Search Results (122)

Uncaria tomentosa (Ut) is a Rubiaceae widely used in Peru’s traditional medicine. It is mainly known by the vernacular name of Cat’s claw due to its morphological aspects and is found in tropical low mountain forests of Central and South America. A decoction of Ut bark, root and leaves is used traditionally for different health problems, including arthritis, weakness, viral infections, skin disorders, abscesses, allergies, asthma, cancer, fevers, gastric ulcers, haemorrhages, inflammations, menstrual irregularity, rheumatism, urinary tract inflammation and wounds, among others, which gave rise to scientific and commercial interest. The present paper reviews research progress relating to the ethnobotany, phytochemistry and pharmacology of Ut, and some promising research routes are also discussed. We highlight the centrality of its different biological activities, such as antioxidant, anti-inflammatory, antiproliferative, antiviral, and antinociceptive, among others. Recently, studies of the health effects of this plant suggest that novel nutraceuticals can be obtained from it and applied as a preventive or prophylaxis strategy before the start of conventional drug therapy, especially for patients who are not prone to conventional pharmacological approaches to diseases. The present work emphasizes the current pharmacological properties of Uncaria tomentosa, evidencing its therapeutic benefits and encouraging further research on this medicinal plant. Full article

Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex deposition in patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH). Methods: Immunohistochemistry of C4d, a widely used marker for complement deposition was employed on liver biopsies from 72 and 15 patients with CHB and AIH, respectively. Statistical analysis was performed to analyze its prevalence and its association with a range of clinical and histological parameters. Results: Among the 15 AIH biopsies examined, C4d deposition was observed in 11 cases (73.3%), the majority of which showed a periportal staining pattern (10/11). In CHB, 61 (84.7%) of 72 cases tested positive for C4d, which did not differ significantly with that of AIH. While the periportal pattern was predominantly observed in CHB cases, positive staining in central veins, sinusoids, and hepatic parenchyma were also documented. In particular, C4d deposition is significantly associated with elevated serum ALT and liver inflammation in CHB. Of note, in specimens with a patchy parenchymal C4d staining pattern, a spatially correlated HBsAg IHC signal was observed in adjacent sections from the same tissue. Conclusions: These data suggest an involvement of immune complex-mediated immunopathy in autoimmune hepatitis and HBV-induced hepatitis. The positive intrahepatic C4d signal was associated with heightened liver inflammation. The colocalization of the C4d signal on hepatocytes with HBsAg strongly suggests a causal relationship between viral activity and complement deposition. These observations align with our recent evidence implicating the contribution of capsid–antibody complexes in the pathogenesis of CHB. Full article

On 11 March 2020, the World Health Organisation (WHO) declared a global pandemic caused by the SARS-CoV-2 coronavirus that earlier in February 2020 the WHO had named COVID-19 (coronavirus disease 2019). There were neither drugs nor vaccines that were known to be effective against the virus, stimulating an urgent worldwide search for treatments. An evaluation of existing drugs by ‘repurposing’ was initiated followed by a transition to de novo drug discovery. Repurposing of an already approved drug may accelerate the introduction of that drug into clinical use by circumventing early, including preclinical studies otherwise essential for a de novo drug and reducing development costs. Early in the pandemic three drugs were identified as repurposing candidates for the treatment of COVID-19: (i) hydroxychloroquine, an anti-malarial also used to treat rheumatoid arthritis and lupus; (ii) ivermectin, an antiparasitic approved for both human and veterinary use; (iii) remdesivir, an anti-viral originally developed to treat hepatitis C. The scientific evidence, both for and against the efficacy of these three drugs as treatments for COVID-19, vied with public demand and politicization as unqualified opinions clashed with evidence-based medicine. To quote Hippocrates, “There are in fact two things, science and opinion; the former begets knowledge, the latter ignorance”. Full article

