Measuring serum and drainage fluid interleukin-6 and tumor necrosis factor-α levels for early detection of infectious complications after minimally invasive surgery for gastric cancer.

OBJECTIVE: Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are inflammatory cytokines produced in response to biological invasion or infection. Their levels are elevated in the blood and locally. We examined whether measuring IL-6 and TNF-α levels in serum or drainage fluid on postoperative day (POD) 1 could detect infectious complications after minimally invasive surgery for gastric cancer. METHODS: This cohort study included 205 consecutive patients who underwent laparoscopic or robot-assisted gastrectomy for gastric cancer between November 2020 and July 2023. We measured serum and drainage fluid IL-6 and TNF-α levels on POD 1 after gastrectomy. Receiver operating characteristic (ROC) curves were created to compare the diagnostic values of each cytokine and serum C-reactive protein levels for detecting postoperative infectious complications. RESULTS: IL-6 and TNF-α levels in the serum or drainage fluid were significantly higher in patients with an infectious complication. In addition, drainage fluid IL-6 levels were significantly different in patients with versus without intra-abdominal abscess. In the ROC curve analysis, serum and drainage fluid IL-6 had the highest AUC values for any infectious complication and intra-abdominal abscess, respectively. POD 1 serum IL-6 level above 47 pg/mL could detect any infectious complication with sensitivity of 74.1 % and specificity of 71.8 %. POD 1 drainage fluid IL-6 level above 14,750 pg/mL had 100 % sensitivity for detecting intra-abdominal abscess with specificity of 56.0 %. CONCLUSIONS: Measurement of IL-6 levels in blood and drainage fluid on POD 1 is valuable for early detection of postoperative infectious complications or intra-abdominal abscess after gastric cancer surgery.

Examining the moderating role of cannabis use on the relationship between alcohol consumption and inflammation in individuals with alcohol use disorder.

Inflammation appears to be a critical mechanism in the development of alcohol use disorder (AUD) and a consequence of chronic alcohol use. The potential anti-inflammatory properties of cannabis may modulate the proinflammatory effects of alcohol. This study sought to extend previous work investigating the relationship between alcohol consumption, cannabis use and circulating interleukin (IL)-6 levels in a sample with AUD. One hundred and thirty-three individuals with an AUD provided blood samples to assess IL-6 and answered questions regarding alcohol and cannabis use. An ordinary least squares multiple regression analysis was conducted to assess the effect of alcohol and cannabis use on IL-6. A moderation analysis examined cannabis use as a potential moderator of the relationship between alcohol use and circulating IL-6 levels. Alcohol use was predictive of higher log IL-6 levels (standardized ß = 0.16, p = 0.03), while cannabis use was not predictive of log IL-6 levels (p = 0.36). Days of cannabis use moderated the relationship between alcohol use and IL-6 levels, such that the relationship between alcohol use and IL-6 levels was only significant in individuals with AUD without recent cannabis use. This study extends previous work to a clinical sample with an AUD and underscores the importance of considering cannabis use in studies on alcohol use and inflammation. This study also indicates the need for in-depth analyses on cannabinoids and inflammation and the interaction between cannabinoids and alcohol use on inflammation.

The role of TNF-α and il-6 SNP in polycystic ovary syndrome susceptibility.

OBJECTIVE: Aim: To shed the light on the impact of TNF-α 1031 T/C (rs-1800629) and IL-6 174 G/C (rs1800795) polymorphism with disease susceptibility and development. PATIENTS AND METHODS: Materials and Methods: A case-control study has been established based on 50 women with confirmed diagnosed polycystic ovarian syndrome, and 50 healthy controls. Allele specific PCR have been done in order to study SNP of TNF-alpha and IL-6 in both groups. RESULTS: Result: The findings of the present investigation indicated that there was a signif i cant dif f erence in the frequency distribution of TNF-alpha 1031 T/C SNP according to genotype between patients and controls group p = 0.02. In addition, there is a high significant difference in the frequencies of distribution of alleles (T/C) between patients and control group p = 0.001. There was a signif i cant dif f erence in the frequency distribution of IL-6 174 G/C between patients and controls group p = 0.026. In addition, there is a signif i cant dif f erence in the frequencies of distribution of participants according to allele (G/C) between patients and control group p = 0.047. Genotype GC was significantly lower in patients' group and genotype GG was high significant in patients' group in comparison with a control group and the differences were significant, p = 0.024 and 0.006, respectively. CONCLUSION: Conclusions: The present study concluded that IL-6 174 G/C, (rs:1800795) single nucleotide polymorphism (SNP) and TNF-alpha 1031 T/C (rs-1800629) were associated with PCOS susceptibility, and GG genotype in IL-6 and C allele in TNF are considered as risk factor.

Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Prognostic value of inflammatory cytokine detection for sepsis patients in ICU: a meta-analysis.

OBJECTIVE: To explore the prognostic effect of cytokine levels such as IL-6 (interleukin), IL-8 and TNF (tumor necrosis factor)-α on patients with sepsis in intensive care units (ICUs) by Meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and other databases up to May 2023 to retrieve clinical research articles on cytokine testing for predicting sepsis prognosis in ICU settings. Relevant indicators were extracted and recorded in Excel. Meta-analyses were performed using RevMan 5.3. RESULTS: A total of 25 studies were finally included in this Meta-analysis: 21 investigated IL-6, 6 examined IL-8, 11 addressed IL-10, 12 reviewed TNF-α, and 6 focused on IL-1ß. Meta-analysis results demonstrated that cytokine levels (IL-6, IL-8, IL-10, TNF-α and IL-1ß) in survival groups were substantially lower than those in non-survival groups (ALL P < 0.00001). Specific findings include significant differences in IL-6 [SMD = -25.32, 95% CI (-27.14, -23.49), P < 0.00001], IL-8 [SMD = -140.48, 95% CI (-154.32, -126.64), P < 0.00001], IL-10 [SMD = -54.10, 95% CI (-56.74, -51.47), P < 0.00001], TNF-α [SMD = -8.67, 95% CI (-9.82, -7.52), P < 0.00001], and IL-1ß [SMD = -3.71, 95% CI (-4.11, -3.30), P < 0.00001]. The funnel plots for IL-6, IL-8, IL-10, TNF-α, and IL-1ß displayed roughly symmetrical distributions, suggesting minimal bias and high reliability of the findings. CONCLUSION: Cytokine levels such as IL-6, IL-8, and TNF-α are valuable prognostic indicators for patients with sepsis in the ICUs. Early testing of these cytokines can guide clinical interventions and enable targeted treatments for high-risk patients to reduce the likelihood of adverse outcomes.

Association of interleukin6 rs1800796 gene polymorphism and serum level with bladder cancer in Egyptian population.

BACKGROUND: Urinary bladder cancer (UBC)is a common tumor of the urinary tract. OBJECTIVES: To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. DESIGN AND METHODS: One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. RESULTS: The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. CONCLUSION: It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.

Mitigating target interference challenges in bridging immunogenicity assay to detect anti-tocilizumab antibodies.

Aim: An assay to detect anti-tocilizumab antibodies in the presence of high levels of circulating target and drug is needed for immunogenicity assessment in comparative clinical studies. Methods: An assay was developed and validated using a combination of blocking agents and dilutions to overcome target interference challenges. Results: No false-positive signal was detected in serum samples spiked with 350-500 ng/ml of IL-6 receptor. As low as 50 ng/ml of positive control antibodies could be detected in the presence of either 500 ng/ml of IL-6 or 250 µg/ml of the drug product. Assay also demonstrated high sensitivity, selectivity and precision. Conclusion: A robust, easy to perform immunogenicity assay was developed and validated for detecting anti-tocilizumab antibodies.

[Box: see text].

Safety and Effectiveness of Satralizumab in Japanese Patients with Neuromyelitis Optica Spectrum Disorder: A 6-month Interim Analysis of Post-marketing Surveillance.

