in SCLC, and discusses how CTCs can be utilized for precision medicine.
PubMed: 38956984
DOI: 10.1002/1878-0261.13696 -
Drug Testing and Analysis Jul 2024ELISA assays are commonly used for drug screening by racing laboratories but are known to suffer from limited specificity. Inaccurate ELISA screening results are...
ELISA assays are commonly used for drug screening by racing laboratories but are known to suffer from limited specificity. Inaccurate ELISA screening results are typically produced by non-specific antibody interactions or by the retention of chromogenic material in the sample well due to sample degradation. While confirmation of drug positives can be achieved by mass spectrometry, the follow-up of inaccurate ELISA screening results represents an unnecessary cost in staff time and reagents. This is particularly true in the case of rhEPO screening using sandwich ELISA assays, where the confirmation method requires up to 3 days to perform. While most racing laboratories purchase commercial ELISA kits, these products can be customised to provide increased specificity for enhanced screening of positive samples. The specificity of commercial sandwich ELISA kits can be improved by a variety of mechanisms including the addition of competing analyte specific antibodies, substitution of capture antibodies or by performing ELISA analysis with and without capture antibodies. Non-specific signals in difficult matrices such as canine urine can also be reduced by the addition of BSA solutions to the ELISA plate prior to the addition of samples.
PubMed: 38956951
DOI: 10.1002/dta.3763 -
Oral Diseases Jul 2024High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from... (Review)
Review
OBJECTIVE
High-risk human papillomaviruses (HPV) are an established cause of oropharyngeal cancer. Their relationship with oral cancer remains unclear with detection ranging from 0% to 100%. HPV DNA detection or evidence of exposure alone is insufficient to conclude causality. This systematic review assesses the extent of bias in studies of HPV detection in cancers of the oral cavity.
METHODS
PubMed, Ovid MEDLINE, EMBASE, and PsycInfo databases were searched for observational studies reporting the effect of HPV in oral cavity specific cancers.
RESULTS
All 15 included studies presented HPV DNA detection or serum HPV-antibodies, none included mRNA E6/E7 analysis. Cases with oral cancer had 5.36 times (95% CI 3.29-8.72) higher odds of having HPV detected compared to controls. The odds of HPV detection were higher in cell-based (OR 6.93; 95% CI 0.82-58.55) and tissue samples (OR 5.28; 95% CI 3.41-8.18) than blood-based samples (OR 3.36; 95% CI 1.53-7.40).
CONCLUSION
When cancer site is clearly differentiated between oropharynx and oral cavity, 12 studies showed strong association between HPV and oral cancer, but the available estimates lack internal validity due to inconsistent measurements, high confounding, and lack of gold standard testing. There is not high-quality evidence to conclude a causal relationship of HPV with oral cancer.
PubMed: 38956902
DOI: 10.1111/odi.15062 -
Journal of Animal Physiology and Animal... Jul 2024The current research aimed to assess the effects of dietary macadamia oil (MO) on carcass traits, growth performance, physio-biochemical components, immune function,...
The current research aimed to assess the effects of dietary macadamia oil (MO) on carcass traits, growth performance, physio-biochemical components, immune function, thyroid hormones and inflammation markers of growing rabbits. A total of 96 growing rabbits were randomly distributed into four treatments, with 24 rabbits in each group. The rabbits were fed a basal diet (control group) or a diet supplemented with MO at 0.5 (MO0.5), 1 (MO1.0) and 2 (MO2.0) mL/kg of diet for eight weeks. The daily body weight gain and feed conversion ratio showed a quadratic improvement with increasing levels of MO, and the optimal dose was 1.25 mL/kg of diet. Increasing levels of MO also had a quadratic effect on hepatic and renal functions. Dose-response curves revealed that the optimal doses of MO were 1.50, 1.75 and 1.25 mL/kg of diet for total bilirubin, gamma-glutamyl transferase, and creatinine respectively. A quadratic relationship was observed between the increased levels of MO and tumour necrosis factor-α (p = 0.038), interleukin-6 (p = 0.014) and immunoglobulins (p = 0.016 and IgM p = 0.026). Additionally, a linear relationship was observed between the increment in MO levels and both nitric oxide (p = 0.040) and interleukin-4 (p = 0.001). The activities of superoxide dismutase and glutathione peroxidase showed a linear increase with increasing dietary MO content, while xanthine oxidase showed a linear decrease. Total antioxidant capacity showed quadratic improvement (p = 0.035) with the dietary treatment, with the optimal dose observed at 1.25 mL/kg of diet. The inclusion of MO in the diet had a linear effect on the activity of thyroxine (p = 0.001). Therefore, supplementation of MO at a dose of 1 or 1.5 mL/kg of diet in growing rabbits' diets can improve growth and carcass traits, sustain thyroid function by supporting immunity, and reduce oxidative/inflammation pathways.
PubMed: 38956882
DOI: 10.1111/jpn.14014 -
MAbs 2024Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in...
Early determination of potential critical quality attributes of therapeutic antibodies in developability studies through surface plasmon resonance-based relative binding activity assessment.
Precise measurement of the binding activity changes of therapeutic antibodies is important to determine the potential critical quality attributes (CQAs) in developability assessment at the early stage of antibody development. Here, we report a surface plasmon resonance (SPR)-based relative binding activity method, which incorporates both binding affinity and binding response and allows us to determine relative binding activity of antibodies with high accuracy and precision. We applied the SPR-based relative binding activity method in multiple forced degradation studies of antibody developability assessment. The current developability assessment strategy provided comprehensive, precise characterization of antibody binding activity in the stability studies, enabling us to perform correlation analysis and establish the structure-function relationship between relative binding activity and quality attributes. The impact of a given quality attribute on binding activity could be confidently determined without isolating antibody variants. We identified several potential CQAs, including Asp isomerization, Asn deamidation, and fragmentation. Some potential CQAs affected binding affinity of antibody and resulted in a reduction of binding activity. Certain potential CQAs impaired antibody binding to antigen and led to a loss of binding activity. A few potential CQAs could influence both binding affinity and binding response and cause a substantial decrease in antibody binding activity. Specifically, we identified low abundance Asn33 deamidation in the light chain complementarity-determining region as a potential CQA, in which all the stressed antibody samples showed Asn33 deamidation abundances ranging from 4.2% to 27.5% and a mild binding affinity change from 1.76 nM to 2.16 nM.
