Orogenital ulcers and the Behcet’s disease

Behcet’s’s disease is a systemic vasculitis involving small to large veins and arteries. It is a sporadic disease, mostly prevalent among the ancestors of the silk route. It is characterized by recurrent oral ulcers, genital ulcers, and uveitis. It also can manifest as skin, vascular, gastrointestinal, neurological, cardiac, and renal involvement. Though overall mortality is around 5%, delay in diagnosis and treatment may lead to significant morbidity. Cardiovascular and pulmonary arterial aneurysms are dreadful complications of this disease. Being uncommon in south India it is liable to be wrongly diagnosed and treated. Delay in the diagnosis and treatment may lead to severe complications. Here we present a case of Behcet’s disease which was managed at primary health care inadequately. We also demonstrated a quick response to steroids which are the mainstay of treatment. In this case presentation we illustrated pre and post treatment scrotal and oral Behcet’s’s lesions for clinicians to memorize. We also discussed international criteria to diagnose Behcet’s disease (ICBD) in concurrence with our case. In this presentation, we briefly described the involvement of other systems and their treatment. This article also elaborated on the latest developments in the treatment of Behcet’s disease.

Development and verification of a rapid detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line / 中国生物制品学杂志

@#Objective To develop and verify a rapid detection method for the biological activity of adalimumab based on U937-NF-κB-Luc cell line. Methods Using U937-NF-κB-Luc cell line as the detection cells,a method for detecting the biological activity of adalimumab was developed based on luciferase luminescence principle. The method was optimized for the concentration of tumor necrosis factor-α(TNF-α)(160 ng/mL as initial concentration,2 times serial dilution,10dilutions),the initial concentration of antibody(2 000 ng/mL,2 times serial dilution,20 dilutions),the dilution multiple of antibody(1. 5,2,3,4 times),the inoculation amount(8 × 103,2 × 104,4 × 104,6 × 104cells/well)and the incubation time(0. 5,1,2,3 h),and verified for the specificity,accuracy,precision and linear range. The relative potency of five batches of adalimumab was detected by using the optimized method and TNF-α neutralization activity method based on L929cells respectively. Results The dose-response curve of adalimumab international standard showed a typical S-type,and the data complied with the four-parameter equation y =(A-D)/[1 +(x/C)B]+ D,R2> 0. 99. The optimum concentration of TNF-α was 5 ng/mL,the initial concentration of antibody was 800 ng/mL,the dilution ratio for adalimumab was 1∶2,the inoculation amount was 2 × 104cells/well,and the induction time was 2 h. Three therapeutic monoclonal antibodies of TNF-α target,such as adalimumab,obtained good dose-response curves,while therapeutic monoclonal antibodies of other non-TNF-α targets did not show this curve. The linear regression equation of the logarithmic value of theoretical potency and the logarithmic value of the corresponding measured potency had a slope of 1. 037,and the relative bias was within the range of ± 12%. The geometric coefficient of variation(GCV)of the relative titer measured value of each sample was less than20%. The theoretical potency ranged from 64% to 156%,showing a good linear relationship with the measured values,and the fitting linear regression equation was y = 1. 037 4 x-0. 023 7,R2= 0. 998 4. There was no significant difference in the relative potency measured results of five batches of adalimumab by the two methods(t = 1. 198,P = 0. 265 1). Conclusion The developed detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line has good specificity,accuracy and precision with short time consumption(3 h),which can be used as a rapid evaluation method for the biological activity of adalimumab.

