Immune tolerance induced in the anterior chamber ameliorates corneal transplant rejection.

The relevance of regulatory T cells (Tregs) in induction of tolerance against corneal allografts has been well established. However, whether Tregs can be induced in the anterior chamber and suppress local alloimmune response after corneal transplantation is largely unknown. In the current study we report that not only can alloantigen specific Tregs be generated in the anterior chamber during corneal transplantation, they also play important roles in suppressing allograft rejection. Allograft rejected mice exhibit reduced Treg induction in the anterior chamber and the ability of aqueous humor and corneal endothelial cells from allograft rejected mice to induce Tregs is compromised. Further analysis revealed that the expression of immune-tolerance-related molecules is significantly decreased. Finally, we demonstrate that increasing Treg cells specifically in the anterior chamber can effectively suppress allograft rejection and exhibits better efficacy in promoting corneal allograft survival than systemic administration of Treg cells. Our current study may provide new ideas for the prevention and treatment of corneal transplant rejection.

Targeting NF-κB c-Rel in regulatory T cells to treat corneal transplantation rejection.

The relevance of Tregs in the induction of tolerance against corneal allografts has been well established. Although it is well known that the conversion of Tregs into effector-like cells contributes to the loss of corneal immune privilege, the underlying mechanism is still not fully understood. Using heterologous penetrating keratoplasty model, we found that Tregs from corneal allograft rejected mice (inflam-Tregs) exhibit impaired function and characteristics of effector T cells. Further study showed that the expression of NF-κB c-Rel, a key mediator of effector T cell function, was significantly increased in inflam-Tregs. Mechanistic study revealed that elevated NF-κB c-Rel level in inflam-Tregs impaired Treg function through the promotion of inflammatory cytokine production and glycolysis. More importantly, we demonstrated that targeting NF-κB c-Rel was able to improve the immune suppressive function of inflam-Tregs in vitro and enhance the potential of them to suppress corneal transplantation rejection. Therefore, our current study identified NF-κB c-Rel as a key mediator of the conversion of Tregs into effector-like cells when under inflammatory environment.

Effects of Sodium Valproate Combined with Lamotrigine on Quality of Life and Serum Inflammatory Factors in Patients with Poststroke Secondary Epilepsy.

BACKGROUND: We sought to explore the effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy. METHODS: A total of 145 patients with post-stroke secondary epilepsy admitted to our hospital from January 2017 to June 2018 were collected: 76 treated with sodium valproate combined with lamotrigine (study group) and 69 patients treated with sodium valproate alone (control group). The levels of serum high-mobility group protein B1, matrix metalloproteinase 9, and interleukin 6 were detected before and after treatment, and the therapeutic efficacy and adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the study group was higher than that of the control group. Both groups decreased in epileptiform discharges or in the number of involved leads after treatment, with the results of the study group being lower than those of the control group. The quality of life scores in both groups was increased after treatment, albeit the scores of the study group were higher than those of the control group. In terms of the levels of serum inflammatory factors, the 2 groups were reduced after treatment; the levels of the study group were lower than those of the control group. Regarding the incidence of adverse reactions, no significant difference was seen between the 2 groups. CONCLUSIONS: Sodium valproate combined with lamotrigine has better clinical efficacy and higher safety in the treatment of poststroke secondary epilepsy and is able to reduce the expression levels of serum inflammatory factors.

The Promising Effects of Transplanted Umbilical Cord Mesenchymal Stem Cells on the Treatment in Traumatic Brain Injury.

Many studies have reported the recovery ability of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord-derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical cord immediately after delivery. The traumatic brain injury (TBI) model was formed by the classical gravity method. The authors detected the behavior changes and measured the levels of inflammatory factors, such as interleukin-lß and tumor necrosis factor-α by enzyme linked immunosorbent assay (ELISA) at 1, 2, 3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs. Simultaneously, the expression of glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time-polymerase chain reaction and ELISA.The authors found that the group of transplantation UC-MSCs has a significant improvement than other group treated by phosphate buffered saline. In the behavioral test, the Neurological Severity Scores of UC-MSCs + TBI group were lower than TBI group (P < 0.05), but not obviously higher than control group at 2, 3, and 4week, respectively. The inflammatory factors are significantly reduced comparison with TBI group (P < 0.05), but both GDNF and BDNF were higher than TBI group (P < 0.05). The results indicated that UC-MSCs might play an important role in TBI recovery through inhibiting the release of inflammatory factors and increasing the expression of GDNF and BDNF.

