Miracle-dz/UniFAR-FTUs huggingface dataset:
Hydrogen sulfide‐releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation

Endogenously generated hydrogen sulfide (H2S) may have multiple functions in brain. It has been shown that H2S attenuates the expression of pro‐inflammatory cytokines by lipopolysaccharide (LPS)‐activated microglia. Here we demonstrate a neuroprotective effect of NaSH and three H2S‐releasing compounds, ADT‐OH, S‐diclofenac, and S‐aspirin. When activated by LPS and γ‐interferon, human microglia and THP‐1 cells release materials that are toxic to human neuroblastoma SH‐SY5Y cells. These phenomena also occur with γ‐interferon‐stimulated human astroglia and U118 cells. When these cell types are pretreated with aspirin, diclofenac, NASH, or ADT‐OH, the supernatants are significantly less toxic. When they are treated with the NSAID‐H2S hybrid molecules S‐diclofenac and S‐aspirin, which are here referred to as S‐NSAIDs, there is a significant enhancement of the protection. The effect is concentration and incubation time dependent. Such pretreatment also reduces the release of the proinflammatory mediators TNFα, IL‐6, and nitric oxide. The H2S‐releasing compounds are without effect when applied directly to SH‐SY5Y cells. These data suggest that hybrid H2S releasing compounds have significant antiinflammatory properties and may be candidates for treating neurodegenerative disorders that have a prominent neuroinflammatory component such as Alzheimer disease and Parkinson disease. © 2009 Wiley‐Liss, Inc.
The possible mechanism of preterm birth associated with periodontopathic Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE Previous studies have shown that Porphyromonas gingivalis is found in the amniotic fluid and placentae of pregnant women with some obstetric diseases. However, the biological effects of P. gingivalis on intrauterine tissues remain unclear. The aim of this study was to investigate the presence of P. gingivalis in chorionic tissues from hospitalized high-risk pregnant women, and the effects of P. gingivalis lipopolysaccharide on the production of proinflammatory molecules in human chorion-derived cells. MATERIAL AND METHODS Twenty-three subjects were selected from Japanese hospitalized high-risk pregnant women. The presence of P. gingivalis in chorionic tissues was analyzed by PCR. Cultured chorion-derived cells or Toll-like receptor-2 (TLR-2) gene-silenced chorion-derived cells were stimulated with P. gingivalis lipopolysaccharide. Real-time PCR was performed to evaluate TLR-2 and Toll-like receptor-4 (TLR-4) mRNA expression in the cells. Levels of interleukin-6 and interleukin-8 in culture supernatants of the chorion-derived cells were measured by ELISA. RESULTS P. gingivalis DNA was detected in chorionic tissues from two women with threatened preterm labor, two with multiple pregnancy and two with placenta previa. Stimulation of chorion-derived cells with P. gingivalis lipopolysaccharide significantly increased TLR-2 mRNA expression, whereas TLR-4 mRNA expression was not changed. P. gingivalis lipopolysaccharide induced interleukin-6 and interleukin-8 production in chorion-derived cells, but the P. gingivalis lipopolysaccharide-induced interleukin-6 and interleukin-8 production was reduced in TLR-2 gene-silenced chorion-derived cells. CONCLUSION Our results suggest that P. gingivalis can be detected in chorionic tissues of hospitalized high-risk pregnant women, and that P. gingivalis lipopolysaccharide induces interleukin-6 and interleukin-8 production via TLR-2 in chorion-derived cells.
Blueberry supplementation attenuates microglial activation in hippocampal intraocular grafts to aged hosts

Transplantation of central nervous tissue has been proposed as a therapeutic intervention for age‐related neurodegenerative diseases and stroke. However, survival of embryonic neuronal cells is hampered by detrimental factors in the aged host brain such as circulating inflammatory cytokines and oxidative stress. We have previously found that supplementation with 2% blueberry in the diet increases graft growth and neuronal survival in intraocular hippocampal grafts to aged hosts. In the present study we explored possible biochemical mechanisms for this increased survival, and we here report decreased microglial activation and astrogliosis in intraocular hippocampal grafts to middle‐aged hosts fed a 2% blueberry diet. Markers for astrocytes and for activated microglial cells were both decreased long‐term after grafting to blueberry‐treated hosts compared with age‐matched rats on a control diet. Similar findings were obtained in the host brain, with a reduction in OX‐6 immunoreactive microglial cells in the hippocampus of those recipients treated with blueberry. In addition, immunoreactivity for the pro‐inflammatory cytokine IL‐6 was found to be significantly attenuated in intraocular grafts by the 2% blueberry diet. These studies demonstrate direct effects of blueberry upon microglial activation both during isolated conditions and in the aged host brain and suggest that this nutraceutical can attenuate age‐induced inflammation. © 2009 Wiley‐Liss, Inc.
Genetic ablation of steroid receptor coactivator‐3 promotes PPAR‐β‐mediated alternative activation of microglia in experimental autoimmune encephalomyelitis

