Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical management.Blood clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus development.Current evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic stroke.Various articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after stroke.FPR2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully explored.Recent literature suggests that FPR2 may play a role in the stimulation of scavenger receptor CD36.Scavenger receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix hemorrhage.FPR2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)gene.In this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

Reaction of antibodies to Campylobacter jejuni and cytolethal distending toxin B with tissues and food antigens

BACKGROUND The bacteria Campylobacter jejuni(C. jejuni) is commonly associated with GuillaneBarré syndrome(GBS) and irritable bowel syndrome(IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be crossreactive with some human tissues and food antigens, potentially leading to autoimmune responses.AIM To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin(Cdt) antibodies with tissue and food antigens to examine their role in autoimmunities.METHODS Using enzyme-linked immunosorbent assay(ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin(HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive controls.RESULTS At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, β-amyloid and presenilin.This immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, including neuronal antigens.The reaction of C. jejuni Cdt antibody with an additional 23 tissue antigens was insignificant. Regarding the reaction of C. jejuni Cdt antibody with different food antigens, 160 out of 180 foods showed insignificant reactions, while 20 foods showed reactions ranging from low to high.CONCLUSION Our findings indicate that C. jejuni and its Cdt may play a role in inflammation and autoimmunities beyond the gut.

Regulator of myeloid differentiation and function:The secret life of Ikaros

Ikaros (also known as Lyf-1) was initially described as a lymphoid-specific transcription factor.Although Ikaros has been shown to regulate hematopoietic stem cell renewal,as well as the development and function of cells from multiple hematopoietic lineages,including the myeloid lineage,Ikaros has primarily been studied in context of lymphoid development and malignancy.This review focuses on the role of Ikaros in myeloid cells.We address the importance of post-transcriptional regulation of Ikaros function;the emerging role of Ikaros in myeloid malignancy;Ikaros as a regulator of myeloid differentiation and function;and the selective expression of Ikaros isoform-x in cells with myeloid potential.We highlight the challenges of dissecting Ikaros function in lineage commitment decisions among lymphoidmyeloid progenitors that have emerged as a major myeloid differentiation pathway in recent studies,which leads to reconstruction of the traditional map of murine and human hematopoiesis.

Temperature variable and the efficiency of sperm mediated transfection of HPV16 DNA into cells

Aim:To pretreat sperm at various temperatures before exposure to human papillomavirus(HPV)16 DNA fragments and to assess the efficiency of HPV carrier sperm to transfect cumulus cells.Methods:Cumulus cells from follicular aspirates were obtained,pooled and divided into culture dishes containing Sybr Gold-stained HPV DNA carrying sperm that were either pretreated at 4℃,37℃or 40℃(n=5).The cells were incubated in 5%CO_(2) in air mixture at 37℃for 24 hours.The efficiency of sperm to take up fluorescent HPV DNA was determined at hour 0.After incubation,cumulus cell viability was assessed using the e0sin method and the percentages of fluorescent cumulus cells determined.Results:Over half of all the cumulus cells became fluorescent with the highest percentage in the 37℃group.Sperm pretreated at 4℃had the greatest amount of HPV DNA fragments.Total sperm motility was similar for the 3 pretreatment groups.There were no differences in cumulus viability among the groups.Conclusion:Sperm pretreated at 37℃transferred the greatest amount of fluorescent HPV DNA fragments to the cumulus cells.The HPV DNA was observed in the nuclear and cytoplasmic compartments.The data suggested the possibility of sperm as a vector for the transmission of HPV DNA to the cumulus cells surrounding ovulated oocytes,which might lead to early implantation failures.

Effect of aging on stem cells

Pluripotent stem cells have the remarkable self-renewal ability and are capable of differentiating into multiple diverse cells. There is increasing evidence that the aging process can have adverse effects on stem cells. As stem cells age, their renewal ability deteriorates and their ability to differentiate into the various cell types is altered. Accordingly, it is suggested aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various aging-associated disorders. Understanding the role of the aging process in deterioration of stem cell function is crucial, not only in understanding the pathophysiology of agingassociated disorders, but also in future development of novel effective stem cell-based therapies to treat agingassociated diseases. This review article first focuses on the basis of the various aging disease-related stem cell dysfunction. It then addresses the several concepts on the potential mechanism that causes aging-related stem cell dysfunction. It also briefly discusses the current potential therapies under development for aging-associated stem cell defects.

