Nitric oxide and tumor necrosis factor-⍺ levels are negatively correlated in endotoxin tolerance recovery in vitro.

Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS1, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS2, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS1 treatment with or without the iNOS-specific inhibitor, 1400W. LPS2-induced tumor necrosis factor-⍺ (TNF-⍺) and interleukin-6 (IL-6) were downregulated after LPS1 treatment, confirming the development of ET. Notably, TNF-⍺ and IL-6 levels spontaneously rebounded after 12-24 h of resting following LPS1 treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.

Anti-inflammatory effects of probiotics and synbiotics on patients with non-alcoholic fatty liver disease: An umbrella study on meta-analyses.

BACKGROUND AND AIM: The impact of chronic low-grade inflammation in the development of non-alcoholic fatty liver disease (NAFLD) has been studied widely. Previous studies showed gut pathogens' effects on inflammation development in NAFLD patients; hence, hypothetically, gut microbial therapy by administration of probiotics, synbiotics, and prebiotics may alleviate inflammation in these individuals. Several studies were performed in this regard; however, conflicting results were obtained. In this study, we aimed to comprehensively evaluate the effects of gut microbial therapy on inflammatory markers in NAFLD patients in a meta-umbrella design. METHODS: Two independent researchers investigated international databases, including PubMed, Web of Science, Scopus, and Cochrane Library, from inception until March 2023. Meta-analyses evaluating the impact of probiotics, synbiotics, or prebiotics on inflammatory markers of patients with NAFLD were eligible for our study. AMASTAR 2 checklist was used to evaluate the quality of included studies. Random effect model was performed for the analysis, and Egger's regression test was conducted to determine publication bias. RESULTS: A total number of 12 studies were entered into our analysis. Our findings revealed that gut microbial therapy could significantly reduce serum C-reactive protein (CRP) levels among NAFLD patients (ES: -0.58; 95% CI: -0.73, -0.44, P < 0.001). In subgroup analysis, this reduction was observed with both probiotics (ES: -0.63; 95% CI: -0.81, -0.45, P < 0.001) and synbiotics (ES: -0.49; 95% CI: -0.74, -0.24, P < 0.001). In addition, gut microbial therapy could significantly decrease tumor necrosis factor-a (TNF-a) levels in NAFLD patients (ES: -0.48; 95% CI: -0.67 to -0.30, P < 0.001). In subgroup analysis, this decrease was observed with probiotics (ES: -0.32; 95% CI: -0.53, -0.11, P = 0.002) and synbiotics (ES: -0.96; 95% CI: -1.32, -0.60, P < 0.001). Not enough information was available for assessing prebiotics' impacts. CONCLUSION: The results of this umbrella review suggest that probiotics and synbiotics have promising effects on inflammatory markers, including TNF-a and CRP; however, more research is needed regarding the effects of prebiotics. PROSPERO REGISTRATION CODE: CRD42022346998.

Dynamic thiol-disulfide homeostasis as an oxidative stress marker in ankylosing spondylitis and undifferentiated spondyloarthropathy.

Background/aim: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of rheumatologic diseases, including SpA. This prospective case-control study was designed to compare thiol-disulfide levels as a marker of oxidative stress between SpA patients and healthy controls. Materials and methods: A total of 144 patients diagnosed with undifferentiated spondyloarthropathy (USpA, n = 97) or ankylosing spondylitis (AS, n = 47) were included along with 80 healthy controls. Serum native thiol (NT), total thiol (TT), and disulfide (D) levels were measured using the fully automated Erel method. The ratios NT/TT, D/TT, and D/NT were calculated. Thiol-disulfide levels were compared between the SpA groups and the healthy controls. Results: The NT and NT/TT ratios were found to be significantly lower in the SpA group (p < 0.001). The disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p < 0.001). In pairwise comparisons between the SpA subgroups, the NT and TT levels were lower in the USpA group than in the AS group (p = 0.021), but serum disulfide levels were higher in the USpA group than in the AS group (p = 0.004). Among the patients with SpA, the group taking antitumor necrosis factor (anti-TNF) had lower TT measurements compared to the group taking conventional disease modifying antirheumatic drugs (DMARD) (p = 0.039). Conclusion: The thiol-disulfide balance is disturbed in favor of disulfide in SpA patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the conventional DMARD in SpA patients.

Microbiome-Based Hypothesis on Ivermectin's Mechanism in COVID-19: Ivermectin Feeds Bifidobacteria to Boost Immunity.