Steroid receptor coactivator‐3 (SRC‐3) has been demonstrated to regulate lipid metabolism by inhibiting adipocyte differentiation. In this study, the potential role of SRC‐3 in experimental autoimmune encephalomyelitis (EAE), which characterized by inflammatory demyelination in central nervous system (CNS), was examined by analyzing disease progression in SRC‐3‐deficient (SRC‐3−/−) mice. We found that SRC‐3 deficiency significantly attenuated the disease severity of EAE along with decreased inflammatory infiltration and demyelination. However, these effects are not caused by inhibition of peripheral T cell response, but by upregulated expression of peroxisome proliferator‐activated receptor (PPAR)‐β in CNS, which induced an alternative activation state of microglia in SRC‐3−/− mice. These alternatively activated microglia inhibited CNS inflammation through inhibition of proinflammatory cytokines and chemokines, such as TNF‐α, IFN‐γ, CCL2, CCL3, CCL5, and CXCL10, as well as upregulation of anti‐inflammatory cytokine IL‐10 and opsonins, such as C1qa and C1qb. Moreover, microglia alternative activation promoted myelin regeneration through increased accumulation of oligodendrocyte precursors in white matter and elevated expression of myelin genes in the spinal cords of SRC‐3−/− mice. Our results build up a link between lipid metabolic regulation and immune functions, and the modulation of the expression of SRC‐3 or PPAR‐β may hopefully has therapeutic modality in MS and possibly other neurodegenerative diseases. © 2010 Wiley‐Liss, Inc.
Effects of supplementation with omega-3 fatty acids during pregnancy on asthma or wheeze of children: a systematic review and meta-analysis

Abstract Objective: To evaluate the effects of omega-3 fatty acids during pregnancy on the incidence of wheeze and asthma of children. Methods: A search was conducted in PubMed, Embase and CENTRAL until September 2017. Randomized controlled trials (RCTs) assessing the effects of omega-3 fatty acids during pregnancy on wheeze/asthma of children were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Outcomes of relative risks were pooled. Subgroup analyses were conducted. Results: Seven RCTs involving 2047 children were included. The pooled data revealed the supplementation during pregnancy reduced the incidence of wheeze/asthma (risk ratio (RR) 0.81; 95% CI 0.66–0.99; p . 04), but the incidence of childhood asthma was not significantly reduced (RR 0.89; 95% CI 0.67–1.17; p .40). Subgroup analyses indicated that the risk of childhood wheeze/asthma was significantly decreased (1) in studies located in Europe (RR 0.67 95% CI 0.51– 0.88), (2) in children whose first-degree relatives were diagnosed with allergic disease (RR 0.65 95% CI 0.49–0.85), (3) when a dose of omega −3 fatty acids ≥2000 mg/d was applied (RR 0.61 95% CI 0.45–0.81), (4) in wheeze/asthma without sensitivity (RR 0.71 95% CI 0.54–0.94). Conclusion: The available low-quality evidence indicated that omega-3 fatty acids supplementation during pregnancy may reduce the incidence of wheeze/asthma of children, but incidence of asthma was not reduced after omega-3 fatty acids supplementation during pregnancy. More well-designed RCTs with large sample sizes need to be conducted to better understand the effectiveness of omega-3 fatty acids supplementation during pregnancy with asthma in childhood.
Adoption and maintenance of physical activity: Planning interventions in young, middle-aged, and older adults