Effects of Benzo(a)pyrene on the Contractile Function of the Thoracic Aorta of Sprague-dawley Rats

Abstract Objective To evaluate the possible vascular effects of an environment carcinogen benzo（a）pyrene （BaP）. Methods The cytotoxicit of BaP and rat liver S9 （0.25 mg/mL）-activated BaP were examined by MTT assay. Thoracic aortic rings were dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60 mmol/L KCl or 10-6 mol/L phenylephrine （PE） in an ex-vivo perfusion system after BaP （100 tlmol/L） incubation for 6 h. [Ca^2＋]i was measured using Fluo-4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks （10 mg/kg, weekly, i.p.）. Results BaP （1-500 μm） did not significantly affect cell viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the contractile function of endothelium-intact or -denuded aortic rings. BaP did not affect ATP-induced （[Ca2＋]i） increases in human umbilical vein endothelial cells. In BaP-treated rats, heart rate and the number of circulating inflammatory cells were not affected. Body weight decreased while blood pressure increased significantly. The maximum aortic contractile responses to PE and KCI and the maximum aortic relaxation response to acetylcholine were significantly decreased by 25.0%, 34.2%, and 10.4%, respectively. Conclusion These results suggest, in accordance with its DNA-damaging properties, that metabolic activation is a prerequisite for BaP-induced cardiovascular toxicity.

Fluctuation of zonulin levels in blood vs stability of antibodies

To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients. METHODSThis study was conducted to assess the variability or stability of zonulin levels vs IgA and IgG antibodies against zonulin in blood samples from 18 controls at 0, 6, 24 and 30 h after blood draw. We also measured zonulin level as well as zonulin, occludin, vinculin, aquaporin 4 and glial fibrillary acidic protein antibodies in the sera of 30 patients with celiac disease and 30 controls using enzyme-linked immunosorbent assay methodology. RESULTSThe serum zonulin level in 6 out of 18 subjects was low or < 2.8 ng/mL and was very close to the detection limit of the assay. The other 12 subjects had zonulin levels of > 2.8 ng/mL and showed significant fluctuation from sample to sample. Comparatively, zonulin antibody measured in all samples was highly stable and reproducible from sample to sample. Celiac disease patients showed zonulin levels with a mean of 8.5 ng/mL compared to 3.7 ng/mL in controls (P < 0.0001). Elevation of zonulin level at 2SD above the mean was demonstrated in 37% of celiac disease patients, while antibodies against zonulin, occludin and other tight junction proteins was detected in up to 86% of patients with celiac disease. CONCLUSIONDue to its fluctuation, a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity. Measurement of IgG and IgA antibodies against zonulin, occludin, and other tight junction proteins is proposed for the evaluation of the loss of intestinal barrier integrity.

Filipin Levels as Potential Predictors of Alzheimer’s Disease Risk

To date, therapies to prevent or treat Alzheimer’s disease (AD) have largely focused on removing excess aggregation-prone amyloid peptide Aβ from the brain, an approach that has produced disappointing clinical outcomes. An alternative hypothesis proposes that Aβ production and aggregation is a symptom of a larger, systemic disease affecting the regulation of lipids, including cholesterol. In this scenario, lipid dysregulation would likely occur early in the disease process, making it an ideal target for predicting risk of mild cognitive impairment (MCI) to AD conversion. Here, we report that levels of filipin, a fluorescent polyene macrolide widely used as a diagnostic tool for diseases of lipid dysregulation, correlate with cellular damage caused by 27-hydroxycholesterol and with dementia status in human peripheral blood cells. These results provide strong preliminary data suggesting that filipin could be of use in the development of a quick and inexpensive method to measure the risk of AD conversion in patients with MCI, supplementing existing testing strategies that focus on the consequences of Aβ accumulation.