Ivermectin is an anti-parasitic agent that has gained attention as a potential COVID-19 therapeutic. It is a compound of the type Avermectin, which is a fermented by-product of Streptomyces avermitilis. Bifidobacterium is a member of the same phylum as Streptomyces spp., suggesting it may have a symbiotic relation with Streptomyces. Decreased Bifidobacterium levels are observed in COVID-19 susceptibility states, including old age, autoimmune disorder, and obesity. We hypothesize that Ivermectin, as a by-product of Streptomyces fermentation, is capable of feeding Bifidobacterium, thereby possibly preventing against COVID-19 susceptibilities. Moreover, Bifidobacterium may be capable of boosting natural immunity, offering more direct COVID-19 protection. These data concord with our study, as well as others, that show Ivermectin protects against COVID-19.

Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations.

Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti-CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8+ T cell activation and upregulation of IFNγ, TNFα and IL-1ß signaling. The effective anti-tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8+ T cells but was unaffected when TNFα or IL-1ß cytokine signaling pathways were blocked. Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.

Therapeutic effects of Guchisan combined with orthodontics therapy on chronic periodontitis with syndrome of excessive stomach fire in 33 patients / 中国基层医药

Objective:To investigate the effects of Guchisan combined with orthodontics therapy on serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Methods:Sixty-six patients with chronic periodontitis who received treatment in Zhejiang Xin'an International Hospital between July 2013 and July 2019 were included in this study. They were randomly divided into control group ( n = 33) and treatment group ( n = 33). Both control and treatment groups received conventional interventions. The control group was treated with orthodontics therapy. The treatment group was treated with Guchisan (0.5 g once, twice a day, 2-3 minutes once) based on orthodontics therapy for 1 month. Gingival index, probing depth, attachment loss, plaque index, gingival bleeding index, and latency to symptom improvement were compared between the two groups. Clinical efficacy was compared between the two groups. Serum IL-1β and TNF-α levels were measured in each group. Results:After treatment, gingival index [(0.51 ± 0.06) vs. (1.12 ± 0.15), t = 21.69], probing depth [(2.01 ± 0.22) mm vs. (2.67 ± 0.30) mm, t = 6.50], attachment loss [(1.10 ± 0.13) mm vs. (1.70 ± 0.18) mm, t = 9.90], plaque index [(0.47 ± 0.05) vs. (1.08 ± 0.13), t = 25.57], and gingival bleeding index [(0.58 ± 0.07) vs. (1.09 ± 0.13), t = 19.84] were significantly lower than those in the control group (all P < 0.01). Latency to tooth loosening [(8.81 ± 0.96) days vs. (13.03 ± 1.62) days, t = 15.01], halitosis [(3.04 ± 0.33) days vs. (7.03 ± 0.76) days, t = 27.66], and swollen gums [(2.21 ± 0.24) days vs. (4.55 ± 0.51) days, t = 23.85] were significantly shorter than those in the control group (all P < 0.01). Total response rate in the treatment group was significantly higher than that in the control group (93.94% vs. 69.70%, χ2 = 4.99, P = 0.025). After treatment, serum levels of TNF-α [(4.01 ± 0.44) ng/L vs. (5.31 ± 0.58) ng/L, t = 10.26] and IL-1β [(16.04 ± 1.97) mg/L vs. (18.30 ± 2.55) mg/L, t = 4.03] in the treatment group were significantly lower than those in the control group (both P < 0.01). Conclusion:Based on conventional treatment, Guchisan combined with orthodontics therapy for treatment of chronic periodontitis with syndrome of excessive stomach fire can greatly improve symptoms of periodontal disease and enhance clinical efficacy. Lowering serum TNF-α and IL-1β levels may be one of effective action ways of this combined therapy.

Intervention of total saponins of Panax japonicas on non-alcoholic steatohepatitis in mice by regulating miR-199/SIRTl/MFN2 / 中国药理学通报