Topics: Surface Plasmon Resonance; Humans; Antibodies, Monoclonal; Antibody Affinity; Protein Binding; Animals
PubMed: 38956880
DOI: 10.1080/19420862.2024.2374607 -
European Journal of Medical Research Jul 2024Breast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift... (Review)
Review
Breast cancer (BC) has a high mortality rate and is one of the most common malignancies in the world. Initially, BC was considered non-immunogenic, but a paradigm shift occurred with the discovery of tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in the BC tumor microenvironment. CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) immunotherapy has emerged as a treatment option for BC, but it has limitations, including suboptimal antitumor effects and toxicity. Research has demonstrated that anti-CTLA-4 combination therapies, such as Treg depletion, cancer vaccines, and modulation of the gut microbiome, are significantly more effective than CTLA-4 monoclonal antibody (mAB) monotherapy. Second-generation CTLA-4 antibodies are currently being developed to mitigate immune-related adverse events (irAEs) and augment antitumor efficacy. This review examines anti-CTLA-4 mAB in BC, both as monotherapy and in combination with other treatments, and sheds light on ongoing clinical trials, novel CTLA-4 therapeutic strategies, and potential utility of biomarkers in BC.
Topics: Humans; CTLA-4 Antigen; Breast Neoplasms; Female; Immunotherapy; Tumor Microenvironment; Antibodies, Monoclonal; T-Lymphocytes, Regulatory; Lymphocytes, Tumor-Infiltrating
PubMed: 38956700
DOI: 10.1186/s40001-024-01901-9 -
BMC Veterinary Research Jul 2024The neuroimmune network plays a crucial role in regulating mucosal immune homeostasis within the digestive tract. Synaptosome-associated protein 25 (SNAP-25) is a...
BACKGROUND
The neuroimmune network plays a crucial role in regulating mucosal immune homeostasis within the digestive tract. Synaptosome-associated protein 25 (SNAP-25) is a presynaptic membrane-binding protein that activates ILC2s, initiating the host's anti-parasitic immune response.
METHODS
To investigate the effect of Moniezia benedeni (M. benedeni) infection on the distribution of SNAP-25 in the sheep's small intestine, the recombinant plasmid pET-28a-SNAP-25 was constructed and expressed in BL21, yielding the recombinant protein. Then, the rabbit anti-sheep SNAP-25 polyclonal antibody was prepared and immunofluorescence staining was performed with it. The expression levels of SNAP-25 in the intestines of normal and M. benedeni-infected sheep were detected by ELISA.
RESULTS
The results showed that the SNAP-25 recombinant protein was 29.3 KDa, the titer of the prepared immune serum reached 1:128,000. It was demonstrated that the rabbit anti-sheep SNAP-25 polyclonal antibody could bind to the natural protein of sheep SNAP-25 specifically. The expression levels of SNAP-25 in the sheep's small intestine revealed its primary presence in the muscular layer and lamina propria, particularly around nerve fibers surrounding the intestinal glands. Average expression levels in the duodenum, jejunum, and ileum were 130.32 pg/mg, 185.71 pg/mg, and 172.68 pg/mg, respectively. Under conditions of M. benedeni infection, the spatial distribution of SNAP-25-expressing nerve fibers remained consistent, but its expression level in each intestine segment was increased significantly (P < 0.05), up to 262.02 pg/mg, 276.84 pg/mg, and 326.65 pg/mg in the duodenum, jejunum, and ileum, and it was increased by 101.06%, 49.07%, and 89.16% respectively.
CONCLUSIONS
These findings suggest that M. benedeni could induce the SNAP-25 expression levels in sheep's intestinal nerves significantly. The results lay a foundation for further exploration of the molecular mechanism by which the gastrointestinal nerve-mucosal immune network perceives parasites in sheep.
Topics: Animals; Sheep; Sheep Diseases; Intestine, Small; Synaptosomal-Associated Protein 25; Enteric Nervous System; Rabbits
PubMed: 38956647
DOI: 10.1186/s12917-024-04140-6 -
Journal of Nanobiotechnology Jul 2024Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30...
BACKGROUND
Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins.
RESULTS
Four NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-β activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12-24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV.
CONCLUSION
The aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases.
Topics: Porcine respiratory and reproductive syndrome virus; Animals; Single-Domain Antibodies; Swine; Antigens, Differentiation, Myelomonocytic; Receptors, Cell Surface; Antigens, CD; Antibodies, Neutralizing; Peptides; Porcine Reproductive and Respiratory Syndrome; Mice; Virus Replication; Cell Line
PubMed: 38956618
DOI: 10.1186/s12951-024-02662-7 -
BMC Pulmonary Medicine Jul 2024Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to...
BACKGROUND
Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature.
CASE PRESENTATION
A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections.
CONCLUSIONS
To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.
Topics: Humans; Female; Myasthenia Gravis; Middle Aged; Bronchiolitis; Thymectomy; Thymus Neoplasms; Tomography, X-Ray Computed; Haemophilus Infections; Thymoma; Anti-Bacterial Agents; Taiwan
PubMed: 38956567
DOI: 10.1186/s12890-024-03134-2