Aflatoxin B1 (AFB1) can cause mitochondrial malfunction and immunosuppression in spleen. Mitochondrial damage can lead to oxidative stress and aggravate immune cell dysfunction. Phosphatase and ...tensin homolog (PTEN)-induced putative kinase1 (PINK1)/ E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy can scavenge damaged mitochondria and alleviate oxidative stress to maintain cellular homeostasis. However, the role of PINK1/Parkin-mediated mitophagy in AFB1-induced immunosuppression in spleen is unclear. In this study, sixty male mice were sensibilized orally with AFB1 at different concentrations 0, 0.5, 0.75, and 1 mg/kg body weight (BW) for 28 days, and AFB1 caused splenic structure injury and immunosuppression, also led to upregulation of PINK1/Parkin-mediated mitophagy in a dose-dependent manner. Subsequently, thirty male WT C57BL/6 N mice and thirty male Parkin knockout (Parkin-/-) C57BL/6 N mice were sensibilized orally with AFB1 at 0 or 1 mg/kg BW for 28 days, and Parkin-/- inhibited mitophagy and further aggravated AFB1-induced splenic structure injury, immunosuppression, mitochondrial damage and oxidative stress. Collectively, these results indicate that AFB1 exposure activates PINK1/Parkin-mediated mitophagy, which protects against immunosuppression in spleen.
•AFB1 activates PINK1/Parkin-mediated mitophagy in mice spleen.•Parkin-/- aggravates mitochondrial damage and oxidative stress in AFB1-treated spleen.•PINK1/Parkin-mediated mitophagy protects against immunosuppression in spleen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Fish gill was a target organ attacked by exogenous 4-OP.•C3a/C3aR axis and C5a/C5aR1 axis were involved in 4-OP-induced complement activation.•4-OP induced immunosuppression via the imbalances of ...Th1/Th2 and Treg/Th17 cells.•TLR7/IκBα/NF-κB pathway participated in inflammatory injury caused by 4-OP.•Complement activation mediated 4-OP-caused inflammatory damage via immunosuppression.
4-octylphenol (4-OP), a toxic estrogenic environmental pollutant, can threaten aquatic animal and human health. However, toxic effect of 4-OP on fish has not been reported. To investigate molecular mechanism of gill poisoning caused by 4-OP exposure, a carp 4-OP poisoning model was established, and then blood and gills were collected on day 60. The results demonstrated that gill was a target organ attacked by 4-OP, and exposure to 4-OP caused carp gill inflammatory injury. There were 1605 differentially expressed genes (DEGs, including 898 up-regulated DEGs and 707 down-regulated DEGs). KEGG and GO were used to further analyze obtained 1605 DEGs, indicating that complement activation, immune response, and inflammatory response participated in the mechanism of 4-OP-caused carp gill inflammatory injury. Our data at transcription level further revealed that 4-OP caused complement activation through triggering complement component 3a/complement component 3a receptor (C3a/C3aR) axis and complement component 5a/complement component 5a receptor 1 (C5a/C5aR1) axis, induced immunosuppression through the imbalances of T helper (Th) 1/Th2 cells and regulatory T (Treg)/Th17 cells, as well as caused inflammatory injury via toll like receptor 7/inhibitor kappa B alpha/nuclear factor-kappa B (TLR7/IκBα/NF-κB) pathway. Taken together, immunosuppression participated in complement activation-mediated inflammatory damage in carp gills after 4-OP treatment. The findings of this study will provide pioneering information and theoretical support for the mechanism of 4-OP poisoning, and will provide reference for the assessment of estrogenic environmental pollution risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Filariasis, an affliction caused by thread-like filarial worms, poses a formidable health challenge in India, with diverse regional endemicities. It manifests in two distinct forms: lymphatic and ...extralymphatic. The former induces agonising limb swelling, while the latter, often overlooked due to its atypical presentation, can affect various organs. Here we, present a noteworthy case involving a 25-year-old woman who succumbed to septic shock, displaying Multiple Organ Dysfunction Syndrome (MODS). The patient exhibited bicytopaenia, leukocytosis, and progressively deteriorating liver and kidney functions, culminating in Acute Respiratory Distress Syndrome (ARDS). Postmortem examinations, conducted with proper consent, revealed sheathed microfilaria in liver and bone marrow tissues. This rare multisystem involvement in filariasis, leading to a fulminant course, raises questions about potential immunosuppression triggered by disseminated filarial dissemination. The hypothesis centres on the notion that the systemic spread of filaria might underlie the severe and rapid deterioration observed in this unique case, shedding light on the intricate dynamics of this parasitic disease and its implications for immune function.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Patients considering total elbow arthroplasty (TEA) may be receiving immunosuppressive therapy; however, the relationship between immunosuppressive medications and postoperative complications is not ...well defined. Our purpose was to assess the relationship between preoperative immunosuppression and short-term complications following TEA.
The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2005 to 2020 to identify patients undergoing TEA. Procedures indicated for malignancy or infection were excluded. Patients were grouped according to preoperative chronic immunosuppressive status. Demographic and operative characteristics were compared between groups. The 30-day incidence of complications and reoperations were compared between groups. Multiple logistic regression models, inverse-weighted by propensity scores, were used to calculate odds ratio (OR) of experiencing any complication or return to the operating room based on immunosuppression status and other demographic characteristics.