Aim To discuss the effect of miR-199/ SIRT1/MFN2 signaling pathway on the progression of NASH and its related mechanisms.Methods 45 BALB/e mice were randomly divided into normal group, high fat diet(HFD) group, total saponins of panax japonicas ( TSPJ ) low-dose group ( 15 mg • kg-1) and TSPJ high-dose group (45 mg • kg"1 ).Normal group was given normal diet, while HFD group, TSPJ low-dose and high-dose groups were given high-fat diet.The mice were intragastrioally given 15 and 45 mg 'kg"1 TSPJ (dissolved in saline) daily in TSPJ low-dose and high-dose groups, while those in other groups were intragastric ally given the same a- mount of saline daily.After seven months, they were sacrificed for serum collection and hepatic tissue col¬lection.Results HE staining showed that liver lipido¬sis and inflammation were obvious in HFD group.while liver lipidosis anrl inflammation were alleviated in TSPJ group.MFN2 and SIRT1 levels significantly de¬creased.TNF-a, 1L-1 p , SREBP, ChREBP levels sig¬nificantly increased in HFD group.After treated with TSPJ, SIRT1 and MFN2 levels were significantly up- regulated , while TNF-a, IL-ip, ChREBP and SREBP levels were significantly down-regulated.The Immuno¬fluorescence results showed that the fluorescence inten¬sity of MFN2 and SIR 11 increased in TSPJ low-dose and high-dose groups.At mRNA level, miR-199 had a negative regulatory relationship with SIRT1.Conclu¬sions TSPJ can alleviate NASH induced by high fat diet through miR-199/SIRTl/MFN2 signaling path¬way.

Systematic review and meta-analysis: real-world data rates of deep remission with anti-TNFα in inflammatory bowel disease.

BACKGROUND: Deep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, real-world data (RWD) can provide information complementary to RCTs, specifically regarding treatment duration. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα. METHODS: We completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012 to 2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years. Risk of bias was assessed with the Newcastle Ottawa Scale. RESULTS: 29,033 publications were identified. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1212 patients (769 Crohn's disease-CD, 443 ulcerative colitis-UC), and analyzed using Comprehensive Meta-Analysis. Rate of DR was 36.4% (95% CI 12.6-69.4%) at 8 weeks, 39.1% (95% CI 10.4-78%) at 6 months, 44.4% (95% CI 34.6-54.6%) at 1 year, and 36% (95% CI 18.7-58%) at 2 years. DR in CD at 1 year was 48.6% (95% CI 32.8-64.7%) and in UC was 43.6% (95% CI 32.8-55.1%). CONCLUSIONS: The rate of DR was highest after 1 year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.

Shashen maidong decoction: the effect of TNF-α and IL-6 on lung cancer cachexia based on cancer toxicity theory.

OBJECTIVE: To study the curative effect of the traditional Chinese medicine (TCM) Shashen Maidong Decoction in treating lung cancer cachexia based on the cancer toxicity theory, and analyze its influence on patients' serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). METHODS: From January 2018 to January 2019, 104 patients with primary lung cancer cachexia diagnosed and treated in our hospital's oncology department were selected and randomly divided into experimental group and control group, with 52 cases in each group. The control group received routine treatment and nutritional support, while the experimental group received Shashen Maidong Decoction plus. Indexes were compared and analyzed before and after 4 weeks of treatment, including TCM syndrome score, Patient-Generated Subjective Global Assessment (PG-SGA) score, Karnofsky score (KPS), albumin, prealbumin, TNF-α and IL-6 levels. RESULTS: (1) After treatment, both groups' PG-SGA score, KPS score and TCM syndrome score were better than those before treatment (P < 0.01), and the experimental group's PG-SGA score, KPS score and TCM syndrome score were higher than those of the control group (P < 0.01). (2) After treatment, both groups' serum albumin and prealbumin levels were higher than those before treatment (P < 0.05), and the experimental group's prealbumin level was higher than that in the control group (P < 0.05). (3) After treatment, both groups' serum levels of TNF-α and IL-6 were lower than those before treatment (P < 0.05), and the experimental group's levels of TNF-α and IL-6 were lower than those in the control group (P < 0.05). CONCLUSION: Based on the cancer toxicity theory, the application of Shashen Maidong Decoction in treating lung cancer cachexia has definite therapeutic effects and important clinical values. It can effectively alleviate patients' symptoms, improve nutritional status, and reduce body's inflammatory response.

Immune responses to injury and their links to eye disease.

The eye is regarded as an immune privileged site. Since the presence of a vasculature would impair vision, the vasculature of the eye is located outside of the central light path. As a result, many regions of the eye evolved mechanisms to deliver immune cells to sites of dysgenesis, injury, or in response to the many age-related pathologies. While the purpose of these immune responses is reparative or protective, cytokines released by immune cells compromise visual acuity by inducing inflammation and fibrosis. The response to traumatic or pathological injury is distinct in different regions of the eye. Age-related diseases impact both the anterior and posterior segment and lead to reduced quality of life and blindness. Here we focus attention on the role that inflammation and fibrosis play in the progression of age-related pathologies of the cornea and the lens as well as in glaucoma, the formation of epiretinal membranes, and in proliferative vitreoretinopathy.

