Sialic acids (Sias) in fish skin mucus play a crucial role in mediating interactions with the surrounding environment, serving as key components of the protective mucus that coats the fish. Sias contribute to the physical and chemical barriers that protect fish from pathogens and support mutualistic relationships with bacteria. In Atlantic salmon (Salmo salar), N-Glycolylneuraminic sialic acid (Neu5Gc) concentration in skin mucus and skin mucous cell (MC) parameters such as size, abundance, and volumetric density were monitored during the transition from freshwater to seawater across five sampling dates. A significant positive regression was observed between Neu5Gc concentration (free Neu5Gc and total Neu5Gc, encompassing both free and bound forms) and MC parameters in four of the five sampling points, suggesting a relationship between mucous barrier characteristics and Neu5Gc concentration in the mucus. Moreover, the transition to seawater resulted in a significant decrease in both MC parameters and Neu5Gc concentration (p < 0.05). Together, these findings support the interpretation that MCs represent a source of Neu5Gc in the skin mucus and that both Neu5Gc levels and MC characteristics appear to change during the transition to seawater.
Chronic lymphocytic leukemia is a B cell malignancy characterized by proliferation of B cells and is most prevalent in elderly populations that has poor prognosis in advanced stages. Bruton tyrosine kinase inhibitors such as ibrutinib and BCL-2 inhibitors such as venetoclax are considered one of the standard front-line treatments as shown by several clinical trials. However, several targeted and immunotherapies are emerging. Sonrotoclax is a BH3 mimetic BCL2i has been tested in combination with Zanubrutinib in phase I dose escalation/dose expansion study and resulted in a uMRD4 rates of 78% at a 320mg dose in the peripheral blood. No disease progression at a median follow-up of 10 months resulted with no atrial fibrillation and grade 3 infections at 8% of patients. Two clinical studies describe the construction of CAR T cell therapies for the treatment of CLL. CAR T cell therapies in two clinical studies describe constructions which are definite options, and combinations of BCL-2 and BTK inhibitors have been evaluated especially for double refractory disease. One study provided a protocol to recapitulate the TME of CLL to further precision medicine approaches for the disease with the aim of understanding resistance targeted therapies. Another agent, VIP152, is a selective CDK9 inhibitor with pre-clinical in vitro and in vivo efficacy that phosphorylates RNA POLII by positive transcription elongation factor complex (P-TEFb). It is a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, producing dysregulated transcripts in CLL.
Misfolding of the cellular prion protein (PRPC) is associated with fatal neurodegenerative prion diseases for which no treatments are currently available. Although the immune system is generally non-responsive (tolerant) to self-proteins such as PRPC, evidence of anti-prion antibodies suggests escape from self-tolerance in some individuals and supports the potential for the human immune system to be leveraged against prion disease. Human leukocyte antigen (HLA) plays a central role in rejecting endogenous non-self proteins (e.g. cancer neoantigens) by activating CD8+ cytolytic T cells via the Class I system (HLA-I) and CD4+ helper T cells via the Class II (HLA-II) system. Here we investigated the predicted binding affinity of 334 HLA molecules with all possible linear 9-mer (for HLA-I) and 15-, 18- and 22-mer (for HLA-II) PRPC peptides to identify peptide-HLA (pHLA) complexes with strong predicted binding (IC50 < 50 nM). We found that 12.4% of all prion peptides tested showed strong binding affinity to HLA molecules and that 20.2% of HLA alleles were able to bind strongly with PRPC peptides. These findings suggest that carriers of certain HLA alleles that are capable of binding strongly to PRPC peptides may have enhanced protection against prion disease, through reduction in the overall amount of PRPC available for conversion to the misfolded, infectious scrapie isoform (PRPSc) of PRPC and, potentially, by destroying it. These findings have implications for other disorders including common neurodegenerative diseases characterized by protein misfolding (e.g. α-synuclein, huntingtin, amyloid, tau, etc.).