A total of 769 patients undergoing TEA were included, of whom 142 (18.5%) received chronic immunosuppression. Distribution of age, sex, race, body mass index, diabetes, and American Society of Anesthesiologists classification differed significantly between groups. Most procedures were performed on an inpatient basis, and the median operative duration was 148 minutes. Most procedures were indicated for fracture in the nonimmunosuppressed group and rheumatoid arthritis in the immunosuppressed group. Overall complication rates were 7.0% for immunosuppressed patients and 10.2% for nonimmunosuppressed patients. The incidence of complications and reoperations did not significantly differ between groups. After controlling for confounding and adjusting for patient characteristics, immunosuppressed patients were 0.52 times less likely to experience a complication. Additionally, there was no association between immunosuppression status and odds of return to the operating room.
Similar rates of complications were observed following TEA, regardless of preoperative immunosuppression status. Chronic immunosuppression does not appear to increase the rates of postoperative complications for patients undergoing TEA.
Prognostic II.
Mesenchymal stem cells (MSCs)‐based therapeutic strategies have achieved remarkable efficacies. Oral tissue‐derived MSCs, with powerful self‐renewal and multilineage differentiation abilities, ...possess the features of abundant sources and easy accessibility and hold great potential in tissue regeneration and disease therapies. Oral MSCs mainly consist of periodontal ligament stem cells, gingival mesenchymal stem cells, dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and alveolar bone‐derived mesenchymal stem. Early immunoinflammatory response stage is the prerequisite phase of healing process. Besides the potent capacities of differentiation and regeneration, oral MSCs are capable of interacting with various immune cells and function as immunomodulatory regulators. Consequently, the immunomodulatory effects of oral MSCs during damage repair seem to be crucial for exploring novel immunomodulatory strategies to achieve disease recovery and tissue regeneration. Herein, we reviewed various oral MSCs with their immunomodulatory properties and the potential mechanism, as well as their effects on immunomodulation‐mediated disease therapies and tissue regeneration.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Immune profiling in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM) provides the framework for developing novel ...immunotherapeutic strategies. Here, we demonstrate decreased CD4
Th cells, increased Treg and G-type MDSC, and upregulation of immune checkpoints on effector/regulatory and CD138
cells in MM patients, compared MGUS/SMM patients or healthy individuals. Among the checkpoints profiled, LAG3 was most highly expressed on proliferating CD4
Th and CD8
Tc cells in MM patients BMMC and PBMC. Treatment with antibody targeting LAG3 significantly enhanced T cells proliferation and activities against MM. XBP1/CD138/CS1-specific CTL generated in vitro displayed anti-MM activity, which was further enhanced following anti-LAG3 treatment, within the antigen-specific memory T cells. Treg and G-type MDSC weakly express LAG3 and were minimally impacted by anti-LAG3. CD138
MM cells express GAL-3, a ligand for LAG3, and anti-GAL-3 treatment increased MM-specific responses, as observed for anti-LAG3. Finally, we demonstrate checkpoint inhibitor treatment evokes non-targeted checkpoints as a cause of resistance and propose combination therapeutic strategies to overcome this resistance. These studies identify and validate blockade of LAG3/GAL-3, alone or in combination with immune strategies including XBP1/CD138/CS1 multipeptide vaccination, to enhance anti-tumor responses and improve patient outcome in MM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
People living with HIV have accounted for 38–50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to ...those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3).
A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive.
We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30–43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117–291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100–200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance.
A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death.
None.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective To analyze the clinical characteristics of Legionnaires’ disease in immunosuppressive patients， and to explore the significance of blood metagenomic next-generation sequencing （mNGS） in the ...early diagnosis and treatment of Legionnaires’ disease in immunosuppressive patients. Methods A patient with angioimmunoblastic T-cell lymphoma who developed pulmonary infection after chemotherapy was reported. The diagnosis of Legionella pneumophila infection was confirmed by blood mNGS. Using “Legionella” “blood” “metagenomic next-generation sequencing” and “mNGS” as the keywords in both Chinese and English， relevant studies were searched from CNKI database， Chinese core journals and PubMed database. Clinical data of patients positive for Legionella pneumophila by blood mNGS were analyzed. Results The female patient， aged 50-year-old， was admitted to our hospital due to “the diagnosis of angioimmunoblastic T-cell lymphoma and continuing chemotherapy for more than 10 months”. After twice intravenous chemotherapy
The use of immunosuppressive medication following organ transplant has become increasingly prevalent as both numbers of transplants being performed and long-term survival increase. As a result, there ...may be an increase in patients requiring oral and maxillofacial surgery, and in particular orthognathic surgery, whilst taking immunosuppressive medication. This report explores some of the considerations for orthognathic surgery in this cohort, and strategies to mitigate risks associated with surgical management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Placebo Effects in the Immune System Hadamitzky, Martin; Sondermann, Wiebke; Benson, Sven ...
International review of neurobiology,
2018, Volume:
138
Journal Article
Peer reviewed
Even though knowledge and systematic application of placebo responses in the immune system are sparse, this topic is of particular importance since it may aim at drug-dose reduction while maintaining ...therapeutic efficacy of treatment in clinical settings. Placebo responses in the immune system are inducible by associated learning paradigms, such as behaviorally conditioned immunosuppression. One established learning paradigm in both rats and humans is conditioned taste avoidance (CTA), where a novel taste as conditioned stimulus (CS) is paired with the administration of the immunosuppressive drug cyclosporine A (CsA) as unconditioned stimulus. By representing the CS alone at a later time point, the conditioned response is reflected by avoidance behavior toward the taste (CTA). Simultaneously, diminished cytokine production and proliferative capacity of T cells are observed, closely mimicking the pharmacological effects of CsA. This chapter provides an overview on placebo responses in the immune system and delineates actual approaches, translational aspects, and limitations of learning paradigms in clinical settings.
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