Young, middle-aged, and older adults in orthopaedic outpatient rehabilitation (N = 373) were randomly assigned to either an interviewer-assisted or a standard-care self-administered planning intervention. Physical activity planning consisted of specifying action plans to facilitate action initiation, and coping plans to overcome barriers. The interviewer-assisted condition led to more complete action plans and a longer duration of physical activities up to six months after discharge. Regarding coping planning, older and middle-aged adults benefited more from interviewer-assisted planning while younger adults benefited more from self-administered planning. Planning as such was found to be an effective tool for enactment irrespective of chronological age. The delayed effect of coping planning on enactment suggests that coping planning is important for long-term maintenance.
Differential expression of SOCS1 in macrophages in relapsing‐remitting and chronic EAE and its role in disease severity

Experimental autoimmune encephalomyelitis (EAE) is a T cell‐mediated neuroinflammatory disease that is often used as a model of multiple sclerosis. EAE can follow either relapsing‐remitting (RR) or chronic (CH) courses, yet the factors responsible for differentially inducing these forms of disease remain largely unknown. Proinflammatory cytokines play an important role in EAE, and signaling by these cytokines can be negatively regulated by the suppressor of cytokine signaling 1 protein (SOCS1). We assessed if differential expression of SOCS1 could contribute to the clinical course of RR and CH forms of EAE induced in the same mouse strain (C57BL/6) using the same myelin antigen (myelin oligodendrocyte glycoprotein). We show that SOCS1 mRNA levels are significantly elevated in the spinal cord in early stages of both RR‐ and CH‐EAE. SOCS1 protein is highly expressed in immune cells in EAE lesions in the spinal cord, with expression predominantly localized within macrophages. Importantly, the number of Mac‐1+ macrophages expressing SOCS1 at the peak stage of RR disease is three‐fold greater than in CH‐EAE. Furthermore, the macrophage effector molecule iNOS, whose expression is regulated by SOCS1, is significantly reduced at the peak of RR‐ versus CH‐EAE. Finally, the administration of a SOCS1‐mimetic peptide reduces disease severity in the CH‐EAE model. Thus, the differential expression of SOCS1 may contribute to the development of RR and CH forms of EAE. © 2010 Wiley‐Liss, Inc.
Urinary Neopterin in Patients with Diabetes Mellitus and Foot Ulcers

Abstract Increased urinary or serum concentrations of neopterin have been reported in disorders associated with systemic immune activation, e.g. viral infections, cancer, or autoimmune diseases, but the data on neopterin concentrations in patients with diabetes mellitus are limited. The aim of the present study was to investigate urinary neopterin concentrations in patients with diabetes mellitus and with or without diabetic foot. Urinary neopterin was determined by high-performance liquid chromatography in 51 patients with diabetes mellitus, including 19 patients with diabetic foot, and 18 healthy controls. Neopterin concentrations were significantly increased in patients with diabetes mellitus compared to controls (mean ± standard deviation; 221 ± 149 vs. 139 ± 66 μmol/mol creatinine; Mann-Whitney U test, p = 0.003). Urinary neopterin concentrations in patients with or without diabetic foot were identical (224 ± 113 vs. 219 ± 169 μmol/mol creatinine). No significant difference was also observed between patients with type 1 and type 2 diabetes mellitus, between patients treated with insulin compared to patients not treated with insulin, patients with or without diabetic retinopathy, with or without diabetic neuropathy, with or without diabetic nephropathy, with or without ischemic heart disease, with or without ischemic disease of lower extremities, and with or without ischemic cerebrovascular disease. Atrend of higher neopterin concentrations was observed in patients with any complication of diabetes compared to no complications (234 ± 164 vs. 176 ± 73 μmol/mol creatinine), and compared to controls, urinary neopterin was significantly increased only in patients with complications. No significant correlation was observed between urinary neopterin and glycosylated hemoglobin (rs = - 0.14, p = 0.39) or the duration of diabetes (rs = 0.25, p = 0.09). In conclusion, present results demonstrate that urinary neopterin is increased in patients with diabetes mellitus. No differences were observed in urinary neopterin concentrations based on type of diabetes, therapy or presence of diabetic foot, and urinary neopterin did not correlate with the glycosylated hemoglobin levels or duration of diabetes. Increased urinary neopterin concentrations in patients with diabetes mellitus is associated with the presence of complications and may reflect systemic immune activation associated with atherosclerosis.
N-acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin-induced diabetic rats.