The Chikungunya virus (CHIKV) is a priority endemic pathogen identified by the World Health Organization and its infection induces an acute febrile illness in humans that is often associated with arthritis and musculoskeletal pain. Therefore, specific vaccines and treatments are urgently needed to prevent or treat Chikungunya disease. Here, we identify a series of CHIKV-specific neutralizing nanobodies (Nbs) from an alpaca which exhibit distinct binding modes compared to those previously reported. Two representative anti-CHIKV Nbs, N033-Fc and N053-Fc, demonstrated significant antiviral activity in Ifnar^−/− mice against lethal challenge. Further studies elucidated the functional mechanisms of N033-Fc and N053-Fc in blocking CHIKV infection at multiple stages of the viral life cycle. This study identifies multiple candidate Nbs that may be suitable for next-generation antibody therapies to combat CHIKV infection. Full article

Approaches capable of simultaneously treating cancer and protecting susceptible patients from lethal infections are highly desirable, although they prove challenging. Taking inspiration from the well-known anticancer platinum complexes, successive studies about the complexation of organic compounds with other late transition metals, such as silver, gold, palladium, rhodium, ruthenium, iridium, and osmium, have led to remarkable anticancer activities. Among the numerous chemical moieties studied, N-heterocyclic carbenes (NHCs) have revealed very attractive activities due to their favorable chemical properties. Specifically, gold–NHC complexes emerged as some of the most active complexes acting as antitumor agents. On the other hand, some recent studies have highlighted the involvement of these complexes in antiviral research as well. The well-known gold-based, orally available complex auranofin approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis has been suggested as a repositioned drug for both cancer and viral infections. In the era of the COVID-19 pandemic, the most interesting goal could be the discovery of gold–NHC complexes as dual antiviral and anticancer agents. In this review, the most recent studies regarding the anticancer and antiviral activities of gold(I)–NHC complexes will be analyzed and discussed, offering an interesting insight into the research in this field. Full article

Avian reovirus (ARV) is one of the main causes of viral arthritis, tenosynovitis, malabsorption syndrome (MAS), runting-stunting syndrome, and immunodepression. In recent years, due to the emergence of new ARV strains, outbreaks of the disease have brought significant economic losses to chicken flocks. To determine the prevalence of ARV in China from 2010 to 2024, a total of 409 tissue samples from different breeding farms were collected from chickens presenting clinical signs of lameness and swollen joints in various flocks located in 18 provinces. As performed on these tissue samples, the ARV-specific reverse transcription-polymerase chain reaction (RT-PCR) assay indicated 111 ARV-positive samples with a positive rate of 27.14%. After viral isolation from the necropsied chicken samples, 69 ARV strains were isolated, and specific sigma C (σC) genes were amplified and sequenced. The sequence analysis of σC genes showed that these 69 isolates were grouped into six clusters, including 14 ARV isolates from cluster I (20.29%), 12 ARV isolates from cluster II (17.39%), 3 ARV isolates from cluster III (4.35%), 8 ARV isolates from cluster IV (11.59%), 3 ARV isolates from cluster V (4.35%), and 29 ARV isolates from cluster VI (42.03%). Except for cluster V, each of the other five clusters could be divided into two subclusters. Homology analysis showed that ARV isolates in clusters II–VI had only 50.3 to 60.8% homology with the commercial S1133 vaccine strain which is derived from cluster I. The ARVs in subcluster Ia had high homology with the S1133 vaccine strain (93.5–98.0%), while the ARVs in subcluster Ib had a low homology with the S1133 strain (73.4–76.4%). Further, the cluster VI viruses, the main epidemic genotype in China, had only 50.3–55.7% homology with the S1133 strain. The results of the pathogenicity test showed that the representative strains of the six different clusters all caused swelling of the footpads in SPF chickens, and the incidence rate was not significantly different. The present study will be helpful in the understanding the prevalence of ARV strains in China and revealed the genetic differences between the ARV isolates and the commercial vaccine strain. Full article