INTRODUCTION: Satralizumab, an anti-interleukin-6 receptor antibody, is approved in Japan for relapse prevention in neuromyelitis optica spectrum disorder (NMOSD) and is undergoing post-marketing surveillance (PMS) of clinical use. We aimed to describe the real-world safety and effectiveness of satralizumab in Japanese patients with NMOSD. METHODS: This is an ongoing PMS (planned completion: February 2027). This 6-month interim analysis assessed the safety and effectiveness of satralizumab in Japanese patients with NMOSD using data collected from August 2020 to July 2021. RESULTS: Among 570 patients who participated, 523 (91.75%) were female and the mean ± standard deviation (SD) age was 52.4 ± 14.1 years. At baseline, NMOSD expanded disability status scale mean ± SD was 4.19 ± 2.19; 490 (85.96%) patients used glucocorticoids and 277 (48.59%) patients used immunosuppressants concomitantly. Of 570 satralizumab-treated patients, 85 (14.91%) had discontinued satralizumab treatment at 6 months. For the overall adverse drug reactions (ADRs), 76.22 (66.07-87.48) events/100 person-years occurred in 118 (20.70%) patients, and infections occurred in 28 (4.91%) patients. Serious infections occurred in 18 (3.15%) patients, with an event rate of 9.05 (5.80-13.47) events/100 person-years. Of the 24 events of serious infections, respiratory tract infections (29.17%; 7) and urinary tract infections (25.00%; 6) were the most common serious infection events. One fatal ADR (septic shock) suspected to be related to satralizumab was reported. The mean ± SD glucocorticoid dose reduced from 12.28 ± 10.17 mg/day at the index date to 8.11 ± 7.30 mg/day at 6 months. The Kaplan-Meier cumulative relapse-free rate (95% confidence interval) was 94.59% (92.25-96.23) at 6 months. CONCLUSION: In this study, satralizumab was found to be safe, well tolerated, and effective in patients with NMOSD in routine clinical practice. The results are consistent with those of previous clinical trials. The safety and effectiveness of satralizumab in Japanese patients with NMOSD will be analyzed over the 6-year surveillance period. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000041047.

Antioxidant, Anti-Inflammation, and Melanogenesis Inhibition of Sang 5 CMU Rice (Oryza sativa) Byproduct for Cosmetic Applications.

Prolonged exposure to environmental oxidative stress can result in visible signs of skin aging such as wrinkles, hyperpigmentation, and thinning of the skin. Oryza sativa variety Sang 5 CMU, an inbred rice cultivar from northern Thailand, contains phenolic and flavonoid compounds in its bran and husk portions that are known for their natural antioxidant properties. In this study, we evaluated the cosmetic properties of crude extracts from rice bran and husk of Sang 5 CMU, focusing on antioxidant, anti-inflammatory, anti-melanogenesis, and collagen-regulating properties. Our findings suggest that both extracts possess antioxidant potential against DPPH, ABTS radicals, and metal ions. Additionally, they could downregulate TBARS levels from 125% to 100% of the control, approximately, while increasing the expression of genes related to the NRF2-mediated antioxidant pathway, such as NRF2 and HO-1, in H2O2-induced human fibroblast cells. Notably, rice bran and husk extracts could increase mRNA levels of HO-1 more greatly than the standard L-ascorbic acid, by about 1.29 and 1.07 times, respectively. Furthermore, the crude extracts exhibited anti-inflammatory activity by suppressing nitric oxide production in both mouse macrophage and human fibroblast cells. Specifically, the bran and husk extracts inhibited the gene expression of the inflammatory cytokine IL-6 in LPS-induced inflammation in fibroblasts. Moreover, both extracts demonstrated potential for inhibiting melanin production and intracellular tyrosinase activity in human melanoma cells by decreasing the expression of the transcription factor MITF and the pigmentary genes TYR, TRP-1, and DCT. They also exhibit collagen-stimulating effects by reducing MMP-2 expression in H2O2-induced fibroblasts from 135% to 80% of the control, approximately, and increasing the gene associated with type I collagen production, COL1A1. Overall, the rice bran and husk extracts of Sang 5 CMU showed promise as effective natural ingredients for cosmetic applications.

Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period.

Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system's role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.

A Positive Feedback Loop Exists between Estradiol and IL-6 and Contributes to Dermal Fibrosis.

Systemic sclerosis (SSc) is characterized by dermal fibrosis with a female predominance, suggesting a hormonal influence. Patients with SSc have elevated interleukin (IL)-6 levels, and post-menopausal women and older men also have high estradiol (E2) levels. In the skin, IL-6 increases the enzymatic activity of aromatase, thereby amplifying the conversion of testosterone to E2. Therefore, we hypothesized that an interplay between E2 and IL-6 contributes to dermal fibrosis. We used primary dermal fibroblasts from healthy donors and patients with diffuse cutaneous (dc)SSc, and healthy donor skin tissues stimulated with recombinant IL-6 and its soluble receptor (sIL-6R) or E2. Primary human dermal fibroblasts and tissues from healthy donors stimulated with IL-6+sIL-6R produced E2, while E2-stimulated dermal tissues and fibroblasts produced IL-6. Primary dermal fibroblasts from healthy donors treated with IL-6+sIL-6R and the aromatase inhibitor anastrozole (ANA) and dcSSc fibroblasts treated with ANA produced less fibronectin (FN), type III collagen A1 (Col IIIA1), and type V collagen A1 (Col VA1). Finally, dcSSc dermal fibroblasts treated with the estrogen receptor inhibitor fulvestrant also generated less FN, Col IIIA1, and Col VA1. Our data show that IL-6 exerts its pro-fibrotic influence in human skin in part through E2 and establish a positive feedback loop between E2 and IL-6.