Dynamic Thiol/Disulphide Homeostasis as Oxidative Stress Marker in Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy.

AIM: Seronegative spondyloarthropathies (SpA) are a group of chronic diseases, characterized by axial inflammation, oligoarthritis, and enthesitis. Oxidative stress may contribute to a wide range of diseases such as rheumatologic diseases including SpA. This prospective case-control study was designed to compare the thiol-disulfide levels as a marker of oxidative stress in SpA patients with healthy controls. METHODS: A total of 144 patients who were diagnosed as undifferentiated spondyloarthropathy (UspA, n=97), ankylosing spondylitis (AS, n=47), and 80 healthy controls were included. Serum native thiol (NT), total thiol (TT), disulfide (D) levels were measured with the fully automated Erel?s method. NT/TT, D/TT, and D/NT ratios were calculated. Thiol-disulfide levels were compared between SpA groups and healthy controls. RESULTS: NT and NT/TT ratios were found to be significantly lower in the SpA group. (p<0.001). Disulfide, D/NT, and D/TT ratios were found to be significantly higher in the SpA group (p <0.001 for each comparison). In pairwise comparisons between SpA subgroups, NT and TT levels were lower in USpA group compared to AS group (P=0.021). Serum disulfide levels were higher in USpA group compared to AS group (P=0,004). Anti-tumor necrosis factor (Anti-TNF) group had lower TT measurements compared to the classical disease-modifying anti-rheumatic drugs (cDMARD) group in patients with SpA (P=0.039). CONCLUSION: Thiol-disulfide balance is disturbed in favor of disulfide in SpAs patients compared to healthy volunteers. Native and total thiol measurements correlate with acute phase reactants and might be used to monitor disease activity. Anti-TNF therapy might control the oxidative degenerative process better than the classical DMARD in SpA patients.

Infliximab therapy in an infant with Netherton syndrome.

We present a patient with Netherton syndrome and severe skin manifestations treated with infliximab. By 6 months of age, the child had intractable pruritus, scaling, dry skin, and generalized eczematous lesions resistant to conventional therapies for atopic dermatitis. Clinical improvement was observed following the third infusion of infliximab, and by 12 months of age, the skin lesions completely resolved. Infliximab is a promising option for the management of skin inflammation in Netherton syndrome, even in infants.

The effects of the phytochemistry of cocoa on the food chemistry of chocolate(s) and how disease resistance in cocoa can be improved using CRISPR/Cas9 technology.

Consumers' rating of "chocolate brands" are majorly based on texture and taste rather than packaging. The texture/taste of a chocolate bar is largely influenced by the cocoa variety used for its production, whereas, its bioactive constituent is directly affected by the seed processing/chocolate manufacturing technique(s) adopted, and the additives used. Cacao is the key ingredient for chocolate production; therefore, the choicest varieties must be used to protect consumers' interest. Currently, the availability of the African variety is the only reason why it is globally sought-after for chocolate production rather than its taste. Therefore, a transfer of genetic materials from quality cocoa breeds into the high-yielding and resilient African variety or vice versa, would inferably increase the availability of quality cocoa beans all-year-round, and also increase the chances of obtaining sumptuous and palatable chocolates anywhere in the world.

Aucubin protects cardiomyocytes from apoptosis by activating ERß pathway / 中国药理学通报

Aim To explore the effect of aucubin aucubin (AU), one of the effective ingredients of eucommia, plantain, rehmannia and other herbs, on cardiomyocyte apoptosis and cardiac function after acute myocardial infarction (MI) and the possible mechanisms. Methods In this study, the mouse models of MI were established by ligation of the anterior descending branch of the left coronary artery. Left ventricular function and the infarct size were detected using echocardiography and Masson staining. A Tumor necrosis factor-a (TNF-ot)/cycloheximide (C H X) model of cardiomyocyte injury was established, and the effects AU on myocardial injury were examined using IncuCyte live cell imaging, Western blot and TUNEL staining. Results AU administration dramatically improved cardiac function recovery and decreased infarct size after MI. AU inhibited the apoptosis of cardiomyocytes, reduced the expressions of caspase-3, and significantly increased the ratio of Bcl-2/Bax induced by TNF-ot/ CHX. Meanwhile, the estrogen receptor ß (ERß) protein level was elevated by AU, and the antiapoptotic effect of AU was blocked by ERß inhibitor. Conclusions AU can alleviate MI injury and improve cardiac function via inhibiting the apoptosis of cardiomyocytes, and its mechanism is the activation of ERß pathway.