Janus kinase inhibitors (JAKis) represent a relatively new class of immunomodulatory drugs with potent effects on various cytokine signalling pathways. They have revolutionized the treatment landscape for autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. However, their ability to modulate immune responses presents a dual-edged nature, influencing both protective immunity and pathological inflammation. This review explores the complex role of JAKis in infectious settings, highlighting both beneficial and detrimental effects. On the one hand, experimental models suggest that JAK inhibition can impair host defence mechanisms, increasing susceptibility to certain bacterial and viral infections. For example, tofacitinib-treated mice exhibited more severe joint erosions in Staphylococcus aureus (S. aureus) septic arthritis and showed impaired viral clearance in herpes simplex encephalitis. Additionally, clinical data confirm an increased risk of herpes zoster in patients receiving JAKis, underscoring the need for rigorous monitoring. On the other hand, JAK inhibition has demonstrated protective effects in certain infectious and hyperinflammatory conditions. In sepsis models, including cecal ligation and puncture (CLP) and S. aureus bacteraemia, tofacitinib improved survival by attenuating excessive inflammation. Furthermore, JAKis, particularly baricitinib, have shown substantial efficacy in mitigating cytokine storms during severe COVID-19 infections, leading to improved clinical outcomes and reduced mortality. These observations suggest that JAKis have a role in modulating hyperinflammatory responses in select infectious contexts. In conclusion, JAKis present a complex interplay between immunosuppression and immunomodulation. While they increase the risk of certain infections, they also show potential in managing hyperinflammatory conditions such as cytokine storms. The key challenge is determining which patients and situations benefit most from JAKis while minimizing risks, requiring a careful and personalized treatment approach. Full article

Rheumatoid arthritis (RA), an autoimmune disease with complex pathogenesis, is characterized by an immune imbalance reflected, e.g., in the disturbed cytokines’ profile. Various viruses and bacteria can cause the upregulation of pro-inflammatory cytokines influencing RA development. In particular, oral cavity dysbiosis, observed in multiple chronic diseases including periodontitis, may be linked to RA. The cytokine profile (IL-1β, IP-10, IL-29, GM-CSF, IFN-α2, IFN-β, TGF-β1, MPC-1, TNF-α, IFN-γ, IL-6, IL-10, IL-17A, IL-12p70, IL-2, and IL-4) of RA patients’ saliva was evaluated using flow cytometry and benchmarked with their levels in saliva of healthy controls and patients with other rheumatic diseases. The levels of IL-1β, IP-10, IL-2, and IL-4 were significantly elevated in RA patients’ saliva compared to other studied groups. To define the potential role of the most suspicious microbial agents (Epstein–Barr Virus (EBV), Cytomegalovirus, Parvovirus B19, Porphyromonas gingivalis, and Segatella copri) for RA pathogenesis, the amounts of their DNA in the saliva of patients with RA were assessed in all the groups mentioned above. The EBV and P. gingivalis DNA levels measured by qRT-PCR were significantly higher in RA patients’ saliva than in other groups, indicating either the important role of these agents in RA pathogenesis or the higher susceptibility of RA patients for those infectious factors. The comprehension of the association of specific cytokine profiles in RA and the occurrence of specific viral and/or bacterial infections can be a key to a better understanding of RA pathogenesis. These results illustrate the complexity of the immunological profile of RA, show the high diagnostic potential of saliva, and provide insight into how various infections can contribute to RA development. Full article

Viral infections leading to inflammation have been implicated in several common diseases, such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissociated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly, T1D, but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. The ACV treatment of sc-islets was not as effective in rescuing transcript perturbations of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial, and autophagy function. In addition, we compared transcriptomic signatures from HSV-1-infected sc-islets with sc-islets that were infected with the coxsackie B virus (CVB) that had been associated with T1D pathogenesis. Collectively, this study provides tissue-specific insights into the molecular effects of inflammation in AD and T1D. Full article

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3–4.1) vs. 2.0 (1.6–2.7); p = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (p < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data. Full article

Background: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy. Methods: We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren’s disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy. Results: Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA. Conclusions: In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions. Full article