Telemonitoring in heart failure patients:Systematic review and metaanalysis of randomized controlled trials

BACKGROUND Home telemonitoring has been used as a modality to prevent readmission and improve outcomes for patients with heart failure.However,studies have produced conflicting outcomes over the years.AIM To determine the aggregate effect of telemonitoring on all-cause mortality,heart failure-related mortality,all-cause hospitalization,and heart failure-related hospitalization in heart failure patients.METHODS We conducted a systematic review and meta-analysis of 38 home telemonitoring randomized controlled trials involving 14993 patients.We also conducted a sensitivity analysis to examine the effect of telemonitoring duration,recent heart failure hospitalization,and age on telemonitoring outcomes.RESULTS Our study demonstrated that home telemonitoring in heart failure patients was associated with reduced all-cause[relative risk(RR)=0.83,95% confidence interval(CI):0.75-0.92,P=0.001]and cardiovascular mortality(RR=0.66,95%CI:0.54-0.81,P<0.001).Additionally,telemonitoring decreased the all-cause hospitalization(RR=0.87,95%CI:0.80-0.94,P=0.002)but did not decrease heart failurerelated hospitalization(RR=0.88,95%CI:0.77-1.01,P=0.066).However,prolonged home telemonitoring(12 mo or more)was associated with both decreased all-cause and heart failure hospitalization,unlike shorter duration(6 mo or less)telemonitoring.CONCLUSION Home telemonitoring using digital/broadband/satellite/wireless or blue-tooth transmission of physiological data reduces all-cause and cardiovascular mortality in heart failure patients.In addition,prolonged telemonitoring(≥12 mo)reduces all-cause and heart failure-related hospitalization.The implication for practice is that hospitals considering telemonitoring to reduce heart failure readmission rates may need to plan for prolonged telemonitoring to see the effect they are looking for.

Efficacy of minimally invasive video-assisted thyroidectomy for completion thyroidectomy

Objective:Minimally invasive video-assisted thyroidectomy(MIVAT)is among the most common alternatives to conventional open thyroidectomy.Previous reports have shown it to be safe and effective in patients without neck surgery history.However,this contraindication has been called into question in more recent small series.This study aims to evaluate the efficacy and safety of MIVAT in patients with prior neck surgery.Methods:We retrospectively reviewed the data of 178 patients who underwent completion thyroidectomy in the Department of Otolaryngology-Head and Neck Surgery at Loma Linda University Medical Center between July 2004 and July 2017.Patients were divided into MIVAT group and Conventional group based on method of surgery,and analysis with two sample tests of proportions was carried out as appropriate.Results:Patients in MIVAT group had significantly shorter operative time(74.1±26.4 min vs.99.0±49.3 min,p<0.001),less estimated blood loss(19.5±15.0 mL vs.39.0±65.9 mL,p¼0.002),smaller incision size(3.5±1.1 cm vs.6.2±2.2 cm,p<0.001),and a lighter thyroid weight(7.5±5.2 g vs.20.5±31.1 g,p<0.001).The average length of stay was a half day longer,and post-operative admission was higher(78.8%vs.51.7%,p¼0.005)in MIVAT group,while most was for routine 23-hour observation(63.6%vs.35.9%,p¼0.009).There were no differences in complications.Conclusion:MIVAT is feasible for re-operative patients with equivalent or superior outcomes to those of conventional thyroidectomy,and no significant difference in the incidences of common postoperative complications.

Duodenal Perforation Caused by Distal Migration of Biliary Stent

Background: Migration of endoscopically placed biliary stents is a known complication of endoscopic retrograde cholangiopancreatography, which has a reported incidence of 3% - 6%. Usually, distal migration is asymptomatic and is detected incidentally. Case Presentation: We present a rare case of duodenal perforation caused by distal migration of a biliary stent. A 50 years old gentleman initially presented with cholangitis. ERCP showed a dilated common bile duct with a 9 mm stone and a biliary stent was placed. The patient subsequently presented with biliary peritonitis due to the migration of the stent causing perforation of the anterior wall of the second part of the duodenum. Emergency laparotomy was performed to remove the stent and the perforation was repaired. The patient made an uneventful recovery. Discussion: A brief discussion on stent migration is also conducted. Whilst distal migration of stents is less common than its proximal counterpart, it is important to note that rare complications may arise and be addressed in a timely manner.

氢——一种内源性抗氧化剂(英文)

最近Ohsawa等报道,呼吸氢气能通过抗氧化作用,减少动物脑和肝缺血再灌注引起的细胞凋亡。实际上,人和动物消化道内许多正常细菌能产生氢气,这些氢气可被消化道吸收进入血液循环。考虑到小鼠部分器官内氢气水平已达到产生抗氧化作用的浓度,我们认为,氢是一种内源性抗氧化物质。

Bone marrow cells produce nerve growth factor and promote angiogenesis around transplanted islets