Isoimperatorin alleviates acetic acid-induced colitis in rats

@#Objective: To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats. Methods: Colitis was induced by intracolonic administration of acetic acid solution (4% v/v) in rats. Rats were divided into six groups including the sham group, the negative control group, the dexamethasone-treated group, and the groups treated with isoimperatorin (0.1, 1, and 10 mg/kg/d by gavage). The treatments were administered for three days and then colonic status was assessed by macroscopic, histopathological, and biochemical analyses. Results: Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis. It also significantly reduced myeloperoxidase, TNF-α, IL-1β, and malodialdehyde levels. Conclusions: Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

The role of pro-inflammatory cytokines – tumor necrosis factor-alpha and interleukin 6 – in the evolution of diabetic nephropathy: A comparative study

Background: Diabetes is highly prevalent and it is responsible for the increased financial burden on healthcare. Type II diabetes is a more prevalent form of diabetes. Uncontrolled and unsupervised type II diabetes may lead to various microvascular and macrovascular complications which are responsible for high morbidity and mortality. Diabetic nephropathy (DN) is a common complication characterized by the expansion of mesangial cells with thickening of the basement and nodular glomerulosis. TNF-alpha and IL-6 play an important role in causing detrimental changes leading to nephropathy. The study of the role of these inflammatory cytokines in patients with DN may help in the early diagnosis and management. Aims and Objectives: The objectives of this study were to compare the levels of proinflammatory cytokines, TNF-?, and IL-6 in the evolution of DN patients. Materials and Methods: The present study was conducted in the Department of Biochemistry, in collaboration with the Department of Medicine (Nephrology unit); Pt. B.D. Sharma, Post Graduate Institute of Medical Sciences, Rohtak after ethical clearance. Forty patients with DN (Stages 3, 4, and 5) and forty patients with diabetes mellitus without nephropathy were taken up for study after taking informed consent. Results: The mean serum TNF-? levels in cases was 33.05 ± 29.22 pg/mL and in controls was 17.67 ± 12.33 pg/mL. On the basis of unpaired t-test, the difference between the groups was statistically highly significant (P < 0.05). The mean serum interleukin-6 levels in cases was 24.92 ± 30.16 pg/mL (2.95–155.55 pg/mL) and in controls was 6.76 ± 5.82 pg/mL (2.22–35.42 pg/mL). On the basis of the t-test, the difference between the groups was statistically highly significant (P < 0.05). Conclusion: TNF-? and IL-6 may serve as potential biomarkers for patients with DN and also in the development of newer therapeutic modalities for the prevention and treatment of DN.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Correlation between tumor necrosis factor-α and interleukin-1β in exhaled breath condensate and pulmonary function in chronic obstructive pulmonary disease / 中国热带医学

@#Abstract: Objective To explore the correlation between lung function in patients with chronic obstructive pulmonary disease (COPD) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels in exhaled breath condensate (EBC), and to provide a convenient methodological basis for the diagnosis and treatment of COPD and the determination of its efficacy. Methods A total of 81 COPD patients and 40 healthy controls were selected from the respiratory department of the Fourth Affiliated Hospital of Guangzhou Medical University from August 2020 to February 2022 as the research subjects. The COPD patients were divided into 41 cases in the acute exacerbation group and 40 cases in the remission group according to their status. All participants underwent lung function detection, venous blood and EBC collection, and the levels of TNF-α and IL-1β in EBC and venous blood were analyzed by enzyme-linked immunosorbent assay (ELISA), and correlation analysis was performed by Pearson correlation analysis method. Results The levels of TNF-α and IL-1β in EBC of in the acute exacerbation group, the healthy control group, the remission group were (5.16±0.18) pg/μL and (7.75±0.27) pg/μL, (2.66±0.31) pg/μL and (2.41±0.24） pg/μL, (3.61±0.29) pg/μL and (3.17±0.38) pg/μL, respectively. Compared with the healthy control group, the levels of TNF-α and IL-1β in EBC in the COPD acute exacerbation group were significantly higher than those in the healthy control group and the COPD remission group (F=9.451, 8.217, P<0.001). Serum tests were consistent with this result. Correlation analysis showed that the levels of TNF-α and IL-1β in EBC were significantly positively correlated with the level of serum inflammation levels (P<0.001), while significantly negatively correlated with lung function (P<0.001).  Conclusions TNF-α and IL-1β in EBC are potential biomarkers of inflammation in patients with COPD, and their detection can be used to effectively assess lung function in patients with COPD. 