NF-κB c-Rel Is a Potential Therapeutic Target for Acute Corneal Transplant Rejection.

Purpose: The purpose of this study was to determine the role of nuclear factor kappa B (NF-κB) c-Rel during acute corneal transplant rejection and whether targeting c-Rel can reduce corneal transplant rejection. Methods: Allogeneic corneal transplantation was performed in wild-type and c-Rel-deficient mice. Corneal graft survival rate, opacity, neovascularization, and edema were evaluated by slit-lamp microscopy. Adeno-associated virus 6 (AAV6) expressing c-Rel-specific small hairpin RNA (AAV6-shRel) and the small-molecule compound pentoxifylline (PTXF) were used to reduce c-Rel expression. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. c-Rel expression was determined by quantitative RT-PCR and western blot. The effect of c-Rel inhibition on corneal transplant rejection was examined using a mouse model of acute allogeneic corneal transplantation. Tear production and corneal sensitivity were measured to determine the potential toxicity of AAV6-shRel and PTXF. Results: The expression of c-Rel and its inflammatory targets was increased in both mice and patients with corneal transplant rejection. Loss of c-Rel reduced corneal transplant rejection in mouse. Both AAV6-shRel and PTXF were able to downregulate the expression of c-Rel and its inflammatory targets in vitro. Treatment with AAV6-shRel or PTXF reduced corneal transplant rejection in mouse and downregulated the expression of inflammatory cytokines in peripheral blood mononuclear cells from patients with corneal transplant rejection. Treatment with AAV6-shRel or PTXF displayed no side effects on tear production or corneal sensitivity. Conclusions: Increased expression of c-Rel is a risk factor for acute corneal transplant rejection, and targeting c-Rel can efficiently reduce corneal transplant rejection.

Relationship between serum Th1/Th2 imbalance and depression in elderly patients with COPD and its clinical implications.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes organic damage as well as anxiety, depression, fear, and other psychological disorders, which seriously affect the quality of life and prognosis of patients and cause a huge economic burden to the family and society. OBJECTIVE: The aim of this study was to investigate the correlation between an imbalance of serum Th1/Th2 indicators and psychiatric depression in elderly patients with COPD and analyze its implications for clinical management. METHODS: From January 2018 to May 2022, 120 elderly patients with COPD treated at our hospital were categorized into two groups based on the self-rating depression scale (SDS): COPD with depression (SDS score ⩾ 50) and COPD alone (SDS score < 50). Blood gas analysis, pulmonary function, and serum Th1/Th2 index were determined. Receiver operating characteristic (ROC) curves were analyzed to explore the diagnostic value of serum Th1/Th2 ratios for COPD complicated by depression. RESULTS: Compared with the group without depression, the partial pressure of carbon dioxide and COPD assessment test scores were significantly higher, and the oxygenation index, forced expiratory volume in one second (FEV1), and percent predicted FEV1 were significantly lower in the COPD with depression group (P< 0.05). Interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were significantly higher in the COPD with depression group than in the group without depression (P< 0.05). Logistic regression analysis indicated that the imbalance of serum IL-1ß, IL-2, IL-6, IL-8, IL-10, and TNF-α was a risk factor for mental depression in elderly patients with COPD. When comparing prognostic indices, the interval before the first onset of clinically noticeable deterioration (CID-C) in the COPD with depression group was noticeably shorter than that in the COPD without depression group; the incidence of CID-C within 6 months was noticeably higher in the COPD with depression group than in the group without depression. CONCLUSION: Elderly patients with COPD and depression had reduced pulmonary function and higher serum Th1/Th2 levels, and an imbalance in serum Th1/Th2 indicators was a potential risk factor for depression. Moreover, elderly patients with COPD and depression were at a higher risk of disease progression and had a worse prognosis. Thus, an imbalance in serum Th1/Th2 indicators is a potential prognostic factor for evaluating depression in patients with COPD.