Clinical effect of Changweishu on gastrointestinal dysfunction in patients with sepsis.

OBJECTIVE: To investigate Changweishu's clinical effect on gastrointestinal dysfunction in patients with sepsis. METHODS: Fifty patients with gastrointestinal dysfunction and sepsis were randomly divided into treatment and control groups. The control group patients received routine Western medicine treatments (meropenem, noradrenaline, glutamine glue, Bifidobacterium lactis triple-strain tablet), and the treatment group patients received routine Western medicine treatment combined with Changweishu. Treatments in both groups lasted 7 days. Changes in APACHE II score, gastrointestinal dysfunction score, serum levels of diamine oxidase (DAO), D-lactic acid, inflammatory factors (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB-1)), and the incidence of multiple organ dysfunction syndrome (MODS) and mortality were observed. RESULTS: After treatment, APACHE II score, gastrointestinal dysfunction score, and DAO, D-lactic acid, TNF-α, IL-6, and HMGB-1 levels decreased significantly in both groups, but the decrease was more significant in the treatment group than in the control group. The incidence of MODS and mortality were significantly lower in the treatment group than in the control group. CONCLUSION: The addition of Changweishu to routine Western treatments can improve gastrointestinal function in patients with sepsis and gastrointestinal dysfunction, as well as decreasing the incidence of MODS and mortality and improving patient prognosis.

[Survival of bDMARDs in bionaive patients with rheumatoid arthritis: data from a retrospective 12-month follow-up].

AIM: Analysis of survival on biological therapy in previously bionaive patients with rheumatoid arthritis (RA) during the first year of therapy in real clinical practice. MATERIALS AND METHODS: The retrospective study included 204 adult patients with RA. In the hospital, patients were first prescribed therapy with various biological disease-modifying antirheumatic drugs (bDMARDs): infliximab, adalimumab, etanercept, certolizumab pegol, tocilizumab, abatacept (ABA), rituximab (RTM). Patients were divided by age in accordance with the classification adopted by WHO. Clinical forms of RA were presented: RA, seropositive for rheumatoid factor, RA, seronegative for rheumatoid factor, RA with extra-articular manifestations, adult-oneset Stills disease, juvenile RA. The reasons for the cancellation of bDMARD during the first year of treatment were: insufficient effectiveness (including primary inefficiency), adverse events, administrative reasons, clinical and laboratory remission, death. RESULTS: A year after being included in the study, treatment was continued in 92 (45%) patients and was discontinued in 112 patients. The average time of treatment amounted to 0.750.33 years. The longest duration of treatment was in the RTM and ABA groups (0.920.22 and 0.830.29 years, respectively). In 56 (50%) patients, bDMARD was canceled due to insufficient effectiveness (including primary inefficiency), 28 patients (25%) due to the development of adverse reactions, 19 (17%) patients for administrative reasons, 7 (6.25%) patients due to drug remission. During the first year of therapy, there were 2 (1.75%) deaths due to severe comorbid conditions in patients, one of whom received RTM, the other tocilizumab. CONCLUSION: Study showed that 45% of patients with RA continue treatment with first-time bDMARD for more than 12 months. The most common reason for discontinuation of therapy was its lack of effectiveness. The best survival rate of bDMARDs was observed in RTM and ABA. When selecting bDMARD in each case, it is necessary to take into account the continuity at all stages of treatment.

Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE), improved following surgical resection of prostatic carcinoma: A case report.

RS3PE syndrome is a rare condition that occurs in elderly individuals which can present alone or in association with various rheumatic or malignant diseases. We present a case of a 77-year-old man who was diagnosed with adenocarcinoma of the prostate and initially under active surveillance. 2 months after the diagnosis, he presented with arthralgia in both shoulders and knees, pitting edema of the both hands and feet. The patient underwent radical prostatectomy since the link between prostatic carcinoma and RS3PE was suspected. After 7 months from operation, the patient has no symptoms or signs of RS3PE.