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population

SUMMARY OBJECTIVE: Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. METHODS: The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. RESULTS: A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0.0351 and p=0.032, respectively). CONCLUSION: This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

Evaluation of the efficiency of ciprofloxacin against S. Typhi by altering the production of cytokines in acute typhoid fever in patients at Al-Diwaniyah Hospitals, Iraq

Aims@#Typhoid fever is a life-threatening disease in the developing world that claims >600,000 deaths per year. Its causative agent Salmonella Typhimurium (S. Typhi) can be treated with ciprofloxacin, an effective broad-spectrum antibiotic that enhances the natural host defenses. However, the emergence of resistant bacterial strains may be a warning alarm against the clinical use of this antibiotic. This study was aimed to investigate the efficiency of ciprofloxacin treatment (250 mg/mL) against S. Typhi by altering the production of serum cytokines IL-10, 1L-6 and TNF-α in acute typhoid fever patients in Diwanyah Hospitals.@*Methodology and results@#ELISA and Western Blot methods were used to investigate cytokine levels in patients and healthy controls sera. Our results showed that all cytokines’ levels before treatment with ciprofloxacin were significantly higher than the control (healthy group). However, treated patients with ciprofloxacin revealed a significantly reduced concentration of IL-10 and TNF-α compared to untreated control samples. However, the level of IL-6 was higher even with ciprofloxacin treatment.@*Conclusion, significance and impact of study@#The study concluded that ciprofloxacin (250 mg/mL) might significantly alter serum cytokines IL-6, IL-10 and TNF-α levels in acute typhoid fever patients. Therefore, further molecular studies are essential to understand the effect of ciprofloxacin on the production of cytokines.

Insights into immunopathology and triggering of apoptosis in chronic cerebral toxoplasmosis using murine models

@#Background: toxoplasmosis is a cosmopolitan protozoan disease with a wide range of neuropathology. Recent studies identified its potential association with several mental disorders e.g. schizophrenia dependable on apoptosis in their pathogenesis. We investigated value of toxoplasmosis to induce apoptosis of the neuronal cells. Methods: per-orally infected C57BL/6 mice with 15-20 cysts of the avirulent T. gondii Beverly strain at 9-11 weeks of age were examined 12 weeks later during parasite establishment. Distributions of the parasite’s cysts and the histopathological lesions in the brains were analyzed using Image J software. Relative expression of TNF-α and iNOS of cell-mediated immunity (CMI), Bax (pro-apoptosis) and Bcl-2 (anti-apoptosis) were all assessed using immunohistochemistry. Results: higher parasite burden was seen in the forebrain with p value < 0.05. Dramatically increased TNF-α, iNOS, and Bax expressions with Bax/Bcl-2 ratio 2.42:0.52 were reported (p value < 0.05). The significant correlation between Bax data and different CMI biomarkers including TNF-α and i-NOS was evaluated. Interestingly, no significant correlation was seen between TNF-α, iNOS, Bax and Bcl-2 expressions and location of the parasite. However, Bax/Bcl-2 ratio was statistically correlated with CMI biomarkers and whole sample mean parasite burden, p value < 0.05. Conclusion: Chronic toxoplasmosis exhibits an immense pro-apoptotic signal on the cerebral tissues of experimental mice.

Process in the treatment of non-infectious uveitis with Adalimumab / 国际眼科杂志(Guoji Yanke Zazhi)

@#Uveitis is a clinically common refractory blinding eye disease with complicated etiology and pathogenesis that is difficult to treat and prone to recurrence. It is currently considered to be closely associated autoimmune inflammatory response. Tumor necrosis factor-α(TNF-α)acts as a key pro-inflammatory factor in development and progression of uveitis. Adalimumab(ADA)is a fully humanized recombinant anti-immunoglobulin monoclonal antibody targeting TNF-α, and exerts its biological effects by specifically binding to TNF-α and blocking its binding to tumor necrosis factor receptors(TNFR-1/TNFR-2). This paper reviews the clinical research progress on the mechanism, efficacy and safety of ADA in the treatment of non-infectious uveitis.