BACKGROUND AND OBJECTIVE The purpose of this study was to evaluate the morphometric and histopathological changes associated with experimental periodontitis in diabetic rats in response to systemic administration of N-acetylcysteine (NAC), a sulfhydryl-containing thiol antioxidant. MATERIAL AND METHODS Sixty Wistar rats were divided into six experimental groups: nonligated (NL) group; ligature-only (L) group; streptozotocin-only (STZ) group; STZ and ligature (STZ + L) group; and systemic administration of NAC and ligature (70 and 100 mg/kg body weight per day, respectively) (NAC70 and NAC100 groups). Diabetes mellitus was induced by 60 mg/kg of streptozotocin. Silk ligatures were placed at the gingival margin of the lower first molars of the mandibular quadrant. The study duration was 30 d and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined to assess the differences among the study groups. RESULTS At the end of the 30-d study period, alveolar bone loss was significantly higher in the STZ + L group compared with the other groups (p < 0.05). Also, alveolar bone loss in all the NAC groups was significantly lower than in the STZ + L and L groups (p < 0.05). The osteoblastic activity in the NAC100 group was significantly higher than in the other groups (p < 0.05). CONCLUSION Within the limits of this study, it can be suggested that NAC, when administered systemically, prevents alveolar bone loss in the diabetic rat model.
S100B attenuates microglia activation in gliomas: Possible role of STAT3 pathway

Despite significant infiltration into tumors, the effector function of macrophages (MPs) and microglia (MG) appears to be suppressed in gliomas. Although STAT3 pathway is thought to play a role in this process, the exact mechanism by which gliomas induce STAT3 activation in MPs and MG is not known. Because activation of receptor for advanced glycation end products (RAGE) can induce STAT3, and because gliomas express high levels of S100B, a RAGE ligand, we hypothesized that MP/MG STAT3 activity may be modulated through S100B‐RAGE interaction. Exposure of N9 MG and bone marrow‐derived monocytes (BMM) to GL261 glioma condition medium (GCM) and low (nM) levels of S100B increased RAGE expression, induced STAT3 and suppressed MG function in vitro. Furthermore, neutralization of S100B in GCM, partially reversed IL‐1β suppression in BMM, suggesting that the inhibitory effect of GCM to be in part due to S100B. Finally, blockage of S100B‐RAGE interaction inhibited STAT3 activation in N9 MG and in glioma MG/MP in vivo. These findings suggest that the RAGE pathway may play an important role in STAT3 induction in glioma‐associated MG/MPs, and that this process may be mediated through S100B. © 2010 Wiley‐Liss, Inc.
Gynecomastia in adolescents

Purpose of review Gynecomastia is a common finding in adolescent men. The primary care provider should feel equipped to thoroughly evaluate this condition and to differentiate physiologic from pathologic breast enlargement. The present review focuses on the epidemiology, pathogenesis, evaluation, and treatment of gynecomastia during adolescence. Recent findings While gynecomastia has long been attributed to an imbalance between estrogen and androgen concentrations, recent literature has begun to illuminate other potential mechanisms for breast development in adolescent men. Increased leptin levels, as well as human chorionic gonadotropin and luteinizing hormone receptors on male breast tissue, may play a role. Newer treatment strategies, such as the antiestrogen raloxifene, have shown promising results; however, further studies are needed to determine long-term efficacy. As a result of the limited pharmaceutical treatment options, many more adolescents are seeking surgical intervention. Summary Gynecomastia is frequently encountered in the primary care setting. During adolescence, male breast enlargement is most often benign and rarely represents a pathologic mechanism. Careful attention should be paid to both the breast and testicular examination. A detailed history should include an inquiry regarding the use of illicit substances, anabolic–androgenic steroids, herbal products, and medications. The impact of gynecomastia on the adolescent's mental health should be assessed. A workup for pathologic causes is rarely required. Reassurance remains the standard of care for physiologic gynecomastia.
Unmet needs in the cardiologic and neurologic work-up of left ventricular hypertrabeculation/noncompaction