Maternal infection during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring: A systematic review and meta-analysis.

BACKGROUND: The effects of maternal infection during pregnancy on the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring are unclear, and no overview is available. METHODS: We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. RESULTS: We found that that maternal infection during pregnancy was associated with a small increase in the risk of ADHD (OR 1.25, 95% CI 1.09, 1.44, P < 0.0001; I2 = 92.9%, p < 0.0001) in the offspring. In subgroup analyses, the association remained for maternal genitourinary (GU) infection (OR, 1.19, 1.12, 1.27, P < 0.001; I2 = 0%; p = 0.517). However, there was no significant association when we pooled data from siblings from other pregnancies (OR = 1.06, 95% CI, 0.99-1.13, P = 0.084; I2 = 0%; p = 0.859), implying that the association was due to confounding. CONCLUSIONS: The statistically significant association between maternal infection during pregnancy and ADHD in the offspring can be partially explained by unmeasured confounding.

Nasal-type extranodal natural killer/T-cell lymphoma with oral ulcer as the earliest clinical manifestation.

Nasal-type extranodal natural killer/T-cell lymphoma (ENKTL-NT) is a special subtype of non-Hodgkin's lymphoma derived from natural killer cells or cytotoxic T cells. Oral ulcers as the first symptom makes its diagnosis challenging because of its rarity and lack of understanding. We report a case of ENKTL-NT in this paper. We analyzed the clinicopathological features, differential diagnosis, treatment, prognosis and the causes of misdiagnosis to provide a diagnostic basis for dentists to make better clinical diagnosis and treatment.

Positive psychological intervention for anxiety, depression and coping in subjects addicted to online games.

BACKGROUND: Addiction to online games is not uncommon. The patients usually refuse to take medications and present with affective symptoms such as anxiety, depression and negative coping styles. Psychological intervention based on positive psychology is a promising treatment for such patients. AIM: To evaluate the effect of positive psychological intervention on anxiety, depression and coping in people addicted to online games. METHODS: This self-controlled study included 89 people addicted to online games, who received treatment at Hangzhou Seventh People's Hospital, Hangzhou, China in 2019. The Hamilton Anxiety Scale, Hamilton Depression Scale and Trait Coping Style Questionnaire were administered to evaluate the anxiety, depression and coping style among these people. Psychological intervention based on positive psychology was provided for 6 wk followed by another evaluation. The results were compared against those from the previous evaluation. RESULTS: After 6 wk of psychological intervention, 89 people achieved a significant improvement in the Hamilton Anxiety Scale and Hamilton Depression Scale-24 scales. The score for positive coping style in Trait Coping Style Questionnaire was significantly improved, while that of the negative coping style decreased significantly (P < 0.05). CONCLUSION: Psychological intervention based on positive psychology alleviated affective symptoms, such as anxiety and depression, in subjects addicted to online games. Psychological intervention corrected negative coping style, thereby improving mental health.

Exposure to general anaesthesia in childhood and the subsequent risk of attention-deficit hyperactivity disorder: A meta-analysis of cohort studies.

BACKGROUND: The evidence for a relationship between general anaesthesia induced in childhood and the risk of attention-deficit hyperactivity disorder (ADHD) in later life is inconsistent. We systematically assessed whether such an association existed. METHODS: We searched the PubMed and EMBASE databases for relevant cohort studies. Relative risks (RRs) and 95 % confidence intervals (CIs) were calculated to determine the relationship between induction of childhood general anaesthesia and the risk of ADHD in later life. RESULTS: Seven studies (eight publications) on developmental outcomes after the induction of childhood general anaesthesia met our inclusion criteria but not our exclusion criteria. Repeat childhood general anaesthesia (RR = 1.84, 95 CI% 1.14-2.97; P < 0.001; I2 = 74.8 %), but not one-off general anaesthesia (RR = 1.09, 95 CI% 0.93-1.27; P = 0.301; I2 = 0%), was associated with an increased risk of ADHD in later life. The association was evident only when the total general anaesthesia exposure exceeded 90 min. CONCLUSIONS: Our meta-analysis indicated that the effect of general anaesthesia on the risk of ADHD is dose- or duration-dependent.

