Background Vitiligo is an acquired disorder of pigmentation with an elusive pathogenesis, though various theories have been proposed. The presence of peri-lesional autoreactive CD8+ T cell infiltrate suggests the involvement of abnormal immune responses and autoimmunity in vitiligo. Recent studies have identified the IFN-γ-CXCL9/CXCL-10 axis as a key component of the autoimmune response that perpetuates disease activity in vitiligo. Objectives The primary objective was to estimate serum CXCL9 and CXCL10 levels in vitiligo patients compared to age- and sex-matched controls. Additionally, the study aimed to find correlations between CXCL9 and CXCL10 levels and disease severity and stability. Secondary objectives included comparing levels in segmental/nonsegmental vitiligo and stable/progressive vitiligo and assessing the impact of age and gender. Methods A hospital-based cross-sectional study included 60 vitiligo patients and 30 age- and sex-matched controls. Serum levels of CXCL9 and CXCL10 were assessed using Enzyme-linked immunosorbent assay (ELISA). Cases were clinically evaluated for the type of vitiligo (segmental or non-segmental), disease severity (VASI score), and disease stability (VIDA score). Statistical analysis included t-tests, chi-square tests, and correlation coefficients. P value less than 0.5 was taken as significant. Results Serum CXCL9 and CXCL10, both, were significantly raised in vitiligo patients as compared to controls (p-value = 0.001* & 0.001* respectively) and correlated positively with both VASI score (p-value = 0.001* & 0.001* respectively) and with VIDA score (p-value = 0.032* & 0.001* respectively). Serum CXCL10 showed significant elevation in progressive vitiligo, and CXCL9 exhibited a non-significant trend. No significant difference was observed between segmental and non-segmental vitiligo. Both chemokines positively correlated with disease severity and stability, while age and gender did not significantly impact chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlated positively with disease severity & instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. Both serum CXCL9 and CXCL10 were significantly elevated in vitiligo patients compared to controls and they can be used as potential serum biomarkers for assessing the disease activity. Limitations Small sample size of control population. The voluntary sampling technique led to an unequal number of patients in progressive and stable vitiligo groups, as well as in segmental and non-segmental groups. The current study did not include blister fluid analysis and the effect of therapy on the chemokine levels. Conclusion The expression of chemokines CXCL9 and CXCL10 is markedly increased and correlates positively with disease severity and instability, underscoring their mechanistic role in vitiligo pathogenesis. The values were also higher in the progressive group than in the stable group, inferring their conceivable potential as serum biomarkers. *represents statistically significant results.

UNASSIGNED: Carotid endarterectomy (CEA) for the prevention of upcoming vascular and cerebral events is necessary in patients with high-grade stenosis (≥70%). In the framework of the Italian National project Age.It, a pilot study was proposed aiming at the discovery of a molecular signature with predictive potential of carotid stenosis comparing 65+ asymptomatic and symptomatic inpatients.
UNASSIGNED: A total of 42 inpatients have been enrolled, including 26 men and 16 women, with a mean age of 74 ± 6 years. Sixteen symptomatic and 26 asymptomatic inpatients with ≥70% carotid stenosis underwent CEA, according to the recommendations of the European Society for Vascular Surgery and the Society for Vascular Surgeons. Plaque biopsies and peripheral blood samples from the same individuals were obtained. Hematobiochemical analyses were conducted on all inpatients, and plasma cytokines/molecules, such as microRNAs (miRs), IL-6, sIL-6Ralpha, sgp130, myostatin (GDF8), follistatin, activin A, CXCL9, FGF21, and fibronectin, were measured using the ELISA standard technique. MiR profiles were obtained in the discovery phase including four symptomatic and four asymptomatic inpatients (both plasma and plaque samples), testing 734 miRs. MiRs emerging from the profiling comparison were validated through RT-qPCR analysis in the total cohort.
UNASSIGNED: The two groups of inpatients differ in the expression levels of blood c-miRs-126-5p and -1271-5p (but not in their plaques), which are more expressed in symptomatic subjects. Three cytokines were significant between the two groups: IL-6, GDF8, and CXCL9. Using receiver operating characteristic (ROC) analysis with a machine learning-based approach, the most significant blood molecular signature encompasses albumin, C-reactive protein (CRP), the percentage of monocytes, and CXCL9, allowing for the distinction of the two groups (AUC = 0.83, 95% c.i. [0.85, 0.81], p = 0.0028). The potential of the molecular signature will be tested in a second cohort of monitored patients, allowing the application of a predictive model and the final evaluation of cost/benefit for an assessable screening test.