The present mini-review explore the therapeutic potential of nanomedicine in advancing immunotherapy for primary and metastatic brain tumors, addressing existing challenges and paving the way for transformative precision therapy. Primary brain tumors including glioblastoma and metastases from other cancers like breast, lung etc., experiences limitation in treatment outcomes due to the tumor heterogeneity, immunosuppressive tumor microenvironment (TME), the blood-brain-barrier (BBB), and therapy resistance. Although, immunotherapies have shown promising benefits, however are hindered by immune escape, organ toxicities, and variable patient responses. Major unresolved challenges include insufficient therapeutic penetration across the BBB, the inability to reprogram the immunosuppressive TME, limited strategies to counteract dynamic tumor antigen escape, and systemic toxicities associated with conventional therapies. To address these challenges, multifunctional nanomedicines offer promising solutions through precise and controlled delivery, immunosuppressive TME modulation, and/or recalibration of immune system. Advanced nanomaterials including lipid/polymer-based system, dendrimers, and quantum dots, can co-deliver immunomodulators and chemotherapeutic/radiosensitizers, enhances BBB permeability, and activate favorable immune responses. Nanomedicines with multimodality such as localized hyperthermia (e.g. photothermal ablation), and immunogenic cell death stimulate immunological memory and improve therapeutic benefits. Furthermore, innovation in gene therapy (e.g. CRISPR-Cas9) and personalized cancer vaccines enhance targeted anti-tumor immune responses. Despite these groundbreaking advancements challenges persist, including nanoparticles-biological interactions (protein corona effects), stability, scalability, and regulatory hurdles. However, emerging trends such as 3D organoids, organ-on-a-chip system, patient-derived xenografts, and integration of AI/ML platforms, offer physiologically relevant platforms to optimize nanotherapy with better response predictions. Moreover, surface functionalization such as solid-lipid nanoparticles targeting programmed death–ligand 1 (PD-L1)-epidermal growth factor receptor (PD-L1/EGFR), have demonstrated success in augmenting the abscopal effect of radiotherapy. Radiotherapy enhances tumor antigen cross-presentation by inducing immunogenic cell death (ICD), leading to the release of tumor-associated antigens (TAAs). This process is accompanied by the release of damage-associated molecular patterns (DAMPs), such as calreticulin, HMGB1, and ATP. These signals recruit and activate dendritic cells (DCs), which engulf tumor antigens and process them via the major histocompatibility complex (MHC) class I, facilitating the activation of cytotoxic T lymphocytes (CTLs) against the tumor (S. Zhu et al., 2022). Nanoparticles (NPs) can improve antigen delivery by encapsulating tumor antigens and immune-modulatory agents, ensuring prolonged antigen presentation. Furthermore, radio-enhancing NPs, such as gold or hafnium oxide nanoparticles, intensify the effects of radiation by increasing DNA damage and reactive oxygen species (ROS) production, which strengthens the ICD response and improves antigen release (He et al., 2025). In order to further enhance immune activation, some NPs are also designed to modulate the tumor microenvironment by promoting pro-inflammatory signaling.
Chimeric antigen receptor-T (CAR-T) cell therapy in the treatment of solid tumors remains limited, though it has demonstrated remarkable success for hematological malignancies. One of the major restrictions is immune escape from the attack mediated by primary targeted CAR-T cells, driven by the heterogeneous cell components of solid tumors, including heterogeneous expression of tumor antigens. Here, we reviewed the specified challenges and corresponding strategies which are being developed, including the use of multi-targeted CAR-T cells and the activation of endogenous immune responses.
Purpose: The purpose of this study was to examine the potential of a novel method for quantifying salivary immunoglobulin A (sIgA) using a point of care device. Method: This novel method included the use of a non-invasive oral fluid collector, lateral flow strips, and a cube reader device to collect and evaluate sIgA. Volunteers were recruited to collect saliva for analysis over three separate evaluations. These evaluations examined the precision, accuracy, and robustness of the method. Result: Results indicated that this novel method could provide a reasonably reliable and fast option to monitor sIgA levels at an accessible price point. Conclusion: This method could be a useful tool to improve individuals' ability to self-monitor important health biomarkers and gain insight into the status of their oral immunity with minimal effort and at a low cost compared to current standard methods.
