OBJECTIVE: MCP-1 has been shown to be elevated in endometriosis. ILK functions in several cellular events and interacts with MCP-1-signaling. In the current study, we evaluated the role of MCP-1-ILK signaling in human endometriotic cell\'s (Hs832(C).TCs) potential for colonization, invasion, adhesion, etc. and differentiation of macrophage along with inflammation in an endometriosis mouse model.
METHODS: A mouse model of endometriosis with elevated levels of MCP-1 was developed by injecting MCP-1. We examined the migration, adhesion, colonization and invasion of Hs832(C).TCs in response to MCP-1-ILK signaling. We also examined the differentiation of THP-1 cells to macrophage in response to MCP-1-ILK signaling.
RESULTS: We observed that MCP-1 increased Ser246 phosphorylation of ILK in Hs832(C).TCs and enhanced the migration, adhesion, colonization, and invasion of Hs832(C).TCs. In the mouse model of endometriosis, we found elevated chemokines (CCL-11, CCL-22 and CXCL13) levels. An increased level of MCP-1 mediated ILK activation, leading to increased inflammatory reaction and infiltration of residential and circulatory macrophages, and monocyte differentiation, but suppressed the anti-inflammatory reaction. The inhibitor (CPD22) of ILK reversed the MCP-1-mediated action by restoring Hs832(C).TCs and THP-1 phenotype. ILK inhibition in a mouse model of endometriosis reduced the effects of MCP-1 mediated pro-inflammatory cytokines, but increased anti-inflammatory response along with T-regulatory and T-helper cell restoration.
CONCLUSIONS: Targeting ILK restores MCP-1 milieu in the peritoneal cavity and endometrial tissues, reduces the inflammatory response, improves the T-regulatory and T-helper cells in the endometriosis mouse model and decreases the migration, adhesion, colonization and invasion of endometriotic cells.

OBJECTIVE: In the knee, synovial fibrosis after ligamentous injury is linked to progressive joint pain and stiffness. The objective of this study was to evaluate changes in synovial architecture, mechanical properties, and transcriptional profiles following naturally occurring cruciate ligament injury in canines and to test potential therapeutics that target drivers of synovial inflammation and fibrosis.
METHODS: Synovia from canines with spontaneous cruciate ligament tears and from healthy knees were assessed via histology (n = 10/group) and micromechanical testing (n = 5/group) to identify changes in tissue architecture and stiffness. Additional samples (n = 5/group) were subjected to RNA-sequencing to define the transcriptional response to injury. Finally, synovial tissue samples from injured animals (n = 6 (IL1) or n = 8 (IL6)/group) were assessed in vitro for response to therapeutic molecules directed against interleukin (IL) signaling (IL1 or IL6).
RESULTS: Cruciate injury resulted in increased synovial fibrosis, vascularity, inflammatory cell infiltration, and intimal hyperplasia. Additionally, the stiffness of both the intima and subintima regions were higher in diseased compared to healthy tissue. Differential gene expression analysis showed that diseased synovium had an upregulation of immune response and cell adhesion pathways and a downregulation of Rho protein transduction pathways. In vitro application of small molecule therapeutics targeting IL1 (anakinra) or IL6 (tocilizumab) dampened expression of inflammatory and matrix deposition mediators.
CONCLUSIONS: Spontaneous cruciate ligament injury in canines is associated with synovial inflammation and fibrosis in a relevant model for testing emerging intra-articular treatments. Small molecule therapeutics targeting IL pathways may be ideal interventions for delivery to the joint space after injury.

In this manuscript, we have numerically investigated and experimentally verified the six-element split ring resonator and circular patch-shaped multiple input, multiple output antenna operating in the 1-25 GHz band. MIMO antennas are analyzed in terms of several physical parameters, such as reflectance, gain, directivity, VSWR, and electric field distribution. The parameters of the MIMO antenna, for instance, the envelope correlation coefficient (ECC), channel capacity loss (CCL), the total active reflection coefficient (TARC), directivity gain (DG), and mean effective gain (MEG), are also investigated for identification of a suitable range of these parameters for multichannel transmission capacity. Ultrawideband operation at 10.83 GHz is possible for the theoretically designed and practically executed antenna with the return loss and gain values of -19 dB and -28 dBi, respectively. Overall, the antenna offers minimum return loss values of -32.74 dB for the operating band of 1.92 to 9.81 GHz with a bandwidth of 6.89 GHz. The antennas are also investigated in terms of a continuous ground patch and a scattered rectangular patch. The proposed results are highly applicable for the ultrawideband operating MIMO antenna application in satellite communication with C/X/Ku/K bands.

