Erector Spinae Plane Block for Pain Management in Hepatocellular Carcinoma Patients Undergoing Laparoscopic Left Hemihepatectomy: A Retrospective Propensity Score-matched Study.

Objective: The objective of this investigation was to ascertain the effectiveness of an ultrasound-guided erector spinae plane block (ESPB) administered to patients diagnosed with hepatocellular carcinoma who were subjected to laparoscopic left hemihepatectomy.

Methods: A retrospective analysis was conducted on 172 patients, comparing 2 groups: one comprising 90 individuals who were administered intravenous patient-controlled analgesia (PCA) simultaneously with ESPB, and a second group of 82 patients who received PCA monotherapy. To equilibrate covariates across the groups, propensity score matching was executed, yielding 25 matched pairs as a result.

A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination.

Background: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines.

Objective: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions.

Methods: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health.

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e.

A novel murine in vivo model for acute hereditary angioedema attacks.

Hereditary Angioedema (HAE) is a rare genetic disease generally caused by deficiency or mutations in the C1-inhibitor gene, SERPING1, a member of the Serpin family. HAE results in acute attacks of edema, vasodilation, GI pain and hypotension. C1INH is a key inhibitor of enzymes controlling complement activation, fibrinolysis and the contact system.

Early antibody responses associated with survival in COVID19 patients.

Neutralizing antibodies to the SARS CoV-2 spike proteins have been issued Emergency Use Authorizations and are a likely mechanism of vaccines to prevent COVID-19. However, benefit of treatment with monoclonal antibodies has only been observed in clinical trials in outpatients with mild to moderate COVID-19 but not in patients who are hospitalized and/or have advanced disease. To address this observation, we evaluated the timing of anti SARS-CoV-2 antibody production in hospitalized patients with the use of a highly sensitive multiplexed bead-based immunoassay allowing for early detection of antibodies to SARS-CoV-2.

Serum Alkaline Phosphatase Predicts Poor Disease-Free Survival in Patients Receiving Radical Gastrectomy.

BACKGROUND Serum alkaline phosphatase (ALP) has been proved to be a negative prognostic factor for several malignancies, but its clinical significance in gastric cancer (GC) patients has not been sufficiently studied. In the present retrospective study, we investigated the effect of serum ALP on disease-free survival (DFS) after radical gastrectomy. MATERIAL AND METHODS We included 491 GC patients receiving radical gastrectomy at the Chinese People's Liberation Army 309th Hospital.

Therapeutic potential of the heme oxygenase-1 inducer hemin against Ebola virus infection.

Promising drugs to treat Ebola virus (EBOV) infection are currently being developed, but so far none has shown efficacy in clinical trials. Drugs that can stimulate host innate defense responses may retard the progression of EBOV disease. We report here the dramatic effect of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of EBOV replication.

Defective iron homeostasis in human immunodeficiency virus type-1 latency.

Highly active antiretroviral therapy has significantly improved the life of HIV-1-infected individuals, yet complete eradication of HIV-1 reservoirs (i.e., latently infected cells) remains a major challenge.

Oversulfated chondroitin sulfate binds to chemokines and inhibits stromal cell-derived factor-1 mediated signaling in activated T cells.

Oversulfated chondroitin sulfate (OSCS), a member of the glycosaminoglycan (GAG) family, was a contaminant in heparin that was linked to the 2008 heparin adverse events in the US. Because of its highly negative charge, OSCS can interact with many components of the contact and immune systems. We have previously demonstrated that OSCS inhibited the complement classical pathway by binding C1 inhibitor and potentiating its interaction with C1s.

Polyreactive antibodies plus complement enhance the phagocytosis of cells made apoptotic by UV-light or HIV.

Polyreactive antibodies are a major component of the natural antibody repertoire and are capable of binding a variety of structurally unrelated antigens. Many of the properties attributed to natural antibodies, in fact, are turning out to be due to polyreactive antibodies. In humans, each day, billions of cells undergo apoptosis.

Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages.

We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy.

Heme oxygenase-1-mediated host cell response inhibits the susceptibility of prostate cancer cells to retroviral infection and retards their proliferation.

Xenotropic murine leukemia virus-related virus (XMRV) resembles endogenous murine leukemia virus and was used in this study as a model for a new retrovirus infecting human cells. We demonstrate that induction of an HO-1-mediated host cell response inhibited the susceptibility of LNCaP prostate cancer cells to XMRV infection and efficiently retarded the growth of these prostate cancer cells. Our studies delineate a role of HO-1 in the host defense against retroviral infections and may provide novel therapeutic strategies for the treatment of HO-1-sensitive prostate cancer.

Oversulfated chondroitin sulfate inhibits the complement classical pathway by potentiating C1 inhibitor.

Oversulfated chondroitin sulfate (OSCS) has become the subject of multidisciplinary investigation as a non-traditional contaminant in the heparin therapeutic preparations that were linked to severe adverse events. In this study, it was found that OSCS inhibited complement fixation on bacteria and bacterial lysis mediated by the complement classical pathway. The inhibition of complement by OSCS is not due to interference with antibody/antigen interaction or due to consumption of C3 associated with FXII-dependent contact system activation.