AIM:To clarify the mechanism by which bone marrow cells promote angiogenesis around transplanted islets.METHODS: Streptozotocin induced diabetic BALB/ c mice were transplanted syngeneically under the kidney capsule with the following: (1) 200 islets (islet group: n=12), (2) 1-5×106 bone marrow cells (bone marrow group: n=11), (3) 200 islets and 1-5×106 bone marrow cells (islet + bone marrow group: n= 13), or (4) no cells (sham group:n=5). All mice were evaluated for blood glucose, serum insulin, serum nervegrowth factor (NGF) and glucose tolerance (GTT) up to postoperative day (POD) 14. Histological assessment for insulin, von Willebrand factor (vWF) and NGF was performed at POD 3, 7 and 14.RESULTS: Blood glucose level was lowest and serum insulin was highest in the islet + bone marrow group. Serum NGF increased in islet, bone marrow, and islet + bone marrow groups after transplantation, and there was a significant difference (P=0.0496, ANOVA) between the bone marrow and sham groups. The number of vessels within the graft area was signif icantly increased in both the bone marrow and islet + bone marrow groups at POD 14 as compared to the islet alone group (21.2 ± 3.6 in bone marrow, P=0.01, vs islet group, 22.6 ± 1.9 in islet + bone marrow, P = 0.0003, vs islet group, 5.3 ± 1.6 in islet-alone transplants). NGF was more strongly expressed in bone marrow cells compared with islets. CONCLUSION: Bone marrow cells produce NGF and promote angiogenesis. Islet co-transplantation with bone marrow is associated with improvement of islet graft function.

足月新生儿窒息时阿片类药物的应用:对神经影像学检查结果及临床后果的影响

Perinatal asphyxia is a common cause of neurologic morbidity in neonates who are born at term. Asphyxiated neonates are frequently treated with analgesic medications, including opioids, for pain and discomfort associated with their care. On the basis of previous laboratory studies suggesting that opioids may have neuroprotective effects, we conducted a retrospective review of medical records of 52 neonates who were admitted to our neonatal intensive care unit between 1995 and 2002 and had undergone magnetic resonance imaging (MRI) of the brain. Our review revealed that 33% of neonates received morphine or fentanyl. The neonates who received opioids also had experienced hypoxic/ischemic insults of greater magnitude as suggested by higher plasma lactate levels and lower 5-min Apgar scores. It is interesting that the MRI studies of neonates who were treated with opioids during the first week of life demonstrated significantly less brain injury in all regions studied. More important, follow-up studies of a subgroup of opioid-treated neonates whose MRI scans were obtained in the second postnatal week had better long-term neurologic outcomes. Our results suggest that the use of opioids in the first week of life after perinatal asphyxia have no significant longterm detrimental effects and may increase the brain’ s resistance to hypoxic-ischemic insults.

Diagnosis of clinical and subclinical varicocele： how has it evolved？

In this review, we examine the evolution and application of various diagnostic modalities for varicoceles starting with venography, scintigraphy, and thermography and their role in the evaluation of a varicocele patient. Some of these methods have been supplanted by less invasive and more easily performed diagnostic modalities, especially ultrasound and Doppler examination of the scrotum. Advances in ultrasound and magnetic resonance imaging hold the potential to expand the role of imaging beyond that of visual confirmation and characterization of varicoceles. The ability to identify the early indicators of testicular dysfunction based on imaging findings may have implications for the management of varicoceles in the future.

Aminoflavone upregulates putative tumor suppressor miR-125b-2-3p to inhibit luminal A breast cancer stem cell-like properties

Metastatic breast cancer is incurable and often due to breast cancer stem cell(CSC)-mediated self-renewal.We previously determined that the aryl hydrocarbon receptor(AhR)agonist aminoflavone(AF)inhibits the expression of the CSC biomarkerα6-integrin(ITGA6)to disrupt the formation of luminal(hormone receptor-positive)mammospheres(3D breast cancer spheroids).In this study,we performed miRNA-sequencing analysis of luminal A MCF-7 mammospheres treated with AF to gain further insight into the mechanism of AF-mediated anti-cancer and anti-breast CSC activity.AF significantly induced the expression of>70 microRNAs(miRNAs)including miR125b-2–3p,a predicted stemness gene regulator.AF-mediated miR125b-2–3p induction was validated in MCF-7 mammospheres and cells.miR125b-2–3p levels were low in breast cancer tissues irrespective of subtype compared to normal breast tissues.While miR125b-2–3p levels were low in MCF-7 cells,they were much lower in AHR100 cells(MCF-7 cells made unresponsive to AhR agonists).The miR125b-2–3p mimic decreased,while the antagomiR125b-2–3p increased the expression of stemness genes ITGA6 and SOX2 in MCF-7 cells.In MCF-7 mammospheres,the miR125b-2–3p mimic decreased only ITGA6 expression although the antagomiR125b-2–3p increased ITGA6,SOX2 and MYC expression.AntagomiR125b-2–3p reversed AF-mediated suppression of ITGA6.The miR125b-2–3p mimic decreased proliferation,migration,and mammosphere formation while the antagomiR125b-2–3p increased proliferation and mammosphere formation in MCF-7 cells.The miR125b-2–3p mimic also inhibited proliferation,mammosphere formation,and migration in AHR100 cells.AF induced AhR-and miR125b2-3p-dependent anti-proliferation,anti-migration,and mammosphere disruption in MCF-7 cells.Our findings suggest that miR125b-2–3p is a tumor suppressor and AF upregulates miR125b-2–3p to disrupt mammospheres via mechanisms that rely at least partially on AhR in luminal A breast cancer cells.