This paper presents a printed multiple-input multiple-output (MIMO) antenna with the advantages of compact size, good MIMO diversity performance and simple geometry for fifth-generation (5G) millimeter-wave (mm-Wave) applications. The antenna offers a novel Ultra-Wide Band (UWB) operation from 25 to 50 GHz, using a Defective Ground Structure (DGS) technology. Firstly, its compact size makes it suitable for integrating different telecommunication devices for various applications, with a prototype fabricated having a total size of 33 mm × 33 mm × 0.233 mm. Second, the mutual coupling between the individual elements severely impacts the diversity properties of the MIMO antenna system. An effective technique of orthogonally positioning the antenna elements to each other increased their isolation; thus, the MIMO system provides the best diversity performance. The performance of the proposed MIMO antenna was investigated in terms of S-parameters and MIMO diversity parameters to ensure its suitability for future 5G mm-Wave applications. Finally, the proposed work was verified by measurements and exhibited a good match between simulated and measured results. It achieves UWB, high isolation, low mutual coupling, and good MIMO diversity performance, making it a good candidate and seamlessly housed in 5G mm-Wave applications.

UNASSIGNED: To elucidate the cellular mechanisms of polyherbal formulation [Kolin PlusTM (KP)], genomics was performed to delineate the genes and pathways associated with lipid regulation through transcriptional profiling of the liver in commercial broilers raised on diets deficient in choline chloride (CCL).
UNASSIGNED: The gene expression patterns were studied for four groups [normal diet: normal, choline chloride deficient (CCD), KP (400 gm/ton), and CCL (400 gm/ton)] using Agilent microarray on day 42. The hierarchical cluster analysis was carried out on 12,614 differentially expressed genes (DEGs) with a similar expression.
UNASSIGNED: Out of 12,614 significant DEGs, 1,926, 448, and 1,330 genes were expressed at higher rates, and 413, 482, and 1,364 were expressed at lower rates than CCD (CCD vs. normal), CCL (CCL vs. CCD), and KP (KP vs. CCD), respectively. GO enrichment analysis of DEG further revealed the significant association of biological process items with the lipid, sterol, and lipoprotein metabolic processes. In particular, peroxisome proliferator-activated receptor gamma coactivator 1 alpha, carnitine palmitoyl transferase I, hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta, and patatin-like phospholipase domain containing 2 genes involved in fatty acid oxidation and lipase C, ABCG5, ABCG8, acetyl-CoA carboxylase, ATP citrate lyase enzyme, and peroxisome proliferator-activated receptor gamma genes involved in lipogenesis were altered by KP intervention for lipid metabolism.
UNASSIGNED: These findings reveal that the supplementation of KP prevents fatty liver-associated problems in broiler chickens by modulating the expression of the above-mentioned genes that are responsible for the oxidation of fatty acids and lipogenesis in the liver.

In this paper, a novel microstrip line-fed meander-line-based four-elements quad band Multiple Input and Multiple Output (MIMO) antenna is proposed with a gain enhancement technique. The proposed structure resonates at four bands simultaneously, that is, 1.23, 2.45, 3.5 and 4.9 GHz, which resemble GPS L2, Wi-Fi, Wi-MAX and WLAN wireless application bands, respectively. The unit element is extended to four elements MIMO antenna structure exhibiting isolation of more than 22 dB between the adjacent elements without disturbing the resonant frequencies. In order to enhance the gain, two orthogonal microstrip lines are incorporated between the antenna elements which result in significant gain improvement over all the four resonances. Furthermore, the diversity performance of the MIMO structure is analyzed. The Envelope Co-Relation Coefficient (ECC), Diversity Gain (DG), Channel Capacity Loss (CCL), Mean Effective Gain (MEG) and Multiplexing Efficiency are obtained as 0.003, 10 dB, 0.0025 bps/Hz, -3 dB (almost) and 0.64 (min.), respectively, which are competent and compatible with practical wireless applications. The Total Active Reflection Coefficient (TARC) resembles the characteristic of the individual antenna elements. The layout area of the overall MIMO antenna is 0.33 λ × 0.29 λ, where λ is the free-space wavelength corresponding to the lowest resonance. The advantage of the proposed structure has been assessed by comparing it with previously reported MIMO structures based on number of antenna elements, isolation, gain, CCL and compactness. A prototype of the proposed MIMO structure is fabricated, and the measured results are found to be aligned with the simulated results.

Head and neck squamous cell carcinoma (HNSCC) is considered an immunosuppressive malignancy. Cross-talk between cancer cells and immune cells is modulated in part by CC ligand (CCL) chemokines, having a major effect on tumor progression. However, the predictive value and function of CCL family members in HNSCC have not been elucidated. Here, the predictive value of CCL members in cancer prognosis and Immune checkpoint blockade therapy response was investigated. CCL17 and CCL22 were screened as the key CCL chemokines in HNSCC through co-expression analysis. Further, the correlation between CCL17/CCL22 expression and cancer immune infiltration were evaluated based on TIMER and were validated by a set of scRNA-seq data. Moreover, the expression level of CCL17/CCL22 we evaluated to predict the response to Immune checkpoint blockade therapy in a panel of cancer types by using the TIDE database. Results indicated that CCL17/CCL22 had a high co-expression correlation and had a marginally statistical significance with the overall survival in HNSCC patients (P value = 0.057 and 0.055, respectively). Our findings showed high expression of CCL17/CCL22 was positively correlated with CD4+ T cell infiltration levels in HNSCCs and activate mTORC1 signaling pathway in CD4+ T cells. Further analysis from TIDE showed the high expression of CCL17/CCL22 might predict favorable responses to immune checkpoint blockade therapy in HNSCC patients. These findings provide an insight into the predictive roles of CCL17/CCL22 in HNSCC.