Changes and clinical significance of four biomarkers in gingival crevicular fluid after nonsurgical periodontal therapy / 口腔疾病防治

Objective@# To study the changes in levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and alkaline phosphatase (ALP) in the gingival crevicular fluid (GCF) of patients with severe chronic periodontitis before and after nonsurgical periodontal therapy and to explore the relationship among the levels of these four biomarkers in GCF, their periodontal status and their clinical significance to evaluate the effect of nonsurgical periodontal therapy and periodontitis activity.@*Methods@# In total, 30 patients with severe chronic periodontitis were enrolled in a 1-year longitudinal pilot study (Chinese Clinical Trial Registry: ChiCTR-OCH-13004679). At baseline and 1, 3, 6, and 12 months after nonsurgical therapy, the periodontal clinical indicators plaque index (PLI), probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI) were recorded. Filter paper strips were used to collect two deep-pocket (probing depth ≥ 6 mm) and two shallow-pocket (probing depth ≤ 4 mm) periodontal sites for each patient and weighed. The levels of interleukin IL-6, IL-10, TNF-α, and ALP in GCF were assessed using enzyme-linked immunosorbent assay. Meanwhile, 30 healthy sites of 15 subjects with healthy periodontium were used as the baseline controls for patients with severe chronic periodontitis.@*Results @#At the baseline, the TNF-α, ALP and IL-6 levels in GCF of the disease sites of patients with periodontitis were significantly higher than those in healthy periodontal sites of the control group (P < 0.001), and the levels of IL-10 were significantly lower than those in the control group (P < 0.001). In patients with severe chronic periodontitis, the levels of TNF-α, ALP and IL-6 in GCF at deep-pocket sites were significantly higher than those at shallow-pocket sites (P <0.001), and the IL-10 levels were significantly lower than those at shallow-pocket sites (P < 0.001). 1, 3, 6, and 12 months after nonsurgical treatment, the levels of TNF-α and ALP in GCF at the shallow- and deep-pocket sites in patients with chronic periodontitis significantly decreased, the level of IL-10 significantly increased (P < 0.005), and the level of IL-6 in GCF at the deep-pocket sites significantly decreased (P < 0.005). However, there was no significant difference in IL-6 level at shallow-pocket sites (P > 0.05). 1, 3, 6, and 12 months after nonsurgical treatment, the periodontal clinical indicators were improved compared with the baseline. In addition, there was a significant correlation between the levels of these four biomarkers and the periodontal clinical parameters (P < 0.05). During the two follow-up visits after nonsurgical periodontal therapy, the sites with more than 2-mm increase in attachment loss had significant differences in the levels of the four biomarkers in the GCF compared with the previous visit time (P < 0.005).@*Conclusion@#The detection of the levels of these four biomarkers in GCF has strong clinical significance for assessing the severity of periodontitis and the efficacy of nonsurgical periodontal therapy. Increased levels of TNF-α, ALP, and IL-6 and decreased IL-10 levels in GCF may indicate periodontitis progression at this site.

Inhibition of Activin A suppressed tumor necrosis factor-α secretion and improved histopathological conditions in malarial mice