MicroRNA-21 Regulates Diametrically Opposed Biological Functions of Regulatory T Cells.

Regulatory T cells (Tregs) are considered important for controlling the onset and development of autoimmune disease. Although studies have shown that miR-21 is expressed at higher levels in Treg cells, it remains largely elusive whether miR-21 regulates the immune-suppressive function of Tregs. In the current study, we generated mice lacking miR-21 specifically in their Tregs and investigated the role of miR-21 in regulating Treg function both in vitro and in vivo. Our study revealed that Tregs lacking miR-21 exhibit normal phenotype and unaltered function in suppressing T cell proliferation and dendritic cell activation in vitro. However, compared with miR-21-sufficient Tregs, they produce significant more IL-17 and IL-10 when under pathogenic Th17-priming condition. Adenoviral delivery of miR-21 into Treg cells is able to reduce the expression of both IL-17 and IL-10. Mechanistic study revealed that miR-21 down-regulates IL-10 expression through direct targeting of IL-10, and suppresses reprogramming of Tregs into IL-17-secreting cells through down-regulating Stat3 activity. However, we detected no significant or marginal difference in the development of various autoimmune diseases between wild type mice and mice with Treg-specific deletion of miR-21. In conclusion, our study demonstrated that miR-21 in Tregs regulates diametrically opposed biological Treg functions and is largely dispensable for the development of autoimmune disease.

Dissolved organic matter-mediated photodegradation of anthracene and pyrene in water.

Toxicity and transformation process of polycyclic aromatic hydrocarbons (PAHs) is strongly depended on the interaction between PAHs and dissolved organic matters (DOM). In this study, a 125W high-pressure mercury lamp was used to simulate the sunlight experiment to explore the inhibition mechanism of four dissolved organic matters (SRFA, LHA, ESHA, UMRN) on the degradation of anthracene and pyrene in water environment. Results indicated that the photodegradation was the main degradation approach of PAHs, which accorded with the first-order reaction kinetics equation. The extent of degradation of anthracene and pyrene was 36% and 24%, respectively. DOM influence mechanism on PAHs varies depending upon its source. SRFA, LHA and ESHA inhibit the photolysis of anthracene, however, except for SRFA, the other three DOM inhibit the photolysis of pyrene. Fluorescence quenching mechanism is the main inhibiting mechanism, and the binding ability of DOM and PAHs is dominantly correlated with its inhibiting effect. FTIR spectroscopies and UV-Visible were used to analyze the main structural changes of DOM binding PAHs. Generally, the stretching vibration of N-H and C-O of polysaccharide carboxylic acid was the key to affect its binding with anthracene and C-O-C in aliphatic ring participated in the complexation of DOM and pyrene.

Anti-leucine-rich Glioma Inactivated-1 Encephalitis Associated with Essential Thrombocythemia.

Anti-leucine-rich glioma inactivated-1 (anti-LGI1) encephalitis is a subgroup of autoimmune encephalitis. We herein report the case of a 60-year-old man who presented with typical symptoms, including short-term memory loss, mental abnormalities, hyponatremia and seizures characterized by faciobrachial dystonic seizures and who was diagnosed with anti-LGI1 encephalitis. At the same time, he was diagnosed with essential thrombocythemia. A significant improvement was obtained by treatment with corticosteroid, immunoglobulin, mycophenolate mofetil, and hydroxyurea. Autoimmune diseases are associated with a significantly increased risk of developing myeloproliferative neoplasms, which may explain the coexistence of anti-LGI1 encephalitis and essential thrombocythema in this patient; however, but more cases and studies are needed to determine whether there is any correlation between these conditions.

