Boosting NAD+ blunts TLR4-induced type I IFN in control and systemic lupus erythematosus monocytes

BACKGROUNDFasting and NAD⁺-boosting compounds, including NAD⁺ precursor nicotinamide riboside (NR), confer antiinflammatory effects. However, the underlying mechanisms and therapeutic potential are incompletely defined.METHODSWe explored the underlying biology in myeloid cells from healthy volunteers following in vivo placebo or NR administration and subsequently tested the findings in vitro in monocytes extracted from patients with systemic lupus erythematosus (SLE).RESULTSRNA-Seq of unstimulated and LPS-activated monocytes implicated NR in the regulation of autophagy and type I IFN signaling. In primary monocytes, NR blunted LPS-induced IFN-β production, and genetic or pharmacological disruption of autophagy phenocopied this effect. Given that NAD⁺ is a coenzyme in oxidoreductive reactions, metabolomics was performed and identified that NR increased the inosine level. Inosine supplementation similarly blunted autophagy and IFN-β release. Finally, because SLE exhibits type I IFN dysregulation, we assessed the NR effect on monocytes from patients with SLE and found that NR reduced autophagy and IFN-β release.CONCLUSIONWe conclude that NR, in an NAD⁺-dependent manner and in part via inosine signaling, mediated suppression of autophagy and attenuated type I IFN in myeloid cells, and we identified NR as a potential adjunct for SLE management.TRIAL REGISTRATIONClinicalTrials.gov registration numbers {"type":"clinical-trial","attrs":{"text":"NCT02812238","term_id":"NCT02812238"}}NCT02812238, {"type":"clinical-trial","attrs":{"text":"NCT00001846","term_id":"NCT00001846"}}NCT00001846, and {"type":"clinical-trial","attrs":{"text":"NCT00001372","term_id":"NCT00001372"}}NCT00001372.FUNDINGThis work was supported by the NHLBI and NIAMS Intramural Research divisions.     

Efficacy and safety of Sophora alopecuroides var. alopecuroides seed extract for opioid detoxification: A randomized,double‐blind,and placebo‐controlled clinical trial

The seeds of Sophora alopecuroides L. var. alopecuroides (S. alopecuroides) have alleviated morphine withdrawal in mice. Therefore, in this study, the alkaloid composition of S. alopecuroides extract was determined by gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS) analysis. Moreover, 50 abstinent opium addicts consumed three 400 mg extract capsules once daily and 50 other patients took placebo for 8 days. At the baseline and days 3 and 8, the clinical opiate withdrawal scale (COWS) was used to assess withdrawal symptoms. At the baseline and Day 8, the patients' blood levels of serum glutamate oxaloacetate transferase; serum glutamate pyruvate transferase; alkaline phosphatase; total, direct, and indirect bilirubins; creatinine and blood urea nitrogen; complete blood count; and prothrombine time were measured. The groups' parameter values were also compared. Sophocarpine, matrine, and sophoramine were the major alkaloids constituting, respectively, 32.85, 26.55, and 6.91% of the extract. The extract decreased the COWS score at Days 3 and 8 significantly compared with the placebo (p < .001). The extract did not significantly affect the blood parameters' values compared with the placebo (p > .05). There was no adverse drug effect. In conclusion, the extract reduces the acute opioid withdrawal symptoms and seems to have good safety and tolerability.     

Endothelial Trophic Support of Neuronal Production and Recruitment from the Adult Mammalian Subependyma

Vascular endothelial cells are among the first cells that ventricular zone neuroblasts encounter during early development. The ventricular zone cells promote angiogenesis by the invading vasculature, with the release of endothelial mitogens. Yet the feedback support of young neurons by endothelial cells (ECs) has not hitherto been explored. We therefore asked whether ECs might participate in neuronal recruitment, by providing neurotrophic support to newly generated neurons. We used the neurogenic subependymal zone (SZ) of the adult rat forebrain as a model system, because of its well-characterized and relatively homogeneous population of neuronal precursor cells. We found that explants of the adult rat SZ raised on ECs generated more neurons, which survived longer, than explants raised on astrocytes, fibroblasts, or laminin. This endothelial trophic effect was humoral, in that it was also noted in SZ explants raised in noncontiguous coculture with ECs grown on porous inserts. RT-PCR for neurotrophin family members revealed that cultures of both human brain- and umbilical cord-derived ECs produced brain-derived neurotrophic factor (BDNF) mRNA, but no detectable NGF, NT-3, or NT-4 mRNA. ELISA revealed that BDNF protein was secreted by ECs into the medium at >1 ng/ml. The neurotrophic effect of ECs could be replaced by added BDNF, and was blocked by addition of 5 microg/ml trkB-Fc to endothelial-SZ cocultures. Thus, endothelial cells can act as sources of secreted BDNF, through which the capillary microvasculature may act to support neuronal recruitment and survival in the CNS.     