@#Malaria infection still remains as one of the most prominent parasitic diseases afflicting mankind in tropical and subtropical regions. The severity of malaria infection has often been associated to exuberant host immune inflammatory responses that could possibly lead to severe immunopathological conditions and subsequent death of host tissues. Activin A is a protein belonging to the transforming growth factor-beta (TGF-β) family that regulates multiple physiological processes and pathological-associated diseases. The biological roles of activin A have been associated with manipulation of inflammation-related processes and modulation of host immune responses. This implies that activin A protein could play a role in malaria pathogenesis since malaria infection has been closely linked to severe immune responses leading to death, However, the actual in vivo role of activin A in malaria infection remains elusive. Hence, this study was undertaken to investigate the involvement of activin A in malaria infection as well as to assess the modulating effects of activin A on the cytokine releases (TNF-α, IFN-γ and IL-10) and histopathological changes in major affected organs (kidney, liver, lung, brain and spleen) in malarial mice infected with Plasmodium berghei ANKA. Our results showed that the concentrations of plasma activin A were significantly increased in malarial mice throughout the study periods. Also. the systemic activin A level was positively correlated with malaria parasitemia. This indicates that activin A could play a role in malaria pathogenesis and malaria parasitemia development. Plasma TNF-α, IFN-γ and IL-10 cytokine levels were significantly increased in malarial mice at day-5 post infection, suggesting that these cytokines attributed to severe malaria pathogenesis. Histopathological features such as sequestration of parasitized red blood cells (pRBCs) and hemozoin formation were amongst the most common pathological conditions observed in tissues of major affected organs (kidney, liver, lung, brain and spleen) in malarial mice. Neutralization of activin A production via recombinant mouse activin RIIA Fc chimera (rmActivin RIIA Fc chimera) had significantly reduced the parasitemia levels in malarial mice. The release of TNF-α cytokine was significantly reduced as well as the sequestration of parasitized pRBCs and hemozoin formation in major affected organs in malarial mice were also alleviated following inhibition of activin A production. Overall, this preliminary study suggests that activin A could play an immune modulation role in malaria pathogenesis through modulation of TNF-α release that benefits host from severe pathological destructions provoked by intensified inflammatory responses. Further studies are warranted to elucidate the precise mechanism of immune modulation mediated by activin A and its associated immune-modulation mediators in regulating the inflammatory responses elicited during the course of malaria infection.

Establishment of rabbit dry eye cells model and evaluation of its biological characteristics / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To further explore effective drugs for dry eye treatment by isolating and culturing lacrimal gland epithelial cells<i> in vitro</i>, establishing a dry eye cell model and analyzing relevant inflammatory factors. <p>METHODS: Rabbit lacrimal gland epithelial cells were <i>in vitro</i> isolated and cultured, and the activity and purity of primary cells were identified by cell proliferation experiment and immunofluorescence experiment. In addition, 0.5 times IC₅₀ of lipopolysaccharide LPS and TNF-α were used respectively to stimulate rabbit lacrimal gland epithelial cells and then establish two dry eye cell models. Finally, through cell proliferation experiment, ELISA and flow cytometry, the biological characteristics of these two dry eye cell models were compared. <p>RESULTS:After 12h of culture, the primary cells of lacrimal gland epithelial cells basically adhered to the wall of culture bottles; and 48h later, the cells stretched and almost each of them presented a shape of a long triangle. The activity of primary cells of lacrimal gland epithelium was 92%, and the positive rate of marker Pan-rkeratin was more than 90%, which accorded with the experimental requirements. The IC₅₀ of LPS and TNF-α are 20μg/mL and 4.996ng/mL respectively. After 12h of intervention with LPS(10μg/mL)and TNF-α(2.5ng/mL), the cell activity of the two groups was significantly lower than that of control group(<i>P</i><0.01); compared between these two groups, the apoptosis rate of TNF-α group is higher than that of LPS group(<i>P</i><0.01). The levers of IL-1β and IL-6 in the cell supernatants of the two groups were significantly higher than those of the control group(<i>P</i><0.01); compared between the two groups, IL-1β and IL-6 in TNF-α group were significantly higher than those in LPS group(<i>P</i><0.01). It was suggested that TNF-α was superior to LPS in simulating inflammatory response of dry eye. <p>CONCLUSION: This study successfully established a relatively simple and rapid rabbit dry eye cell model with high cell purity and stability, which provided a more stable <i>in vitro</i> experimental model for the basic research on the function of rabbit lacrimal gland epithelial cells and dry eye.

Effect of TNF-α/IL-10 imbalance caused by cerebral embolism in middle-aged and elderly patients on neuronal damage and pain / 中风与神经疾病杂志

