The antibody response to Epstein–Barr virions is altered in multiple sclerosis

Infection with Epstein–Barr virus (EBV) is associated with multiple sclerosis (MS), and patients with MS have an increased antibody response to some EBV antigens. The major antigens of EBV are only partly defined. Our hypothesis is that the antibody response to EBV is altered in MS. With ELISA, we found that antibodies to EB virions were increased in both serum and CSF of MS patients. Western blots demonstrated that there are multiple different antigens recognized. The antibody response was generally higher in MS to all EBV antigens, with particularly significant increases for certain antigens. We conclude that the antibody response to EBV in MS is generally increased with altered specificity.     

Clinical application of Aconitum carmichaelii Debx. (Fu Zi in Chinese) by traditional Chinese medicine physicians--A cross-sectional questionnaire survey in Beijing

ObjectiveTo investigate clinical application of aconite root (Aconitum carmichaelii Debx.; hereinafter “aconite”) by traditional Chinese medicine (TCM) physicians in TCM hospitals in Beijing and explore the specific use of aconite and the effect of different doses on decoction time.MethodsThis was a cross-sectional study using two-stage sampling. Questionnaires were administered among TCM physicians from TCM hospitals in Beijing between September 2020 and August 2021. The questionnaire mainly included general demographics, clinical backgrounds of TCM physicians, and clinical application of aconite. The data analyses were performed using SPSS 20.0.ResultsA total of 387 questionnaires were collected, of which 385 were valid. Of the 385 participating TCM physicians, 331 (85.97%) used aconite in clinical practice. The top three medical diagnoses treated with aconite were heart failure, diarrhea without cause, and chronic gastritis. The TCM pattern treated most frequently with a high dose of aconite was spleen-kidney yang deficiency, and the TCM pattern treated most frequently with a low dose was spleen yang deficiency, while spleen-kidney yang deficiency was treated most frequently with a common dose of aconite. The top three common formulas were Sini decoction, Mahuang Xixin Fuzi decoction, and Zhenwu decoction. Hei Shun Pian was the most common herbal pieces of aconite. The highest frequency of the maximum dose of aconite was 15 g, that of the minimum dose was 3 g, and that of the common dose was 10 g. There was a certain correlation between decoction time and the dose of aconite. Most TCM physicians advised their patients to take medicine twice a day.ConclusionIn this study, we refined and quantified the use of aconite and enriched the exploration of the clinical application of aconite besides its provisions in the Pharmacopoeia of the People's Republic of China.     

Postmarketing safety evaluation: depside salt injection made from Danshen (Radix Salviae Miltiorrhizae)

ObjectiveTo systematically examine the postmarketing safety of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), identify the potential risk factors, and ensure its clinical safety.MethodsWe examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae). Data from I-IV clinical drug trials, hospital information systems (HIS), and spontaneous reporting systems (SRS) were also analyzed.ResultsThe effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached more than 80%. The median lethal dose (LD50) calculated by the Bliss method was 1.49 g/kg, with 95% confidence intervals of 1.29–1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions (ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen (Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.ConclusionThis study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.     

CTRP4 acts as an anti-inflammatory factor in macrophages and protects against endotoxic shock

Despite the availability of antibiotics, current therapies to treat sepsis are still ineffective and many clinical trials aimed at neutralizing specific inflammatory cytokines have failed, suggesting the urgent need for new treatments. Using two models of LPS-induced endotoxemia and cecal ligation and puncture (CLP)–induced sepsis, we investigated the effects of C1q/TNF-related protein 4(CTRP4) on septic lethality and sepsis-induced inflammation. The effects of CTRP4 on survival, inflammation, organ damage, and bacterial clearance were assessed. Here, we found that CTRP4 decreased the mortalities of mice and alleviated pathological lung injury in mice model. In vivo depletion and adoptive transfer studies showed CTRP4-expressing macrophages as the key cell type inhibiting LPS-induced septic shock. The mechanism associated with the CTRP4 deficiency involved promoting of TLR4 internalization and activation of downstream pathways that resulted in a lethal, prolonged proinflammatory cytokine storm. Treatment of macrophages with exogenous CTRP4 abrogated proinflammatory cytokine production. Our results showed CTRP4 regulates inflammatory response and could be a promising strategy to treat septic shock.     

