S100A8/A9: An emerging player in sepsis and sepsis-induced organ injury.

Sepsis, the foremost contributor to mortality in intensive care unit patients, arises from an uncontrolled systemic response to invading infections, resulting in extensive harm across multiple organs and systems. Recently, S100A8/A9 has emerged as a promising biomarker for sepsis and sepsis-induced organ injury, and targeting S100A8/A9 appeared to ameliorate inflammation-induced tissue damage and improve adverse outcomes. S100A8/A9, a calcium-binding heterodimer mainly found in neutrophils and monocytes, serves as a causative molecule with pro-inflammatory and immunosuppressive properties, which are vital in the pathogenesis of sepsis. Therefore, improving our comprehension of how S100A8/A9 acts as a pathological player in the development of sepsis is imperative for advancing research on sepsis. Our review is the first-to the best of our knowledge-to discuss the biology of S100A8/A9 and its release mechanisms, summarize recent advances concerning the vital roles of S100A8/A9 in sepsis and the consequential organ damage, and underscore its potential as a promising diagnostic biomarker and therapeutic target for sepsis.

Utility of adjuvant radioactive iodine therapy after reoperation in papillary thyroid carcinoma with cervical lymph node recurrence.

PURPOSE: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. MATERIALS AND METHODS: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RESULTS: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. CONCLUSIONS: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.

Meisoindigo inhibits cellular proliferation via down-regulation of the PI3K/Akt pathway and induces cellular apoptosis in glioblastoma U87 cells.

OBJECTIVE: The current study was to explore whether meisoindigo was effective in suppressing proliferation and inducing apoptosis of human glioblastoma multiforme U87 cells and to explore its possible mechanisms. METHOD: Morphological changes were observed by light microscopy. Cell counting kit-8 (CCK-8) assay was performed to detect cellular proliferation. Apoptosis was monitored by flow cytometry. Akt, phospho-Akt, PI3K, p65, phospho-p65 and apoptosis-related proteins caspase-3 and caspase-9 were examined by Western blotting assays. Immunofluorescence was used to evaluate level of P65 expression in cells. RESULT: Meisoindigo inhibited the proliferation of U87 cells, and the inhibitory effect increased in a dose dependent manner. Moreover, meisoindigo exposure triggered an increase in the level of caspase-3 and caspase-9, supporting its role in the activation of apoptosis. Furthermore, meisoindigo reduced the expression of PI3K, Akt, phospho-Akt, NF-κB, p65 and phospho-p65 in U87 cells, and displacement of p65 from the nucleus to the cytoplasm. CONCLUSION: Meisoindigo inhibits proliferation and induces apoptosis of U87 cells, probably through down-regulating the PI3K/Akt pathway and reducing nuclear translocation of NF-κB p65.

The immune response of T cells and therapeutic targets related to regulating the levels of T helper cells after ischaemic stroke.

Through considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

Chimeric Antigen Receptor T-Cell Therapy in Glioblastoma: Current and Future.

Glioblastoma (GBM) is a highly aggressive glioma with an extremely poor prognosis after conventional treatment. Recent advances in immunotherapy offer hope for these patients with incurable GBM. Our present review aimed to provide an overview of immunotherapy for GBM, especially chimeric antigen receptor T-cell (CAR T) therapy. CAR T-cell immunotherapy, which involves the engineering of T cells to kill tumors by targeting cell surface-specific antigens, has been successful in eliminating B-cell leukemia by targeting CD19. IL-13Rα2, EGFRvIII, and HER2-targeted CAR T cells have shown significant clinical efficacy and safety in phase 1 or 2 clinical trials conducted in patients with GBM; these findings support the need for further studies to examine if this therapy can ultimately benefit this patient group. However, local physical barriers, high tumor heterogeneity, and antigen escape make the use of CAR T therapy, as a treatment for GBM, challenging. The potential directions for improving the efficacy of CAR T in GBM are to combine the existing traditional therapies and the construction of multi-target CAR T cells.

The Involvement and Therapy Target of Immune Cells After Ischemic Stroke.

After ischemic stroke, the integrity of the blood-brain barrier is compromised. Peripheral immune cells, including neutrophils, T cells, B cells, dendritic cells, and macrophages, infiltrate into the ischemic brain tissue and play an important role in regulating the progression of ischemic brain injury. In this review, we will discuss the role of different immune cells after stroke in the secondary inflammatory reaction and focus on the phenotypes and functions of macrophages in ischemic stroke, as well as briefly introduce the anti-ischemic stroke therapy targeting macrophages.

Microbiota-gut-brain axis and the central nervous system.

The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway.

Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF-κB signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF-κB p65, and IκBα were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF-α, IL-1ß, and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, IκB-α degradation, and nuclear translocation of NF-κB. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF-κB mediated inflammatory signaling pathway.