Effect of dissolved organic matter fractions on photodegradation of phenanthrene in ice.

The effect of dissolved organic matter (DOM) fractions on photodegradation of phenanthrene (PHE) in ice was investigated. DOM in surface water and wastewater samples was fractionated using XAD-8/XAD-4 resins into five fractions: hydrophobic acid (HPO-A), hydrophobic neutral (HPO-N), transphilic acid (TPI-A), transphilic neutral (TPI-N) and hydrophilic fraction (HPI). The photodegradation rate of PHE in ice was about 40% greater than that in water. The screening effect and quenching effect contributed 3-12% and 88-97% toward the inhibition of DOM fractions on PHE photodegradation in ice, respectively. The contribution ratios of singlet oxygen (1O2) and hydroxyl radical (OH) produced from DOM fractions to PHE photodegradation rates in ice were 9-31% and 2-13%, respectively. Among five DOM fractions, HPO-A was most efficient in advancing PHE photodegradation in ice through 1O2 mechanism. When excluding the photosensitized effect of 1O2 and OH produced from DOM fractions, the quencing effect of DOM fractions on PHE photodegradation in ice was closely related to their PHE binding ability.

TDAG51 in the anterior temporal neocortex of patients with intractable epilepsy.

TDAG51 (T cell death-associated gene 51) is an apoptosis-associated protein. Our aim was to investigate TDAG51 expression in the anterior temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of TDAG51 in IE. Tissue samples from the anterior temporal neocortex of 33 patients who had surgery for IE were used to detect TDAG51 expression by immunohistochemistry, immunofluorescence, and Western blotting. We compared these tissues with nine histologically normal anterior temporal lobes from intracranial hypertension patients who had decompression procedures. TDAG51 was mainly expressed in the cytoplasm of neurons and glial cells. TDAG51 in IE was significantly higher than that in the controls. These findings were consistently observed using Western blotting, immunofluorescence, and immunohistochemistry techniques. TDAG51 in patients with IE was significantly higher when compared with levels in the controls. This finding suggests TDAG51 is consistent with a possible role of this gene in the evolution of the pathology in IE.

miR­140­5p regulates angiogenesis following ischemic stroke by targeting VEGFA.

MicroRNA (miRNA or miR) expression profiles are altered in tissues under hypoxic-ischemic conditions. The expression of miR­140 is downregulated >2-fold following hypoxic-ischemic brain damage, however, its role in angiogenesis subsequent to cerebral ischemia is not fully understood. The present study aimed to investigate the role of miR-140-5p in angiogenesis and the molecular mechanism mediated by vascular endothelial growth factor A (VEGFA) in an in vitro model for brain ischemia. A rat middle cerebral artery occlusion (MCAO) model was constructed, and the results from reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that the expression levels of miR-140­5p were significantly decreased, while the expression levels of VEGFA were significantly increased between 12 and 48 h in the rat cerebral following MCAO. Furthermore, human umbilical vein endothelial cells (HUVECs) were exposed to low oxygen conditions and it was demonstrated that hypoxia downregulated miR-140-5p and upregulated VEGFA expression levels. The miR-140-5p mimic was transfected into the normoxic and hypoxic HUVECs and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Transwell migration and tube formation assays were performed. The results indicated that miR­140­5p inhibited angiogenesis by decreasing cell proliferation, migration and tube formation. Additionally, in human embryonic kidney 293 cells, results from the luciferase reporter assay revealed that miR­140­5p directly targeted the 3' untranslated region of VEGFA and that miR­140­5p regulated the protein expression of VEGFA. To further analyze this effect, a VEGFA­pEGFP­C1 plasmid was transfected into the normoxic and hypoxic HUVECs, and it was revealed that the inhibitory effect of miR­140­5p on angiogenesis was attenuated by the overexpression of VEGFA. In conclusion, to the best of our knowledge, the present study is the first to suggest that miR­140­5p exerts an inhibitory effect on angiogenesis in an in vitro model of ischemia, and this effect is achieved partially by targeting VEGFA. The present study provided a novel biomarker for the treatment of cerebral ischemia.