miR-338-5p regulated the NF-κB/MAPK pathway to alleviate inflammation and oxidative stress by targeting IL-6 in rats with atrial fibrillation.

The aim of this study was to investigate the functional effect of miR-338-5p targeting IL-6 on NF-κB/MAPK pathway-mediated inflammation and oxidative stress in atrial fibrillation (AF) rats. AF model rats were generated by tail vein injection of 0.1 mL Ach-CaCl2 mixture. The overexpression and suppression of miR-338-5p were established by injecting a miR-338-5p-agomir and a miR-338-5p-antagomir, respectively, into AF rats. Cardiac morphological changes were detected by H&E and Masson staining. The levels of ROS, SOD, T-AOC, IL-6, IL-1ß, and TNF-α were detected via ELISA. Dual luciferase assays, qRT‒PCR, and western blotting were used to verify that miR-338-5p targets IL-6. The expression of NF-κB/MAPK pathway proteins was detected by western blot. Overexpression of miR-338-5p ameliorated heart damage in AF rats. Increased miR-338-5p reduced the levels of CK, CK-MB, and cTnT to alleviate myocardial injury. Furthermore, overexpression of miR-338-5p relieved inflammation and oxidative stress by downregulating SOD and T-AOC and upregulating IL-6, IL-1ß, TNF-α, and ROS. Further research revealed that upregulation of miR-338-5p reduced the protein levels of p-p38, p-p65 and p-ERK1/2. The opposite results were obtained following miR-338-5p-antagomir treatment. Taken together, these findings indicate that the upregulation of miR-338-5p alleviated inflammation and oxidative stress by targeting IL-6 to inhibit the NF-κB/MAPK pathway, thus providing a new therapeutic target for AF.

Pro- and anti-inflammatory cytokines signatures at different severity of dengue infection.

Context: Dengue disease severity and progression are determined by the host immune response, with both pro- and anti-inflammatory cytokines are key mediators. Aims: To study pro- and anti-inflammatory cytokines across dengue severity and as a biomarker for predicting severe dengue infection. Settings and Design: Hospital-based cross-sectional study was conducted on 125 dengue-positive subjects across the 5-60 years age group of either gender in 2022. Methods and Materials: Haematological parameters and blood samples were drawn to measure cytokines IL6, IL-10 and TNF alpha using the ELISA technique. Statistical Analysis: One-way ANOVA and the Kruskal - Wallis test were used to compare the dependent variables across categories of the dengue spectrum. Receiver operating characteristic curve was drawn to calculate the predictability of the cytokines as a predictor of severe dengue. A P < 0.05 was considered significant. Results: 34.4% of cases had severe dengue infection with 53.2% of severe cases reported in >40 years of age. Only IL-6 levels significantly increased (P < 0.01) across the spectrum of dengue infection across age groups >20 years with a consistent and significant fall in platelet levels (P < 0.01). The accuracy of IL-6 to predict severe dengue was 74.4% and platelet count was 16.2%. Conclusions: Only IL-6 cytokine levels were significantly increased across the spectrum of dengue infection observed in age >20 years and can significantly predict the probability of severe dengue by 74% (sensitivity 81.4%). A significant decrease in platelet values is consistent with the severity but is not a good predictor for severe dengue infection.

Deleterious Anti-Inflammatory Macrophage Recruitment in Early Post-Infarction Phase: Unraveling the IL-6/MCP-1/STAT3 Axis.

Using a translational approach with an ST-segment myocardial infarction (STEMI) cohort and mouse model of myocardial infarction, we highlighted the role of the secreted IL-6 and MCP-1 cytokines and the STAT3 pathway in heart macrophage recruitment and activation. Cardiac myocytes secrete IL-6 and MCP-1 in response to hypoxic stress, leading to a recruitment and/or polarization of anti-inflammatory macrophages via the STAT3 pathway. In our preclinical model of myocardial infarction, neutralization of IL-6 and MCP-1 or STAT3 pathway reduced infarct size. Together, our data demonstrate that anti-inflammatory macrophages can be deleterious in the acute phase of STEMI.