Clinical observation of gastric bypass in treatment of type 2 diabetes.

Background: Roux-en-Y gastric bypass (GBP) is the main surgical procedure used in type 2 diabetes. The objective of this study was to evaluate the different types of GBP in treatment of type 2 diabetes.

Methods: Patients with type 2 diabetes were randomly divided into two groups: those who underwent gastrojejunal loop anastomosis bypass and those who underwent gastrojejunal Roux-en-Y bypass.

Complement C1 esterase inhibitor levels linked to infections and contaminated heparin-associated adverse events.

Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics.

Differential regulation and recovery of intracellular Ca2+ in cerebral and small mesenteric arterial smooth muscle cells of simulated microgravity rat.

Background: The differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca(2+) determined by the alterations in the functions of plasma membrane Ca(L) channels and ryanodine-sensitive Ca(2+) releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively.

Methodology/principal Findings: Sprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity.

High glucose alters apoptosis and proliferation in HEK293 cells by inhibition of cloned BK Ca channel.

It has been reported that diabetic vascular dysfunction is associated with impaired function of large conductance Ca(2+) -activated K(+) (BK(Ca) ) channels. However, it is unclear whether impaired BK(Ca) channel directly participates in regulating diabetic vascular remodeling by altering cell growth in response to hyperglycemia. In the present study, we investigated the specific role of BK(Ca) channel in controlling apoptosis and proliferation under high glucose concentration (25 mM).

Lipopolysaccharide up-regulates IL-6R alpha expression in cultured leptomeningeal cells via activation of ERK1/2 pathway.

To clarify the response of leptomeningeal cells to immune stimulation, the effect of lipopolysaccharide (LPS) on expression of IL-6 receptors in the cultured leptomeningeal cells was investigated. The results showed that the expression of IL-6R alpha was invisible in the purified leptomeningeal cells while it was seen in the cells when they were co-cultured with astrocytes. On the other hand, GP130 was moderately expressed in both conditions.

The broad antibacterial activity of the natural antibody repertoire is due to polyreactive antibodies.

Polyreactive antibodies bind to a variety of structurally unrelated antigens. The function of these antibodies, however, has remained an enigma, and because of their low binding affinity their biological relevance has been questioned. Using a panel of monoclonal polyreactive antibodies, we showed that these antibodies can bind to both Gram-negative and Gram-positive bacteria and acting through the classical complement pathway can inhibit bacterial growth by lysis, generate anaphylatoxin C5a, enhance phagocytosis, and neutralize the functional activity of endotoxin.

Properties and function of polyreactive antibodies and polyreactive antigen-binding B cells.

The advent of hybridoma technology has made it possible to study in-depth individual antibody molecules. These studies have revealed a number of surprises that have and are continuing to change our view of the immune system. None of these was more surprising than the demonstration that many antibody molecules are polyreactive - that is they can bind to a variety of different and structurally unrelated self- and non-self-foreign antigens.

Urokinase-type plasminogen activator stimulation of monocyte matrix metalloproteinase-1 production is mediated by plasmin-dependent signaling through annexin A2 and inhibited by inactive plasmin.

Chronic inflammatory diseases are associated with connective tissue turnover that involves a series of proteases, which include the plasminogen activation system and the family of matrix metalloproteinases (MMPs). Urokinase-type plasminogen activator (uPA) and plasmin, in addition to their role in fibrinolysis and activation of pro-MMPs, have been shown to transduce intracellular signals through specific receptors. The potential for uPA and plasmin to also contribute to connective tissue turnover by directly regulating MMP production was examined in human monocytes.

Sensitization of multiple myeloma and B lymphoma lines to dexamethasone and gamma-radiation-induced apoptosis by CD40 activation.

We examined the effects of CD40 activation with dexamethasone (Dex) or 60Co-gamma-irradiation on the growth of malignant B cells in vitro, using the human multiple myeloma (MM) cell line, XG2, and the B lymphoma Daudi cell line as models. Both lines are resistant to Dex and irradiation; 10(-7)M Dex or 10 Gy of gamma-irradiation induced only minimal growth arrest and apoptosis of the cells. Treatment of the cells with the agonistic anti-CD40 monoclonal antibody 5C11 partially inhibited the proliferation of the Daudi cells; XG2 underwent apoptosis.

gp130-linked signal transduction promotes the differentiation and maturation of dendritic cells.

In order to explore the role of gp130-linked signal transduction in the differentiation and maturation of dendritic cells (DC), the mAb, B-S12, an agonist of gp130, was used for the activation of gp130 on DC. The effects of cytokines and of anti-gp130 mAb on the proliferation of DC, and their expression of IL-12 and CD80 (B7-1) by DC were evaluated. DC differentiating from peripheral blood mononuclear cells did not express the IL-6 receptor alpha chain, but expressed gp130.