Behavioral methods for the functional assessment of hair cells in zebrafish

Zebrafish an emerging animal model for studies comparability with humans, good accessibility to the hearing utilize this animal model, methodologies need to be used to on auditory system. This model presents high organ, and high throughput capacity. To better quantify the hearing function of the zebrafish. Zebrafish displays a series of innate and robust behavior related to its auditory function. Here, we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests, as follows： the startle response, the vestibular-ocular reflex, and rheotaxis. These tests are discussed in terms of their physiological characteristics, up-to-date technical development, and apparatus description. Test limitation and areas to improve are also introduced. Finally, we revealed the feasibility of these applications in zebrafish behavioral assessment and their potential in the high-throughput screening on hearing-related genes and drugs.

Animal models of necrotizing enterocolitis

background Necrotizing enterocolitis(NEC)is one of the leading causes of death in premature infants.To determine the factors present in the disease that lead to increased morbidity and mortality,manipulation of variables that are shown to have a positive response has been tested using various animal models.Testing and manipulation of these variables are unwarranted in humans due to regulatory health standards.Methods The purpose of this review is to provide an update to previous summaries that determine the significance of animal models in studying the mechanisms of NEC.A large variety of animal models including rats,mice,rabbits,piglets,nonhuman primates,and quails have been described in literature.We reviewed the reported animal models of NEC and examined the pros and cons of the various models as well as the scientific question addressed.results The animals used in these experiments were subject to gavage feeding,hypoxia,hypothermia,oxygen perfusion,and other methods to induce the disease state.Each of these models has been utilized to show the effects of NEC on the premature,undeveloped gut in animals to find a correlation to the disease state present in humans.We found specific advantages and disadvantages for each model.Conclusions Recent advances in our understanding of NEC and the ongoing therapeutic strategy developments underscore the importance of animal models for this disease.

The inauguration of the English issue of the Chinese Neurosurgical Journal

Editorial Almost a hundred years has passed since neurosurgery became an official surgical specialty of medicine.Forged from the field of general surgery, the founders of modern neurosurgery were able to progress the field despite having rudimentary methods of anesthesia, electrocautery, understanding of post-operative hematomas, and ways to monitor intracranial pressure.

Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy

Recent studies have demonstrated the potential of natural killer(NK)cells in immunotherapy to treat multiple types of cancer.NK cells are innate lymphoid cells that play essential roles in tumor surveillance and control that efficiently kill the tumor and do not require the major histocompatibility complex.The discovery of the NK’s potential as a promising therapeutic target for cancer is a relief to oncologists as they face the challenge of increased chemo-resistant cancers.NK cells show great potential against solid and hematologic tumors and have progressively shown promise as a therapeutic target for cancer immunotherapy.The effector role of these cells is reliant on the balance of inhibitory and activating signals.Understanding the role of various immune checkpoint molecules in the exhaustion and impairment of NK cells when their inhibitory receptors are excessively expressed is particularly important in cancer immunotherapy studies and clinical implementation.Emerging immune checkpoint receptors and molecules have been found to mediate NK cell dysfunction in the tumor microenvironment;this has brought up the need to explore further additional NK cell-related immune checkpoints that may be exploited to enhance the immune response to refractory cancers.Accordingly,this review will focus on the recent findings concerning the roles of immune checkpoint molecules and receptors in the regulation of NK cell function,as well as their potential application in tumor immunotherapy.