Childhood sexual abuse and IL6 mediated by change in BMI over an 18-year period: A growth curve model.

BACKGROUND: Childhood sexual abuse can increase both body weight and inflammation later in life. Higher weight or faster changes in weight, as measured by changes in body mass index (BMI), may mediate the relationship between childhood sexual abuse and inflammation, however, most studies to date have used a cross-sectional design limiting causal inferences. OBJECTIVE: The current study aimed to investigate the interrelationships between childhood sexual abuse, BMI, and C-reactive protein (CRP) and interleukin-6 (IL6). PARTICIPANTS AND SETTING: Data from 461 adults who participated in the Midlife in the United States (MIDUS) study were utilized. METHODS: Growth curve modeling was used to test initial levels of BMI and changes of BMI over an 18-year period as mediators linking childhood sexual abuse to CRP and IL6. RESULTS: Sexual abuse was not significantly associated with the initial level of BMI; however, sexual abuse was associated with the slope of BMI (b = 0.072, p = .006). BMI intercept (b = 0.080, p = .001) and slope (b = 0.240, p = .002) predicted IL6 values whereas the slope of BMI (b = 0.398, p = .033) but not intercept predicted CRP values. The indirect effect from sexual abuse to IL6 through BMI slope was significant (b = 0.017, 95 % [CI.001, 0.033]) while the indirect effect from sexual abuse to CRP through BMI slope was not significant (b = 0.028, 95 % [CI -0.004, 0.061]). CONCLUSION: Childhood sexual abuse was indirectly associated with IL6 through rates of change in BMI over time.

Jiawei Duhuo Jisheng Mixture Mitigates Osteoarthritis Progression in Rabbits by Inhibiting Inflammation: A Network Pharmacology and Experimental Approach.

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear. OBJECTIVE: This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models. METHODS: The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings. RESULTS: Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1ß, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls. CONCLUSION: JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.

Cigarette smoke promotes IL-6-dependent lung cancer migration and osteolytic bone metastasis.

Lung cancer stands as a major contributor to cancer-related fatalities globally, with cigarette smoke playing a pivotal role in its development and metastasis. Cigarette smoke is also recognized as a risk factor for bone loss disorders like osteoporosis. However, the association between cigarette smoke and another bone loss disorder, lung cancer osteolytic bone metastasis, remains largely uncertain. Our Gene Set Enrichment Analysis (GSEA) indicated that smokers among lung cancer patients exhibited higher expression levels of bone turnover gene sets. Both The Cancer Genome Atlas (TCGA) database and our clinic samples demonstrated elevated expression of the osteolytic factor IL-6 in ever-smokers with bone metastasis among lung cancer patients. Our cellular experiments revealed that benzo[α]pyrene (B[α]P) and cigarette smoke extract (CSE) promoted IL-6 production and cell migration in lung cancer. Activation of the PI3K, Akt, and NF-κB signaling pathways was involved in cigarette smoke-augmented IL-6-dependent migration. Additionally, cigarette smoke lung cancer-secreted IL-6 promoted osteoclast formation. Importantly, blocking IL-6 abolished cigarette smoke-facilitated lung cancer osteolytic bone metastasis in vivo. Our findings provide evidence that cigarette smoke is a risk factor for osteolytic bone metastasis. Thus, inhibiting IL-6 may be a valuable therapeutic strategy for managing osteolytic bone metastasis in lung cancer patients who smoke.

Fulminant demyelinating disease of the central nervous system effectively treated with a combination of decompressive craniectomy and immunotherapy: A case report and literature review.

Key Clinical Message: Accurately identifying fulminant demyelinating diseases is important for sudden onset of asymmetric cerebral white matter lesions with mass effect. Initially, immunotherapy should be administered; however, surgical intervention should be performed with poor response to medical management and evident signs of cerebral herniation. Abstract: A case of fulminant demyelinating disease of the central nervous system that required decompressive craniectomy 8 days after symptom onset is presented. The patient recovered without sequelae after a combination of neurosurgery and immunotherapy with steroids and has remained relapse-free for 4 years.