Changes in Heart Rate Variability in Patients with Spleen-Qi Deficiency Syndrome

Many functional diseases are related to dysautonomia, and heart rate variability has been used to assess dysautonomia. However, heart rate variability has not been studied in Spleen-Qi deficiency syndrome (SQDS). Healthy volunteers (n = 37) and patients with SQDS (n = 67), recruited from the Clinic of the State University of Ecatepec Valley were included in the study. Outcome measures were average heart rate, standard deviation of the normal-to-normal heartbeat intervals, low frequency (LF), high frequency (HF) power, and the LF/HF ratio. Also, intestinal peristalsis, gastrointestinal symptoms (GSs), fatigue, and level of attention were measured. Standard deviation of the normal-to-normal heartbeat intervals (17 ± 2.3%) and HF (14 ± 3.1%) were lower in SQDS patients (17 ± 1.3%) than in healthy volunteers. SQDS patients had higher heart rate, LF power, LF/HF ratio, and fatigue scores (9.6 ± 1.12%, 16 ± 2.1%, 22 ± 3.8%, and 21 ± 4.1%). The fatigue correlated positively with the LF/HF ratio and negatively with HF power. The SQDS group had lower concentration performance (16.2 ± 1.9%) in the d2 test. The intestinal peristalsis showed a reduction (15 ± 1.3%) as compared with control. GS score and peristalsis correlated negatively with HF. Our results suggest that the pathology of SDQS could be associated with a low vagal tone which causes a decrease in peristalsis, increased fatigue, reduced attention, and appearance of GSs.     

The protective effect of melatonin on smoke‐induced vascular injury in rats and humans: a randomized controlled trial

Smoking is one of the most harmful lifestyles in the world. Very few studies have investigated the effects of melatonin in smoke‐induced vascular injury. This study was designed to investigate whether melatonin could protect rats and humans from smoke‐induced vascular injury. 32 male rats and a double‐blind randomized controlled trial (RCT) containing 63 participants formed the subjects of this study. In rats, 10 mg/kg of melatonin was intraperitoneally injected. Blood samples and abdominal artery were harvested two weeks later. Melatonin decreased the expression of platelet endothelial cell adhesion molecule‐1 (CD31), intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and endothelin‐1 (ET‐1) compared with the smoke exposed group (P < 0.05), whereas endothelial nitric oxide synthase (eNOS), nuclear erythroid 2‐related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO‐1), catalytic glutamate cysteine ligase (GCLC) and heme oxygenase‐1 (HO‐1) recovered markedly (P < 0.05). In humans, 3 mg/day of melatonin was taken orally by the participants. Blood samples were drawn at baseline and after two weeks of treatment. Compared with the oral placebo group, melatonin decreased the concentration of fibrinogen (Fbg) (P = 0.04) and free fatty acids (FFA) (P = 0.04) in smokers, along with the decreased expression of ICAM‐1, VCAM‐1 and ET‐1 (P = 0.004, P = 0.001, P < 0.0001, respectively). In contrast, Nrf2 and HO‐1 expression were markedly increased (P = 0.0001, P = 0.0049, respectively) after smokers took melatonin orally. In summary, our present data suggest that melatonin could ameliorate smoke‐induced vascular injury.     

Evaluation of the protective efficacy of four newly identified surface proteins of Erysipelothrix rhusiopathiae

Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and human erysipeloid. Bacterial surface proteins are promising vaccine candidates. We recently identified 3 E. rhusiopathiae surface proteins (GAPDH, HP0728, and HP1472) and characterized their roles as virulence factors. However, their efficacy as protective antigens is still unknown. The N-terminal region of a previously identified surface protein, CbpB (CbpB-N), is speculated to be a protective antigen, but this needs to be verified. The aim of this study was to evaluate the protective efficacy of GAPDH, HP0728, HP1472, and CbpB-N. Immunization with recombinant GAPDH provided complete protection in a mouse model, recombinant CbpB-N provided partial protection, while recombinant HP0728 and HP1472 provided no protection. Recombinant GAPDH also provided good protection in a pig model. GAPDH antiserum exhibited significant blood bactericidal activity against E. rhusiopathiae. In conclusion, GAPDH and CbpB-N were found to be protective antigens of E. rhusiopathiae, and GAPDH is a promising vaccine candidate.     

TRAIL receptor deficiency sensitizes mice to dextran sodium sulphate‐induced colitis and colitis‐associated carcinogenesis

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor (TRAIL-R) play important roles in immune regulation and cancer cell death. Although TRAIL has been shown to induce chemokine release in various tumour cells, the function of TRAIL-R in the development of colitis and colitis-associated carcinogenesis has not been explored. In this study, we found that TRAIL-R-deficient mice exhibited a higher incidence of colitis and colitis-associated cancer than that of wild-type (WT) mice, and TRAIL-R expression was down-regulated in WT mice that were fed dextran sulphate sodium. Chemokines, including CCL2 and CXCL1, were highly expressed in the serum and inflammatory colon tissues of TRAIL-R^−/− mice compared with WT mice, and TRAIL-R^−/− mice showed a marked infiltration of immune cells during colitis. Hyperactivation of Janus kinase and nuclear factor-κB in colon epithelial cells was also observed, which correlated with the severity of colonic inflammation in TRAIL-R^−/− mice. These data suggest that TRAIL-R plays a protective role in chemical-induced colon injury and negatively regulates mucosal immune responses.