The chemokine (C-X-C) motif ligand 9 (CXCL9) is one of the lymphocyte-traffic-involved chemokines. Despite the immunotherapeutic potential of CXCL9 for recruiting effector T cells (cluster of differentiation 4+ (CD4+) and CD8+ T cells) and natural killer cells (NK cells) around the tumors, practical applications of CXCL9 have been limited because of its immune toxicity and lack of stability in vivo. To overcome these limitations, we designed and synthesized Pt-Te nanorods (PtTeNRs), which exhibited excellent photothermal conversion efficiency with stable CXCL9 payload characteristics under the physiological conditions of in vivo environments. We developed a CXCL9-based immunotherapy strategy by utilizing the unique physicochemical properties of developed PtTeNRs. The investigation revealed that the PtTeNR-loaded CXCL9 was effectively accumulated in the tumor, subsequently released in a sustained manner, and successfully recruited effector T cells for immunotherapy of the designated tumor tissue. In addition, a synergistic effect was observed between the photothermal (PT) therapy and antiprogrammed cell death protein 1 (aPD-1) antibody. In this study, we demonstrated that PtTeNR-based CXCL9, PT, and aPD-1 antibody trimodal therapy delivers an outstanding tumor suppression effect in all stages of cancer, including phases 1-4 and tumor recurrence.

BACKGROUND: Age-associated impairments in innate immunity are believed to be a causative factor responsible for severe pathogenesis of Staphylococcus aureus (S. aureus) infection in the bone tissue. However, the basis for age-associated decline in innate immune response upon S. aureus infection remains poorly understood.
RESULTS: Our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis show up-regulated CXCL9 and CXCL10 (CXCL9/10), which is further confirmed in vitro and in vivo by the present study. Notably, monocytes are a main source for CXCL9/10 production in bone marrow upon S. aureus challenge, but this response declines in middle-aged mice. Interestingly, conditional medium of bone marrow monocytes from middle-aged mice has a strikingly decreased effect on bactericidal functions of neutrophils and macrophages compares with that from young mice. We further show that activation of CXCL9/10-CXCR3 axis between monocytes and macrophages/neutrophils promotes the bactericidal function of the cells, whereas blocking the axis impairs such function. Importantly, treatment with either exogenous CXCL9 or CXCL10 in a middle-aged mice model enhances, while pharmacological inhibition of CXCR3 in young mice model impairs, bacterial clearance and bone marrow structure.
CONCLUSIONS: These findings demonstrate that bone marrow monocytes act as a critical promotor of innate immune response via the CXLCL9/10-CXCR3 axis upon S. aureus infection, and that the increased susceptibility to S. aureus infection in skeleton in an aged host may be largely attributable to the declined induction of CXCR9/10 in monocytes.