OBJECTIVE: Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases remain unexplained, with immunologic and vascular growth alterations being considered as probable causes. Chemokines are produced by a variety of cells and exhibit several functions including both pro and anti-angiogenic properties. In this study, we investigated the role of the angiogenic and angiostatic chemokines in placenta and decidua tissues from spontaneous and induced abortions.
METHODS: Total RNA was extracted from the placenta and decidua tissues, which was then purified and converted into cDNA. Real-time PCR was then performed for the expression of the angiogenic CCL2, CCL5, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8 and CXCL4, and the angiostatic CXCL9, CXCL10, CXCL11, CXCL12 and CXCL14 and results were then statistically analyzed.
RESULTS: Regarding the placenta, CXCL7 (2.29-fold, 2.16-2.38, p < 0.05), CXCL4 (1.01-fold, 0.74-4.447, p < 0.05), CXCL9 (0.87-fold, 0.43-1.34, p < 0.05) and CXCL11 (0.31-fold, 0.22-0.45, p < 0.05) were altered in spontaneous abortions. CCL2, CCL5, CXCL2-3, CXCL8, CXCL10, CXCL12 and CXCL14 were not statistically significant altered. Regarding the decidua, CXCL7 (7.13-fold, 6.32-7.54, p < 0.01), CXCL8 (11.02-fold, 8.58-13.45, p < 0.05), CCL20 (1.21-fold, 0.29-1.89, p < 0.05) and CXCL9 (5.49-fold, 3.67-6.39, p < 0.05) were overexpressed in spontaneous abortions. CXCL2-4, CCL2, CCL5, CXCL10-12 and CXCL14 did not show any differences. The expression of the chemokines CXCL1, CXCL5-6 was absent in either tissue or group.
CONCLUSIONS: Our results show that the overexpression of angiostatic and diminished expression of angiogenic chemokines takes place in the placenta and decidua of spontaneous abortions, suggesting that dysregulation of angiogenesis could be a contributive factor to the pathogenesis of miscarriage.

Experimental studies have revealed the involvement of neuroinflammation mediated by activated microglia in the pathophysiology of depression, suggesting a novel target for treatment. The atypical antidepressant Agomelatine (Ago) has an advantage compared to the classical antidepressants due to its chronobiotic activity and unique pharmacological profile as a selective agonist at the melatonin receptors and an antagonist at the 5HT2C receptors. We have recently revealed that Ago can exert a potent antidepressant effect in rats exposed to a chronic constant light (CCL). In the present study, we hypothesized that the anti-inflammatory activity of this melatonin analog on activated neuroglia in specific brain structures might contribute to its antidepressant effect in this model. Chronic Ago treatment (40 mg/kg, i.p. for 21 days) was executed during the last 3 weeks of a 6-week period of CCL exposure in rats. The CCL-vehicle-treated rats showed a profound neuroinflammation characterized by microgliosis and astrogliosis in the hippocampus, basolateral amygdala (BL) and partly in the piriform cortex (Pir) confirmed by immunohistochemistry. With the exception of the Pir, the CCL regime was accompanied by neuronal damage, identified by Nissl staining, in the hippocampus and basolateral amygdala and impaired neurogenesis with reduced dendritic complexity of hippocampal neuroprogenitor cells detected by doublecortin-positive cells in the dentate gyrus (DG) subgranular zone compared to the control group. Ago reversed the gliosis in a region-specific manner and partially restored the suppressed DG neurogenesis. Ago failed to produce neuroprotection in CCL exposed rats. The present results suggest that the beneficial effects of Ago represent an important mechanism underlying its antidepressant effect in models characterized by impaired circadian rhythms.

The impact of ligands of the 18 kDa translocator protein (TSPO) on the release of chemokines is not vastly investigated. In the present study, we assessed the effect of our novel TSPO ligands 2-Cl-MGV-1 and 2,4-Di-Cl-MGV-1 compared to the classical TSPO ligand PK 11195 on chemokine release in LPS-stimulated BV-2 microglial cells. As per the effect of 2-Cl-MGV-1, CCL2, CCL3, and CCL5 were inhibited by 90%, CCL8 by 97%, and IL-2 by 77% (p < 0.05 for all). 2,4-Di-Cl-MGV-1 inhibited CCL2 release by 92%, CCL3 by 91%, CCL5 by 90%, CCL8 by 89%, and IL-2 by 80% (p < 0.05 for all). PK 11195 exhibited weaker inhibitory effects: CCL2 by 22%, CCL3 by 83%, CCL5 by 34%, CCL8 by 41%, and the cytokine IL-2 by 14% (p < 0.05 for all). Thus, it appears that the novel TSPO ligands are potent suppressors of LPS-stimulated BV-2 microglial cells, and their inhibitory effect is larger than that of PK 11195. Such immunomodulatory effects on microglial cells may be relevant to the treatment of neurodegenerative and neuroinflammatory diseases.