The coronavirus disease (COVID-19) pandemic has posed unique challenges for individuals with autoimmune and autoinflammatory rheumatic diseases (AARDs), raising critical concerns about susceptibility, disease severity, treatment outcomes, and vaccine response. This mini-review draws on data from a national Greek cohort and global studies. It summarizes current evidence on disease course and risk stratification in AARD patients with COVID-19.Most patients experienced mild disease; however, those with advanced age, interstitial lung disease (ILD), and treatment with rituximab, mycophenolate mofetil, or corticosteroids demonstrated increased risk for hospitalization and mortality. In contrast, biologics targeting pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) were not associated with worse outcomes and, in some analyses, correlated with reduced hospitalization rates. Notably, long-term sequelae, particularly persistent fatigue, emerged as a common burden, underscoring the overlap between post-viral symptoms and underlying autoimmune dysfunction. The serologic response to SARS-CoV-2 infection and vaccination was attenuated in some AARD subgroups, especially in patients receiving B-cell depleting therapies, emphasizing the need for tailored immunization and preventive strategies. Additionally, anosmia was inversely associated with hospitalization and may represent a biomarker of milder disease and more effective early immune responses. This review highlights key predictors of adverse outcomes and discusses implications for immunosuppression management, vaccination timing, and long-term care. As the pandemic evolves, identifying high-risk AARD patients and implementing precision prevention and treatment strategies remain vital priorities.
Here we offer a perspective on recent findings of persistent SARS-CoV-2 antigens in Long COVID1 through the lens of immunogenetic risk and protection, namely in the context of the fundamental role of Human Leukocyte Antigen (HLA) in eliminating viral infections. Specifically, we attribute the persistence of viral antigens to the lack or weak protection conferred by HLA against SARS-CoV-2 in individuals carrying HLA alleles with low binding affinities to the virus. We suggest that determining the HLA Class I and II makeup of Long COVID patients will provide valuable new information in elucidating the cause for antigen persistence underlying the development of Long COVID and pave the way for successful interventions.
Human leukocyte antigen (HLA) is widely recognized to influence individual Type 1 diabetes (T1D) risk. Here we utilized an immunogenetic epidemiological approach to evaluate the influence of HLA on T1D at the population level. Specifically, we evaluated the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of T1D in 14 Continental Western European countries to identify a population-level HLA profile for T1D. The results of these analyses generally corroborated prior findings regarding the influence of HLA on T1D risk and protection and revealed several novel HLA-T1D associations. The findings, discussed within the context of the role of HLA in pathogen elimination and autoimmunity, point to a contributory role of exposure to pathogens in the absence of protective HLA in underlying the autoimmune destruction of pancreatic beta cells in T1D.
The COVID-19 pandemic continues to impart devastating effects on human health, healthcare systems, and the economy. Vaccination, monoclonal antibodies, and antiviral therapies prevent and limit early infection. Unfortunately, few strategies exist to mitigate the disease burden in the vast number of individuals who seek medical attention with established infection and severe disease. While we have a limited understanding of the mechanistic basis by which SARS-CoV-2 causes critical illness, increasing evidence suggests that host-pathogen interactions shape immune responses that drive the pathogenesis of COVID-19. Therefore, it is imperative to understand the roles of the viral proteins and how they shape the course of infection. One interesting protein is the envelope (E) protein of SARS-CoV-2; this tiny structural protein has been implicated in many phases of the viral life cycle. Importantly, the E protein facilitates viral packaging and replication, and its deletion reduces viral pathogenicity. The E protein also possesses ion channel functions, interacts with host proteins, and has the potential to have various structural topologies. This review aims to establish an updated understanding by highlighting recent developments in the investigation of the SARS-CoV-2 E protein, particularly in comparison to the envelope protein of SARS-CoV. thorough knowledge of this protein will enable targeted studies in hopes of tailored efficacious treatments.
The concern about anesthesia-induced developmental neurotoxicity (AIDN) in infants and young children arises from animal studies indicating potential long-term neurobehavioral impairments following early-in-life anesthesia exposure. While initial clinical studies provided ambiguous results, recent prospective assessments in children indicate associations between early-in-life anesthesia exposure and later behavioral alterations. Ethical constraints and confounding factors in clinical studies pose challenges in establishing a direct causal link and in investigating its mechanisms. This commentary on a recent study in non-human primates (NHPs) focuses on exploring the role of neuroinflammation and alterations in brain functional connectivity in the behavioral impairments following early-in-life anesthesia exposure. In juvenile NHPs, chronic astrogliosis in the amygdala correlates with alterations in functional connectivity between this area with other regions of the brain and with the behavioral impairments, suggesting a potential mechanism for AIDN. Despite acknowledging the study's limitations, these findings emphasize the need for further research with larger cohorts to confirm these associations and to establish a causal link between the neuroinflammation and the behavioral alterations associated with early-in-life anesthesia exposure.