BACKGROUND: The aims of this study were to identify clinically significant biomarkers of a response to atezolizumab plus bevacizumab (ATZ + BV) therapy and to develop target strategies against unresectable hepatocellular carcinoma (u-HCC).
METHODS: We first investigated the potential of circulating tumor DNA (ctDNA) to serve as a biomarker for predicting the therapeutic outcome in 24 u-HCC patients treated with ATZ + BV therapy. Next, we analyzed levels of immune-related cytokines in blood samples from 134 u-HCC patients who received ATZ + BV. For this, serum immune-related molecules or cancer-immune cycle-related molecules that have been reported in HCC patient sera, namely CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8 were measured using enzyme-linked immunosorbent assay.
RESULTS: More than 1% of variant read frequency (VRF) mutations were found in TP53, APC, PIK3CA and VHL, although with no correlation with treatment response. Among the 15 cytokines evaluated, CXCL9 and LAG-3 levels were significantly different between patients with objective response (OR), stable disease (SD), and progressive disease (PD) following ATZ + BV treatment. Receiver-operating characteristic curve analyses of CXCL9 (cut-off value: 419.1 pg/ml) and LAG-3 (cut-off value: 3736.3 pg/ml) indicated areas of 0.779 and 0.697, respectively, for differentiating PD from non-PD and OR from non-OR. In multivariate analysis of progression-free survival (PFS) and overall survival (OS), high serum CXCL9 (hazard ratio (HR) and 95% confidence interval (CI): 0.412 (0.251-0.677) (p = 0.0005) for PFS and 0.252 (0.125-0.508) (p = 0.0001) for OS), and low serum LAG-3 (HR and 95% CI 0.419 (0.249-0.705) (p = 0.0011) for PFS and 0.294 (0.140-0.617) (p = 0.0012) for OS) were independent positive predictive factors.
CONCLUSIONS: Although, as far as we examined, no ctDNA mutations in blood were found to be related to ATZ + BV treatment efficacy, serum CXCL9 and LAG-3 levels, which are related to the cancer-immune cycle, were associated with treatment efficacy and could be predictive markers of the efficacy of ATZ + BV treatment in HCC patients.

UNASSIGNED: The expression and function of coexpression genes of M1 macrophage in cervical cancer have not been identified. And the CXCL9-expressing tumour-associated macrophage has been poorly reported in cervical cancer.
UNASSIGNED: To clarify the regulatory gene network of M1 macrophage in cervical cancer, we downloaded gene expression profiles of cervical cancer patients in TCGA database to identify M1 macrophage coexpression genes. Then we constructed the protein-protein interaction networks by STRING database and performed functional enrichment analysis to investigate the biological effects of the coexpression genes. Next, we used multiple bioinformatics databases and experiments to overall investigate coexpression gene CXCL9, including western blot assay and immunohistochemistry assay, GeneMANIA, Kaplan-Meier Plotter, Xenashiny, TISCH2, ACLBI, HPA, TISIDB, GSCA and cBioPortal databases.
UNASSIGNED: There were 77 positive coexpression genes and 5 negative coexpression genes in M1 macrophage. The coexpression genes in M1 macrophage participated in the production and function of chemokines and chemokine receptors. Especially, CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 expression would significantly decrease and high CXCL9 levels were linked to good prognosis in the cervical cancer tumour patients, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. The CXCL9 gene interaction network could regulate immune-related signalling pathways, and CXCL9 amplification was the most common mutation type in cervical cancer. Meanwhile, CXCL9 may had clinical significance for the drug response in cervical cancer, possibly mediating resistance to chemotherapy and targeted drug therapy.
UNASSIGNED: Our findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms in cervical cancer, and indicated that M1 macrophage association gene CXCL9 may serve as a good prognostic gene and a potential therapeutic target for cervical cancer therapies.
Cervical cancer is a common gynaecological malignancy, investigating the precise gene expression regulation of M1 macrophage is crucial for understanding the changes in the immune microenvironment of cervical cancer. In our study, a total of 82 coexpression genes with M1 macrophages were identified, and these genes were involved in the production and biological processes of chemokines and chemokine receptors. Especially, the chemokine CXCL9 was positively correlated with M1 macrophage infiltration levels in cervical cancer. CXCL9 as a protective factor, it manifestly expressed in blood immune cells, and was positively related to immune checkpoints. CXCL9 amplification was the most common type of mutation. And CXCL9 expression could have an effect on the sensitivity of some chemicals or targeted drugs against cervical cancer. These findings may provide new insight into the M1 macrophage coexpression gene network and molecular mechanisms, and shed light on the role of CXCL9 in cervical cancer.