Effect of miR-155 on acute lung injury in burned rats: Changes of nuclear factor-kappa B pathway / 中国组织工程研究

BACKGROUND: Currently, studies have focused on the role and mechanism of nuclear factor-kappa B pathway in the pathological process of acute lung injury in burned rats, such as the targeting inhibition of kB kinase by miR-155, which further weakens the activity of nuclear factor-KB and plays a role in acute lung injury in burned rats. However, there are still some pathological mechanisms to be studied and confirmed. OBJECTIVE: To investigate the effect of miR-155 on acute lung injury in burned rats through nuclear factor-KB pathway. METHODS: The rat models of acute lung injury were established by warm water bath simulating bum injury. The burned rats were divided into acute lung injury, miR-155-mimics and miR-155-inhibitor groups. After fluid resuscitation, the rats in the miR-155-mimics and miR-155-inhibitor groups were injected into the tail vein of 5 |_iL of miR-155-mimics and miR-155-inhibitions, respectively. The expression levels of tumor necrosis factor-a and interleukin-1 p in bronchoalveolar lavage fluid were detected by ELISA. The lung morphology in the three groups was observed by hematoxylin-eosin staining. The protein expression levels of nuclear factor-KB and cyclooxygenase 2 were evaluated by western blot assay. The nuclear factor-KB protein in lung tissues was detected by immunohistochemistry. RESULTS AND CONCLUSION: (1) The results of hematoxylin-eosin staining showed that the severity of lung injury in the miR-155-inhibitor group, acute lung injury group and the miR-155-mimics group was increased gradually (P < 0.05). (2) ELISA results showed that compared with the acute lung injury group, the expression levels of tumor necrosis factor-a and interleukin-1 p were increased in the miR-155-mimics group (P < 0.05), and decreased in the miR-155-inhibitor group (P < 0.05). (3) Western blot assay results showed that compared with the acute lung injury group, the expression levels of nuclear factor-KB and cyclooxygenase 2 proteins were increased in the miR-155-mimics group (P < 0.05), and decreased in the miR-155-inhibitor group (P < 0.05). (4) Immunohistochemical results showed that the expression level of nuclear factor-KB was increased in the miR-155-inhibitor group, which was dark brown. The expression of nuclear factor-KB in cytoplasm and nucleus of neutrophils, mononuclear macrophages, alveolar epithelial cells was the most obvious. (5) These results indicate that in lung tissue cells, decreased miR-155 can down-regulate nuclear factor-KB activity, which reduces the inflammatory response of the lung between the damaged tissue. The study was approved by the Laboratory Animal Ethics Committee of the First People’s Hospital of Neijiang, approval No. 1801270.

Peripheral proinflammatory markers are upregulated in abstinent alcohol-dependent patients but are not affected by cognitive bias modification: Preliminary findings.

BACKGROUND: Inflammatory pathways are known to be negatively affected in patients with alcohol use disorder (AUD). Cognitive bias modification (CBM), an emerging behavioral treatment that involves the 're-training' of cognitive biases using computerized tasks, has been reported to reduce alcohol craving and relapse rates. The aim of this study was to compare peripheral concentrations of the proinflammatory biomarkers IL-18, IL-6, IL-1ß, TNF-α and CRP in AUD patients versus controls and to identify whether CBM treatment affected these biomarkers in AUD patients. METHODS: This 3-week double-blind randomized controlled study tested 36 male abstinent AUD patients receiving CBM or placebo-training, who were also compared to 18 male healthy controls. The approach avoidance task (AAT) was used to test the AUD patients before and after training. CBM training took place over 6 sessions, using a joystick-based approach-avoidance task. Blood samples were collected after the pre- and post-AAT test sessions for the AUD groups, and during an outpatient appointment with the controls. RESULTS: AUD patients, versus controls, presented with significantly higher plasma levels of TNF- α (P < 0.0001) and CRP (P = 0.0031). No changes in the CBM versus placebo groups were noted in IL-18, TNF-α and CRP concentrations following pre-post change or within group pretest- posttest analysis. IL-6 and IL-1ß levels fell under the lower detection limit, thus were not included in the final analyses. CONCLUSIONS: This study confirms that the inflammatory system is altered in AUD. This was the first study that investigated whether CBM training affected proinflammatory markers in AUD patients.

Role of matrix metalloproteinases in the pathogenesis of intracranial aneurysms.

Intracranial aneurysms (IAs) are a result of complex interactions between biochemical and mechanical forces and can lead to significant morbidity if they rupture and cause subarachnoid hemorrhage. This review explores the role of matrix metalloproteinases (MMPs) in the pathogenesis and progression of IAs. In addition to providing a review of the normal function of MMPs, it is intended to explore the interaction between inflammation and abnormal blood flow and the resultant pathological vascular remodeling processes seen in the development and rupture of IAs. Also reviewed is the potential for the use of MMPs as a diagnostic tool for assessment of aneurysm development and progression.