This paper examines the impact of insecurity on the management of the Ebola virus disease epidemic in the Democratic Republic of the Congo provinces of North Kivu and Ituri. In these provinces, insecurity has been one of the biggest obstacles in the response to the Ebola outbreak. When the epidemic began, these provinces were already insecure—creating unfavorable circumstances for implementing epidemic response activities. While the ninth epidemic in the Equateur province was brought under control in record time, the same was not true for the tenth epidemic in North Kivu and Ituri. Since the epidemic began, teams were organized to address all aspects of the response. These response teams conducted extensive fieldwork, including epidemiological surveillance, risk communication and community involvement, infection prevention and control, vaccination, dignified and safe burials, care at transit centers and Ebola treatment centers, and medical and psychosocial care for the recovered. They faced confrontational reactions from the communities, which jeopardized their security. The insecure state of the provinces led to the destruction and damage of infrastructure, including healthcare facilities, which affected the ability of rescue teams to access people needing care as well as the resources they needed to care for the ill. Worse yet, the insecurity took other forms, including threatening and kidnapping members of the response teams, lodging protests against the response activities in towns or health zones, committing violence against teams responsible for safe and dignified burials, instigating altercations between community members and members of the response team, and encouraging general resistance by the population. This level of insecurity interrupted or even halted response activities in some areas—sometimes for more than two weeks, decreasing the efficiency of the response teams, particularly in monitoring contacts due to the inability to access certain communities. Additionally, certain acts of protest, such as community members handling bodies as a demonstration of their opposition to safe and dignified burials, likely intensified disease spread. However, the involvement of community leaders, at least, made dialogue and negotiation possible between the response teams and community members, as such efforts led to communities contributing to the security of personnel involved in the fight against the Ebola epidemic in North Kivu and Ituri provinces.
We reviewed the involvement of civil society organizations as well as other community level organizations and structures in the response to the Ebola Virus Disease (EVD) outbreak in the Democratic Republic of Congo. A total of 800 randomly selected adults were surveyed using a uniform set of structured questionnaires. An in-depth interview guide was employed to collect information from community members and religious leaders, while focus group discussions were held with community members. The results revealed some involvement of the different organizations in the communities in the response to the EVD outbreak. However, several challenges were encountered, namely security issues, poor awareness, and non-compliance to safety measures. The findings underscore that despite considerable experience over a long period with outbreaks in the DRC, people still need to be educated about the disease.
Treatment centers (TCs) are the only locations designed to care for people with Ebola virus disease (EVD) symptoms. These people and their families are held at a TC as soon as they arrive at an Ebola treatment center (ETC); however, some people escape from TCs. This paper explored alternative care platforms for symptomatic people in the fight against the EVD outbreak in the Democratic Republic of Congo. Eight hundred randomly selected adults aged 18 years and above were surveyed with a uniform set of structured questionnaires. In-depth interviews were conducted with 20 community/opinion leaders, while focus group discussions were held with community members who were not involved in the questionnaire study. Our findings demonstrated that people who were suspected of having EVD preferred to be treated discreetly and at home, and were more willing to be tested at home than at a TC. People were afraid of being stigmatized if the TC exposed their admittance to the general public. This article proposes an alternative to the TCs. We suggest a temporary containment facility within the community, such as a room in the suspected person’s home. However, this requires negotiation between the response team and community members, with the latter having a significant responsibility in caring for their symptomatic relatives. The place or room for domestic temporary isolation should be chosen discreetly and placed far from the view of others. Community members will, thus, bear more responsibility for what happens while the patient is in isolation. The temporary containment area will assist in decentralizing the treatment of those with EVD symptoms. Its implementation will contribute to greater accountability of community members in the fight against EVD.
We investigated the involvement of community members in response to the Ebola Virus Disease (EVD) epidemic in the North Kivu and Ituri provinces of the Democratic Republic of Congo. This cross-sectional study, conducted using mixed methods of data collection, included a uniformly structured questionnaire survey, which was administered to 800 randomly selected adults (aged ≥ 18 years). Further, we used qualitative tools of inquiry—focus group discussions (FGD) and in-depth interviews (IDI)—to guide the context of the information collected in the survey. Community leaders, religious leaders, and Ebola survivors were interviewed using the IDI guide, while young men (≤ 30 years), young women (≤30 years), adult community males (<30 years), and adult community females (<30 years) were in separate FGD sessions. The results revealed that the urban area was the most affected by the epidemic (79.2%) compared to 20.8% in rural areas. The χ2 calculated was 18.183 (P<0.001). Community members exhibited varying degrees of involvement in response to the EVD epidemic in the two provinces. Community members were mostly engaged in information dissemination. However, they believe they could have contributed more if they had been fully engaged. These findings were derived from the qualitative data. The study contributes to evidence on how community involvement could help response to public health events globally, hence this study provides valuable insights for future public health interventions and response.