Background: The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9 expression and prognosis in triple-negative breast cancer (TNBC) is unclear. Methods: We investigated CXCL9 mRNA expression, clinicopathological features, and prognosis in TNBC patients. We also used computational image analysis to quantify and assess the distribution of CXCL9 protein in the tumor core (TC) and invasive margin (IM). Results: CXCL9 mRNA expression was significantly higher in TNBC tumors compared to normal tissue (p < 0.001) and was associated with smaller tumors (p = 0.022) and earlier stages (p = 0.033). High CXCL9 mRNA expression was correlated with improved overall survival (OS) in three independent cohorts (all p < 0.05). In a separate analysis, low CXCL9 protein expression was associated with increased lymph node metastasis (p = 0.018 and p = 0.036). High CXCL9 protein expression in the TC, IM, or both was associated with prolonged OS (all p < 0.001). Conclusion: High CXCL9 expression, at both the mRNA and protein levels, is associated with improved prognosis in TNBC patients. CXCL9 expression in the TC and/or IM may be an independent prognostic factor.

Dengue fever poses a significant global health threat, with symptoms including dengue hemorrhagic fever and dengue shock syndrome. Each year, India experiences fatal dengue outbreaks with severe manifestations. The primary cause of severe inflammatory responses in dengue is a cytokine storm. Individuals with a secondary dengue infection of a different serotype face an increased risk of complications due to antibody-dependent enhancement. Therefore, it is crucial to identify potential risk factors and biomarkers for effective disease management. In the current study, we assessed the prevalence of dengue infection in and around Aligarh, India, and explored the role of cytokines, including CXCL5, CXCL9, and CCL17, in primary and secondary dengue infections, correlating them with various clinical indices. Among 1,500 suspected cases, 367 tested positive for dengue using Real-Time PCR and ELISA. In secondary dengue infections, the serum levels of CXCL5, CXCL9, and CCL17 were significantly higher than in primary infections (P < 0.05). Dengue virus (DENV)-2 showed the highest concentrations of CXCL5 and CCL17, whereas DENV-1 showed the highest concentrations of CXCL9. Early detection of these cytokines could serve as potential biomarkers for diagnosing severe dengue, and downregulation of these cytokines may prove beneficial for the treatment of severe dengue infections.

UNASSIGNED: Vitiligo is a chronic, autoimmune condition characterized by skin depigmentation caused by inflammatory-mediated melanocyte degradation. Treatment of vitiligo is challenging due to the chronic nature of the condition. Ruxolitinib cream 1.5% was recently approved by the Food and Drug Administration (FDA) as a Janus kinase 1 and 2 inhibitor for use in nonsegmental vitiligo for those 12 years and older.
UNASSIGNED: The purpose of this review is to describe the role of ruxolitinib in treating nonsegmental vitiligo.We searched PubMed using search terms nonsegmental vitiligo, jak inhibitor, and ruxolitinib. Clinicaltrials.gov was used to identify clinical trial data including efficacy, pharmacodynamics, pharmacokinetics, safety, and tolerability.
UNASSIGNED: In both phase II and phase III (TRuE-V1 and TRuE-V2) trials, ruxolitinib cream 1.5% improved repigmentation with minimal adverse effects. Topical ruxolitinib is a much needed new vitiligo treatment option.  Real life efficacy may not match that seen in clinical trials if the hurdle of poor adherence to topical treatment is not surmounted.

BACKGROUND: The severity and clinical outcome of COVID-19 depend on virus-specific factors and the host\'s inflammatory response. Identifying biomarkers of severe COVID-19 is a crucial condition and predicts disease severity.
METHODS: This study enrolled a total of 167 patients with COVID-19. These patients were categorized into three groups based on the severity of the disease: moderate course - 78 individuals, severe course - 52 individuals, and extremely severe course - 37 individuals. We analyzed chemokines (IP-10, CXCL9, CCL17) and cytokine IL28B levels using the enzyme immunoassay (EIA) method.
RESULTS: CXCL9 levels were increased in severe and extremely severe cases compared to moderate ones. The CCL17 chemokine demonstrated significant elevation in severe cases. However, there was no significant difference in the level of IP-10, and IL28B in the compared groups.
CONCLUSIONS: Our findings suggest that CXCL9 and CCL17 chemokines could be used as biomarkers to assess the clinical status of patients with COVID-19 and can relate to disease severity. These biomarkers could aid in identifying patients at high risk for severe disease and help guide clinical decision-making for the effective management of COVID-19.