@#Objective　To explore the effect of TNF-α/IL-10 imbalance caused by cerebral embolism in middle-aged and elderly patients on neuronal damage and pain.Methods　The middle-aged and elderly patients with cerebral embolism and non-cerebral infarction who were treated in our hospital from April 2018 to August 2020 were selected as research objects.The blood of these patients was collected and analyzed by ELISA method.TNF-α and IL-10 in the cerebrospinal fluid of the two groups of subjects were measured to evaluate the neurological function and pain degree of the patients.Results　In middle-aged and elderly patients with cerebral embolism type cerebral infarction,the abnormal secretion of TNF-α was caused by the apoptosis of neuronal cells.Glial cells and vascular endothelial cells contribute to the imbalance of TNF-α/IL-10 ratio and the patient’s inflammatory response and pain.Therefore,the imbalance of TNF-α/IL-10 ratio will dynamically change in the cerebrospinal fluid of middle-aged and elderly patients with cerebral embolism cerebral infarction,which can be used to evaluate the patient’s condition and has clinical value.Conclusion　TNF-α in middle-aged and elderly patients with cerebral embolism cerebral infarction-α and AQP-4 abnormal secretion,TNF-α/the ratio of IL-10 was unbalanced;these indicators can be used to evaluate the degree of the patient’s condition,with clinical value.

Emodin ameliorates diabetic neuropathic pain through inhibiting up-regulation of TRPV1 and pro-inflammatory cytokines in dorsal root ganglions in rats

@#Background & Objective: Peripheral neuropathy is one of the most common complications of diabetes and leads to sensory symptoms, including diabetic neuropathic pain (DNP). Emodin has potential analgesic effect for the treatment of pain-related diseases. However, the analgesic effect of emodin on DNP and its possible mechanism remains unknown. The aim of the present study is to investigate the effect of emodin on STZ-induced DNP in rats and its potential molecular mechanism. Methods: To determine the analgesic effect of emodin on DNP, a mouse model of STZ-induced DNP was established. The pain-related behaviors were evaluated by von Frey test, and hot plate test. The mRNA and protein expression of several TRP channels was detected by qRT-PCR and western blot methods, and the level of inflammatory cytokines was determined by ELISA. Results: The mechanical and thermal pain thresholds were significantly decreased in DNP rats. A single injection of emodin treatment significantly reduced DNP. Further results demonstrated that emodin inhibited the up-regulation of Trpv1 mRNA in the DRG of DNP rats. Our data also indicated that emodin significantly reduced the levels of TNF-α, IL-1β and IL-6 in the DRG of DNP rats. Conclusions: Emodin ameliorates mechanical allodynia and thermal hyperalgesia in DNP rats by down-regulating the expression of TRPV1 in DRG and the expression of TNF-α, IL-1β and IL-6. Emodin serves as a potent analgesic reagent for treatment and prevention of DNP.

Short-term treatment efficacy of NK cells for ovarian cancer ascites / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the short-term clinical efficacy and safety of intraperitoneal perfusion of natural killer (NK) cells in the treatment of ovarian cancer with ascites. Methods: The clinical data of 15 ovarian cancer patients with ascites effusion, who received NK cell perfusion in the Qinhuai Medical District of the General Hospital of Eastern Theater Command from November 2016 to January 2019, were analyzed. The peripheral blood was collected to isolate the peripheral blood mononuclear cells, and to further obtain the NK cells after culture. NK cell suspension was intraperitoneally perfused into the abdominal cavity (no less than 2×109 cells/ time). The volume of peritoneal effusion, the level of serum tumor marker CA-125, the level of serum cytokines IL-2, INF-γ and TNF-α as well as the changes in peripheral blood lymphocyte subsets were detected before and after the treatment; Moreover, the clinical efficacy and adverse reactions were observed. Results: The effective rate of intraperitoneal perfusion of NK cells was 66.7%, and there were no obvious treatment-related adverse reactions. Compared with before treatment, the serum tumor marker CA-125 level significantly decreased after treatment (P<0.05), and the levels of IL-15, IFN-γ and TNF-α increased significantly (P<0.05 or P<0.01), while there was no significant changes in peripheral blood lymphocyte subsets (all P>0.05). Conclusion: Intraperitoneal infusion of NK cells in the treatment of ovarian cancer associated peritoneal effusion has a good short-term clinical efficacy with little adverse reactions, which is a promising method for the treatment of cancerous peritoneal effusion.