While treating a disease, patients or their relatives make decisions to pursue different therapeutic options, and various stages are involved in searching for a cure. This paper explored the pattern of health-seeking in the Democratic Republic of Congo (DRC) during the 10th Ebola virus disease (EVD) outbreak. Eight hundred randomly selected adults were surveyed using a questionnaire. Qualitative data were also collected through in-depth interviews with 17 community leaders and 20 focus group discussions with community members. The results showed that modern healthcare facilities are not usually considered the first option for treatment. The therapeutic journey generally begins with the patients, who treat themselves based on the information they know about the disease and the resources they have at their disposal. However, if the disease is not cured through self-medication, then patients or their relatives will visit a pharmacy. Patients request medication they know to be effective in treating the disease, and relatives can also assist in obtaining medication in the case of immobile patients. Pharmacies commonly sell the medication to patients or their relatives without a medical prescription.
Although an outbreak of the Ebola virus disease affects an entire population, women are more susceptible to the virus than men. Throughout the outbreaks of the Ebola virus disease in Central and West Africa, women have been impacted more significantly. Generally, over half of those who become ill are women. The situation is the same in terms of mortality. Further, the outcomes of the epidemic negatively affect women socially, as many become the heads of households following the loss of their spouses, which burdens them with new responsibilities. Women's access to health services is also lowered, as the epidemic usually leads to fewer healthcare workers, impacting gynecological assistance. Consequently, women are more exposed to health problems, particularly during pregnancy. Several factors contribute to the greater exposure of women to the Ebola virus disease during an epidemic. First, female healthcare workers are at the frontline of the fight against the virus. Second, women's duties in the domestic context increase their exposure to contamination, as they look after children and care for sick household members. Finally, women are responsible for several community duties such as public tasks and rituals. In the case of rituals, women undertake tasks such as undressing, washing, and dressing the deceased. Likewise, they engage in agricultural work and grocery shopping locally, as well as at cross-border markets. They also manage domestic chores such as fetching water in public places. Additionally, women have less access to information on the disease and its prevention and are thus more vulnerable. However, women's vulnerability is less visible, since information on the epidemic and response is not gender specific. This is true for the number of suspected cases, confirmed cases, vaccinated people, alerts, contacts, contacts followed up, and screened travelers. It is therefore crucial to highlight the importance of gender in the response to the Ebola virus disease epidemic, as women are the primary victims.
Perceptions and rumors about vaccinations can contribute to vaccine hesitancy. This study aimed to examine perceptions and rumors about the Ebola vaccine during the 10th Ebola Virus Disease outbreak in the Ituri and North Kivu provinces of the Democratic Republic of Congo. Eight hundred randomly selected respondents were surveyed with a uniform structured questionnaire. Further, we collected qualitative data through focus group discussions and using in-depth interview guides. Results revealed several misperceptions and rumors about the vaccine, which led to some level of vaccine hesitancy and refusal among the people. The acceptance rate of the vaccine was 67.3% (below the 80% threshold needed to create herd immunity in the population). More of the urban population (31.3%) than the rural population (10.4%) accepted the vaccine. Refusals were largely due to fear that the vaccine could activate other diseases in the body and could even kill. Some feared that it was a conspiracy of the government to reduce the population in the study area through forced fertility control and death, among other such concerns. In conclusion, these rumors increased mistrust, which challenged the efforts of the government and its partners to safeguard the health of the people.
The medical response to monkeypox(mpox) is a key demonstration of how COVID-19 remodeled the global response to viruses in the medical field. As a result of the 2019 pandemic, the 2022 mpox outbreak was met with mass production of vaccines, widely available PCR testing, and increased public health and research efforts. Easy access to vaccines such as the ACAM2000 and the JYNNEOS vaccines bolstered prevention while antivirals alleviated symptoms and shortened viral duration in at-risk patients. Various methods of detection have been developed for mpox over a short period with PCR currently being used in an attempt to isolate specific strains of the virus. In this brief review, we discuss its classical presentation, and detection and treatment strategies adapted to mitigate this public health risk.