Identification of serum miRNAs differentially expressed in human epilepsy at seizure onset and post-seizure.

MicroRNAs (miRNAs) function as potential novel biomarkers for disease detection due to their marked stability in the blood and the characteristics of their expression profile in several diseases. In the present study, microarray­based serum miRNA profiling was performed on serum obtained from three patients with epilepsy at diagnosis and from three healthy individuals as controls. This was followed by reverse transcription­quantitative polymerase chain reaction analysis in a separate cohort of 35 health volunteers and 90 patients with epilepsy. The correlations between miRNAs and clinical parameters were analyzed. The array results showed that 15 miRNAs were overexpressed and 10 miRNAs were underexpressed (>2­fold) in the patients with epilepsy. In addition, four miRNAs, including miR­30a, miR­378, miR­106b and miR­15a were found to be overexpressed in the serum of patients at seizure onset, compared with post­seizure. When the patients were at seizure onset, the expression of miR­30a was positively associated with seizure frequency. No significant differences were found between miR­30a and gender, age or number of years following diagnosis. The expression levels of miR­378, miR­106b and mir­15a were not associated with the clinical parameters in the patients with seizures. Calcium/calmodulin­dependent protein kinase type IV was a target of miR­30a, and its expression was increased following seizure and was negatively correlated with miR­30a in the patients with epilepsy. The present study provided the first evidence, to the best of our knowledge, that the expression levels of miR­378, miR­30a, miR­106b and miR­15a were enhanced in epileptic patients with seizures. miR-30a may be useful for prognostic prediction in epilepsy.

Echinoderm microtubule-associated protein -like protein 5 in anterior temporal neocortex of patients with intractable epilepsy.

OBJECTIVES: EMAP-like Protein 5 (EML5) is a new echinoderm microtubule-associated protein that is expressed in the central nervous system. The aim of this study was to investigate the expression profile of EML5 in the anterior temporal neocortex of patients presenting with intractable epilepsy (IE). MATERIALS AND METHODS: Western blot assays were performed to determine EML5 expression in 36 surgically resected anterior temporal neocortices of patients with IE and eight control tissues. Immunohistochemistry and immunofluorescence were employed to explore protein expression in IE. RESULTS: EML5 was highly expressed in both neurons and glial cells of the anterior temporal neocortex of IE patients, whereas only low levels of EML5 were detected in control brain tissues. Western blotting showed an enhanced expression of EML5 protein in the anterior temporal neocortex of IE (optical density (OD) = 1.8030 ± 0.1335/1.1852 ± 0.2253, P<0.05) compared with normal control tissues. CONCLUSION: The results demonstrate that highly expressed EML5 in the neurons and glial cells of the cortex of patients with epilepsy is associated with microtubular dysfunction after frequent and recurrent seizures.

[Studies on anti-hyperglycemic effect and its mechanism of Dendrobium candidum].

OBJECTIVE: To study the anti-hyperglycemic effect and its mechanism of Dendrobium candidum (DC). METHOD: Normal mice, adrenaline-induced hyperglycemic mice, streptozotocin-induced diabetic (STZ-DM) rats were used. The mechanisms of the anti-hyperglycemic action were studied with radio-immunoassay, immunohistochemical HRP-SPA stain, etc. RESULT: DC could not obviously decrease the serum glucose concentrations and insulin levels in normal mice. It could increase serum insulin levels and decrease serum glucagons concentrations in STZ-DM rats. The results of immunohistochemical stain demonstrated that the number of islet beta cells was increased and that of islet a cells was decreased in STZ-DM rats. It could also decrease the serum glucose concentrations and increase liver glucogen contents in adrenaline-induced hyperglycemic mice. CONCLUSION: DC has obvious anti-hyperglycemic effects in adrenaline-induced hyperglycemic mice and STZ-DM rats. Its mechanisms are stimulating the secretion of insulin from beta cells and inhibiting the secretion of glucagons from a cells, and it can probably decrease the decomposition of liver glucogen and increase the synthesis of liver glucogen.