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing a debilitating febrile illness with rheumatic disease symptoms of arthralgia and arthritis. Since its spread outside of Africa in 2005, it continues to cause outbreaks and disseminates into new territories. Intervention strategies are urgently required, including vaccination and antiviral approaches. To test efficacy, the use of small animal models is required. Two mouse strains, A129, with a deficiency in their type-I interferon (IFN) receptor, and C57BL/6 are widely used. A direct comparison of these strains alongside the wild-type parental strain of the A129 mice, 129Sv/Ev, was undertaken to assess clinical disease progression, viral loads in key tissues, histological changes and levels of sera biomarkers. Our results confirm the severe disease course in A129 mice which was not observed in the parental 129Sv/Ev strain. Of the two wild-type strains, viral loads were higher in 129Sv/Ev mice compared to C57BL/6 counterparts. Our results have established these models and parameters for the future testing of vaccines and antiviral approaches. Full article

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children. Full article

Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterised by lymphocytic infiltration of the exocrine glands, which leads to dryness of the eyes and mouth; systemic manifestations such as arthritis, vasculitis, and interstitial lung disease; and increased risks of lymphoma and cardiovascular diseases. SS predominantly affects women, with a strong genetic component linked to sex chromosomes. Genome-wide association studies (GWASs) have identified numerous single-nucleotide polymorphisms (SNPs) associated with primary SS (pSS), revealing insights into its pathogenesis. The adaptive and innate immune systems are crucial to SS’s development, with viral infections implicated as environmental triggers that exacerbate autoimmune responses in genetically susceptible individuals. Moreover, recent research has highlighted the role of vitamin D in modulating immune responses in pSS patients, suggesting its potential therapeutic implications. In this review, we focus on the recently identified SNPs in genes like OAS1, NUDT15, LINC00243, TNXB, and THBS1, which have been associated with increased risks of developing more severe symptoms and other diseases such as fatigue, lymphoma, neuromyelitis optica spectrum disorder (NMOSD), dry eye syndrome (DES), and adverse drug reactions. Future studies should focus on larger, multi-ethnic cohorts with standardised protocols to validate findings and identify new associations. Integrating genetic testing into clinical practise holds promise for improving SS management and treatment strategies, enabling personalised interventions based on comprehensive genetic profiles. By focusing on specific SNPs, vitamin D, and their implications, future research can lead to more effective and personalised approaches for managing pSS and its complications. Full article

Background: Viral infections, including coronavirus disease 2019 (COVID-19), in patients with autoimmune rheumatic diseases (AIRDs) tend to present more severe disease. This study aims to investigate the clinical characteristics and risk factors for severe infection in rheumatologic patients. Methods: We included patients with a diagnosis of AIRD and COVID-19 infection between January 2022 and July 2023. Patients with AIRDs infected with SARS-CoV-2 were matched with control patients of the general population according to age (±5 years) and sex in a 1:1 ratio. Confirmed infection was defined if a patient had a positive polymerase chain reaction (PCR) test. The severity was divided into mild, moderate, severe, and critical according to the guidelines of the United States National Institutes of Health (NIH). Results: A total of 140 individuals (37 males, 103 females; mean age 56.1 ± 11.3 years) with rheumatic disease diagnosed with COVID-19 infection were enrolled in the study. AIRDs included rheumatoid arthritis (RA) (n = 63, 45%), ankylosing spondylitis (AS) (n = 35, 25%), systemic lupus erythematosus (SLE) (n = 26, 8.6%), and systemic sclerosis (SSc) (n = 16, 11.4%). The AIRDs group had more SARS-CoV-2-related dyspnea (38.6%), arthralgia (45.7%), and depression (27.1%) than the control group (p = 0.004). The rate of lung infiltration on radiographic examination was higher in 58 (41.4%, p = 0.005) patients with rheumatic diseases than in those without them. Severe SARS-CoV-2 infection was more common in the AIRDs group than in the control group (22% vs. 12%; p = 0.043). Conclusions: Patients with AIRDs experienced more symptoms of arthralgia, depression, and dyspnea. There was a trend towards an increased severity of the disease in patients with AIRDs. Patients with arterial hypertension, diabetes, chronic lung, and kidney disease, treated with corticosteroids, had a longer duration, and high activity of autoimmune disease had an increased risk of severe COVID-19. Full article