ABSTRACT Introduction: Left-ventricular hypertrabeculation/noncompaction (LVHT) is a rare myocardial abnormality of the distal left ventricular myocardium, which may be complicated by functional abnormalities such as heart failure, arrhythmias, or thrombus formation. Area covered: This review discusses unsolved issues concerning LVHT, such as the lack of uniformly accepted diagnostic criteria, the unclear pathogenesis of LVHT, the relevance of clinical manifestations of LVHT as prognostic factors, the unclear association between LVHT and neuromuscular disorders, and the question which therapy LVHT patients should receive. Expert commentary: Despite controversy about these unsolved issues, there is consensus, however, that investigations need to be encouraged and undertaken which address the many open questions. This may help to prevent misdiagnosing or overdiagnosing LVHT, clarify etiology and pathomechanisms of LVHT, estimate the prognosis and outcome of these patients, identify the relevance of the association with certain neuromuscular disorders, chromosomal defects, and mutations, and to provide the optimal treatment and care.
Riboflavin‐mediated cellular photoinhibition of cisplatin‐induced oxidative DNA breakage in mice epidermal keratinocytes

Background/purpose: Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of various kinds of malignant tumors. A major drawback associated with cisplatin chemotherapy is its cytotoxicity/genotoxicity towards normal tissues. The cytotoxicity has been attributed, in part, to the oxidative stress generated by the drug. Riboflavin is a micronutrient known for its photosensitization characteristics. Owing to the emergence of photodynamic therapy as a modality for the treatment of solid tumors and other accessible lesions in terms of opthalmic, dermatological, cardiovascular and urological diseases, the therapeutic window of riboflavin as a sensitizer has been used to avoid the toxic side effects of cisplatin.
Sports-related concussions in pediatrics

Purpose of review Mild traumatic brain injury (mTBI) accompanied by concussion is a common presenting complaint among children presenting to emergency departments (EDs). There is wide practice variation regarding diagnosis and management of sports-related concussions in children. Our aim is to review the most recent evidence and expert recommendations regarding initial diagnosis and management of sports-related concussions in children. Recent findings Previous classifications and return-to-play guidelines for sports-related concussions in children were inadequate and have been abandoned. The most recent recommendations, from the Third International Conference on Concussion in Sport (CIS), reinforce an individualized evaluation of the athlete's neurocognitive functioning, symptoms and balance. They further reinforce a step-wise approach in the return-to-play process once neurocognitive function has returned to baseline and all symptoms have resolved. The need for a standardized and objective tool to aid in the initial evaluation and diagnosis of mTBI in the clinical setting led to the development of the Acute Concussion Evaluation (ACE) protocol, which is currently being modified for specific use in the ED. Computed tomography (CT) in the acute setting is not likely to be useful for children with mTBI. Newer functional imaging techniques may prove relevant in the future. Summary Further research on both the incidence of sports-related concussions in children and management paradigms is needed. The role of novel imaging modalities in clinical assessment also needs to be elucidated. An individualized approach to evaluation and management of sports-related concussions is recommended. It should incorporate standard symptom assessment, neuropsychological testing and postural stability testing.
Cerebellar oligodendroglial cells have a mesencephalic origin

While the origin of oligodendroglia in the prosencephalon and spinal cord has been extensively studied and accurately described, the origin of this cell type in the cerebellum is largely unknown. To investigate where cerebellar oligodendrocytes generate and which migratory pathways they follow to reach their final destination in the adult, in ovo transplants were performed using the quail/chick chimeric system. The chimeric embryos were developed up to HH43‐49 (17–19 days of incubation) to map the location of donor cells and analyze their phenotype by immunohistochemistry. As a result, mesencephalic homotopic and homochronic transplants generated cellular migratory streams moving from the grafted epithelium into the host cerebellum, crossing the isthmus mainly through the velum medullare and invading the central white matter. From here, these mesencephalic cells invaded all the layers of the cerebellar cortex except the granular layer. The majority of the cells were detected in the central and folial white matter, as well as in superficial regions of the internal granular layer, surrounding the Purkinje cells. In the latter case, the donor cells presented a Bergmann glial morphology and were Vimentin positive, while in other areas they were PLP and Olig2‐positive, indicating an oligodendroglial fate. The combinatory analysis of the different grafts allowed us to propose the fate map of chick cerebellar oligodendroglia at the neural tube stage. As a result, the majority of the cerebellar oligodendrocytes originate from the parabasal plate of the mesencephalon. © 2011 Wiley‐Liss, Inc.