The effect of musk on cerebral ischemia-reperfusion in rats / Монголын Анагаах Ухаан

Introduction @#In recent years, there has been a significant increase of cerebrovascular disease in Mongolia, which is the second leading cause of mortality. There are dozens of Mongolian traditional medicine which is good efficiency for cerebral ischemia that contains musk.@*Aim@#Therefore, we aimed to investigate the effect of musk under the cerebral ischemia/reperfusion in rats.@*Materials and Methods@#Cerebral middle cerebral artery occlusion was established in male rat (90-minute occlusion followed by 24-hour reperfusion). Rats were divided into following groups: control group, ischemia group (cerebral ischemia and reperfusion), nimodipine administrated group (cerebral ischemia and reperfusion + treated with nimodipine), musk administrated group (cerebral ischemia and reperfusion + musk 50 mg/kg and 100 mg/kg). The brain tissue levels of IL-1β, TNF-α, IL-6, IL-10 cytokines were measured using enzyme linked immunosorbent assay (ELISA) every 1, 3, 7th days.@*Results@#Levels of cytokines (IL-1β, TNF-α and IL-6) were significantly lower in musk treated group compared to brain ischemia group (p<0.05). In contrast, treatment with musk was significantly improved neurological function with stimulation of M2 phenotype microglia cells and increased the anti-inflammatory cytokine level of IL-10 in the ischemic hemisphere of brain in rats@*Conclusion@#The mechanisms of musk are associated with increasing the brain tissue levels of IL-10, and reducing the levels of proinflammatory cytokines such as IL-1β, TNF-α, IL-6 subsequently stimulating neurogenesis and reduced ischemic zone. Musk may have neuroprotective effects against cerebral ischemia with stimulating M2 phenotype microglia cells in the brain. Regarding the ELISA, the effects of musk may be due to anti-inflammatory properties through inhibition of some of proinflammatory cytokines and stimulation of anti- inflammatory cytokines.

Mechanism of Apolipoprotein E affecting the expression of Matrix Metalloproteinase-9 Astrocytes / 中风与神经疾病杂志

@#Objective　To explore the mechanism of apolipoprotein E （ApoE） affecting the expression of matrix metalloproteinase-9 （MMP-9） in astrocytes. Methods　（1） Astrocytes in wild-type （WT） and ApoE gene knockout （ApoE-/-） C57BL / 6J suckling mice were cultured in vitro；glial fibrillary acidic protein （GFAP） antibody were employed to identified the astrocytes. （2） Astrocytes from wild type WT and ApoE-/- C57BL/6J suckling mice were divided into blank control group（Control group），negative control group（NC group） and p65 gene knock down group（KD group）. No lentivirus was added to the Control group. The negative control lentivirus was added to the NC group，and the positive lentivirus that silended the p65 gene was added to the KD group. The nuclear factor-κB （NF-κB） p65 gene of astrocytes was silenced with siRNA lentivirus to inhibit NF-κB signal transduction. The expression of p65 protein was detected by Western blot，and MMP-9 and tumor necrosis factor-α（TNF-α） were detected by ELISA. （3）Add TNF-α to stimulate the astrocytes of each group for 24 hours，and the concentration of MMP-9 in each group of astrocytes before and after stimulation was measured by ELISA. Results　（1） The expression of NF-κB p65 protein and the concentrations of MMP-9 and TNF-α in the two astrocytes in the KD group were significantly lower than those in the Control group and the NC group （P<0.05），but those between the Control group and the NC group were no significant different（P>0.05）；（2） The concentration of MMP-9 and TNF-α of ApoE-/- astrocytes were higher than WT astrocytes in the Control group and NC groups （P<0.05），while those was no significant difference between ApoE-/- astrocytes and WT astrocytes in KD group （P>0.05）；（3） The concentrations of MMP-9 of the two types of astrocytes in Control group and NC group was increased after the stimulation of TNF-α（P<0.05），while the concentration of MMP-9 in the KD group had no significant change（P>0.05）. Conclusion　ApoE may affect the expression of MMP-9 in astrocytes through the TNF-α/NF-κB signaling pathway，and then affects the integrity of the blood-brain barrier.