Primary anterior shoulder dislocation and rotator cuff tears.

In a prospective controlled study 167 patients with 167 primary traumatic anterior shoulder dislocations underwent early ultrasonograpic evaluation for rotator cuff tears. We found 53 (31.7%) full-thickness cuff tears in this group. Compared with a group of 93 healthy volunteers, we found with statistical significance more cuff tears in the patients aged < 60 years. Women ruptured the cuff more often than men. If the patient is not able to elevate the affected arm more than 90 degrees in the scapular plane 2 weeks after the dislocation, there should be a high suspicion of rotator cuff tear (76.7%). For early detection of relevant rotator cuff lesions, we recommend shoulder ultrasonographic examination and measurement of active elevation after each traumatic shoulder dislocation in the above mentioned age group.     

Effects of Self-Lubricant Coating and Motion on Reduction of Friction and Wear of Mild Steel and Data Analysis from Machine Learning Approach

The applications of coated mild steels are gaining significant attention in versatile industrial areas because of their better mechanical properties, anticorrosive behavior, and reproducibility. The life period of this steel reduces significantly under relative motion in the presence of friction, which is associated with the loss of billion-dollar every year in industry. Productivity is hampered, and economic growth is declined. Several pieces of research have been conducted throughout the industries to seeking the processes of frictional reduction. This study is attributed to the tribological behavior of electroplated mild steel under various operating parameters. The efficiency of commercial lubricant and self-lubrication characteristics of coated layer plays a significant role in the reduction of friction. The reciprocating and simultaneous motion in relation to pin as well as disc are considered during experimentation. The lubricating effects in conjunction with motions are responsible for compensating the friction and wear at the desired level. During frictional tests, the sliding velocity and loads are changed differently. The changes in roughness after frictional tests are observed. The coated and rubbing surfaces are characterized using SEM (Scanning Electron Microscopy) analysis. The coating characteristics are analyzed by EDS (Energy Disperse Spectroscopy), FTIR (Fourier-transform Infrared Spectroscopy), and XRD (X-ray diffraction analysis) methods. The lubrication, reciprocating motion, and low velocity result in low friction and wear. The larger the imposed loads, the smaller the frictional force, and the larger the wear rate. The machine learning (ML) concept is incorporated in this study to identify the patterns of datasets spontaneously and generate a prediction model for forecasting the data, which are out of the experimental range. It can be desired that the outcomes of this research will contribute to the improvement in versatile engineering fields, such as automotive, robotics, and complex motion-based mechanisms where multidimensional motion cannot be ignored.     

Comparative study of three amniotic fluid markers in premature rupture of membranes: prolactin, beta subunit of human chorionic gonadotropin, and alpha-fetoprotein

OBJECTIVE: To evaluate whether prolactin, alpha-fetoprotein (AFP) or B-human chorionic gonadotropin (BHCG) is the most effective marker in vaginal fluid for diagnosing prelabor rupture of membranes (PROM). These proteins are present in amniotic and vaginal fluid and have been reported to be potent markers of PROM, but have not been used clinically nor compared to each other. STUDY DESIGN: A total of 100 pregnant women between 28 and 37 weeks of gestation were recruited for the study. Patients were divided into 2 groups. The first group consisted of 50 pregnant women diagnosed with ruptured membranes. The second group consisted of 50 normal pregnant women seen during routine antenatal clinic visit (control) group. All women underwent speculum examination aiming to sample prolactin, BHCG and AFP in the vaginal fluid. Ultrasonographic examination for gestational age and amniotic fluid index measurement was performed. The electrochemoluminescence (ECLIA) method was used for quantitative measurement of the three proteins (the total duration of the assay was 18 min). RESULTS: Vaginal fluid concentrations of the three markers were significantly higher in the PROM group than in the control group (p < 0.001). Receiver operator curve analysis indicated that AFP had 94% specificity, sensitivity, positive and negative predictive values, and efficiency. The other two markers have lower specificity, sensitivity, positive and negative predictive values, and efficiency: 70, 76, 71.7, 74.5 and 73% for prolactin and 72, 84, 75, 81.8 and 78% for BHCG, respectively. CONCLUSION: This work demonstrates that of the three markers investigated AFP has the highest diagnostic performance. Using the ECLIA method it can be an ideal marker for diagnosing PROM particularly in equivocal cases. The technique could be introduced into laboratory tests to meet clinical needs. Basel.     

Correction to: Behçet’s disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature

Clinical Rheumatology - The author wishes to correct the record and clarify that in the original version of this article in the Discussion section under “Prevalence over the country...