The mechanism of omega-3 unsaturated fatty acid DHA on β-amyloid-induced memory impairment in mice / 中风与神经疾病杂志

@#Objective　To analyze the effects of omega-3 unsaturated fatty acid DHA on memory in mice model with Alzheimer’s disease (AD).Methods　 Thirty-six mice were randomly divided into sham operation group (sodium carboxymethyl cellulose gavage),Aβ model group (sodium carboxymethyl cellulose gavage) and Aβ+DHA group (DHA gavage).AD mice model were established by injecting oligomeric Aβ1-42 into the hippocampus of 36 mice by Aβ-intrahippocampal injection method.The memory function of mice were observed by Morris water maze test and the changes in hippocampal neurons of AD rats were determined by Nissl’s staining;In the hippocampus,the content of TNF-α and IL-16 were measured by ELISA and the expression of BDNF,IFN-γ and NF-κB protein were detected by Western blot.Results　Compared with sham operation group,prolongation of latency prolonged,the number of crossing platform and the expression of BDNF protein decreased,while TNF-α content,IL-16 content,IFN-γ protein expression and NF-κB protein expression increased in Aβ model group and Aβ+DHA group.Compared with the Aβ model group,the latency shortened,the number of crossing platform and BDNF protein expression increased,while the TNF-α content,IL-16 content,IFN-γ protein expression and NF-κB protein expression decreased in Aβ+DHA group,the differences were all statistically significant (P<0.05).Conclusion　DHA can improve memory impairment in AD mice induced by Aβ1-42,and its mechanism may be related to decreasing the content of TNF-α and IL-16,inhibiting the expression of IFN-γ and NF-κB,and promoting the expression of BDNF protein in hippocampus.

The significance of CD4+CD28-T cells，TNF-α and VCAM-1 in acute cerebral infarction and its correlation with the properties of carotid plaque / 中风与神经疾病杂志

@#Objective　To investigate the changes of CD4+CD28-T lymphocytes subsets，tumor necrosis factor-α（TNF-α） and vascular cell adhesion molecule-1（VCAM-1） in peripheral blood of patients with acute cerebral infarction（ACI） and their correlation with the nature of carotid plaques. Further analysis of the correlation among CD4+CD28-T cells，TNF-α and VCAM-1 in patients with cerebral infarction. Methods　From August 2018 to April 2019，CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in peripheral blood of 57 patients with acute atherosclerotic cerebral infarction,43 patients with acute arterioarterial cerebral infarction and 40 healthy controls were collected and were detected by flow cytometry and ELISA in the Department of Neurology,the Affilated of Shengjing Hospital of China Medical University,and the level of CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in different groups was analyzed. 47 patients with internal carotid artery plaques were obtained by carotid color Doppler ultrasound in 57 patients with acute atherosclerotic cerebral infarction，including 19 patients with stable plaques and 28 patients with unstable plaques. The relationship between CD4+CD28-T lymphocytes，TNF-α，VCAM-1 and atherosclerotic cerebral infarction plaque stability was analyzed. The correlation between them in patients with acute cerebral infarction was determined by scatter plot. Results　The levels of CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in peripheral blood of patients with acute atherosclerotic cerebral infarction were higher than those of patients with arteriole cerebral infarction，and the levels of CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in both groups was higher than those in healthy controls，and there were significant difference among three groups（P<0.05）. The levels of CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in unstable plaque group were higher that in stable plaque group.There was significant difference between the two groups（P<0.05）.At the same time，there was a linear correlation between CD4+CD28-T lymphocytes and TNF-α，VCAM-1 in all patients with acute cerebral infarction. Conclusion　The levels of CD4+CD28-T lymphocytes，TNF-α and VCAM-1 in peripheral blood of patients with acute cerebral infarction during the acute phage were increased，and CD4+CD28-T lymphocytes，TNF-α and VCAM-1 were mainly involved in the formation of atherosclerotic unstable plaques. The levels of CD4+CD28-T lymphocytes were correlated with TNF-α and VCAM-1 in patients with acute cerebral infarction，respectively.