BACKGROUND: Major depressive disorder (MDD) is a common and debilitating mental illness characterized by persistent feelings of sadness, hopelessness, and a lack of interest in daily activities. The objective of this study was to investigate whether levels of macrophage inflammatory protein-1β (MIP-1β) and macrophage chemoattractant protein-2 (MCP-2) in the blood were associated with the pathophysiology and development of MDD compared to healthy controls (HCs).
METHODS: This case-control study was conducted involving 50 MDD patients and 38 HCs. We performed a comprehensive assessment to match age, sex, BMI, and socio-demographic profile between the groups. The study excluded participants with chronic infection, inflammatory diseases, coexisting psychiatric disorder, history of liver and kidney diseases, and individuals who are under antipsychotic medications. A professional psychiatrist diagnosed MDD patients and evaluated HCs based on the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria. The severity of depression was assessed using the Hamilton Depression (Ham-D) rating scale. Commercially available enzyme-linked immunosorbent assay (ELISA) kits were used to quantify the serum MIP-1β and MCP-2 levels.
RESULTS: The results indicated elevated serum MIP-1β levels (207.73±24.24 pg/ml) in MDD patients compared to HCs (58.77±9.14 pg/ml). This difference in concentration is positively correlated with severity of disease symptoms (r = 0.451; p<0.001). Similarly, the levels of MCP-2 were found to be elevated in patients compared to controls (143.61±19.92 vs. 56.84±4.02 pg/ml; p = 0.003), with a positive correlation with the Ham-D scores (r = 0.373; p = 0.004).
CONCLUSIONS: According to this study, elevated levels of MIP-1β and MCP-2 may be associated with the pathophysiology and development of MDD. These increased serum MIP-1β and MCP-2 levels could be used as risk assessment tools for MDD. The present findings urge further research and the development of therapeutic and diagnostic approaches for depression.

The purpose of this study is to investigate the serum inflammatory factors in patients with high-altitude polycythemia (HAPC) and their correlation with cognitive function. The subjects were recruited and placed into a HAPC group and control group. Serum samples were collected, and inflammatory factors (interleukin-1beta [IL-1β], monocyte chemoattractant protein-1 [MCP-1], and tumor necrosis factor-alpha [TNF-α]) were measured using ELISA kits. The mini-mental State Examination (MMSE) was used to assess cognitive function. According to the MMSE scores, HAPC group was further divided into normal cognitive function group (HNCF) and cognitive dysfunction group (HCDF). In comparison with the control group, the MMSE scores in the HAPC group were significantly low (P < .05), whereas the serum levels of IL-1β, MCP-1, and TNF-α were significantly high (P < .01). Among the HAPC group (n = 60), 21 belonged to the HCDF and 39 belonged to the HNCF. Compared with the HNCF, the IL-1β, MCP-1, and TNF-α in the HCDF were significantly increased (P < .01). The Pearson correlation analysis showed that inflammatory factors were positively correlated with hemoglobin, and negatively correlated with MMSE. Serum inflammatory cytokines IL-1, MCP-1, and TNF-α were increased in HAPC, and HAPC exhibited cognitive dysfunction. Considering chronic hypoxia environment influences the change of the red blood cell metabolic and inflammatory factor, red blood cells and inflammatory factor in plateau is likely to be affected by patients with vascular lesions, increase cognitive impairment.

OBJECTIVE: To study the association of pro-inflammatory markers with incident diabetes in India.
METHODS: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use.
RESULTS: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55]).
CONCLUSIONS: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

The MCP-1/CCR2 axis is one of the major chemokine signaling pathways that play a crucial role in the tumor microenvironment and has been involved in triggering various tumor progression mechanisms, such as increasing the immunosuppressive cells recruitment and promoting tumor cell proliferation and invasiveness.
The current study investigated the association of MCP1 (rs1024611) and CCR2 (rs1799864) genes variants with the risk as well as prognosis of colorectal cancer (CRC) and colorectal liver metastases (CRLM).
A retrospective cohort study involved 408 patients (284 CRC and 124 CRLM), and 284 healthy control was conducted. Genotyping of selected polymorphisms was performed by PCR-RFLP assays and confirmed by microchip and capillary electrophoresis.
The results highlighted a positive association between MCP1 rs1024611 (non-AA) and CCR2 rs1799864 (GA) genotypes with increased CRC and CRLM risk. Correlation between SNPs and clinicopathological characteristics revealed a positive association between MCP1 rs1024611 and CCR2 rs1799864 (dominant model) and CRC poor prognosis features. Kaplan-Meier survival analysis revealed a significant association between MCP1 rs1024611 non-AA carriers and decreased survival rate. Neoadjuvant treatment showed an improvement in CRC and CRLM survival rates among carriers of MCP1 and CCR2 wild-type genotype. FOLFIRI chemotherapy exhibits reduced survival rates for patients who carried mutated genotypes of MCP1 and CCR2 polymorphisms.
Considering our results, we suggest That both MCP1 and CCR2 polymorphisms may constitute independent factors for CRC and CRLM occurrence and can be helpful targets for an efficient therapeutic approach.

As a result of SARS-CoV-2 infection, the host\'s immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables. Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.
目的： 分析趋化因子单核细胞趋化蛋白-1（MCP1）基因多态性、循环水平与乳腺癌的关联性。 方法： 采用病例对照研究设计，纳入820例病理学诊断为乳腺癌的患者为病例组，同期到医院进行常规健康体检的年龄和居住地与病例组匹配的900名健康者为对照组。孟德尔随机化分析采用三个广泛关注的MCP1基因功能性单核苷酸多态性（SNP）位点rs1024611、rs2857656和rs4586构建工具变量，分析趋化因子MCP1循环水平与乳腺癌的关联性。 结果： MCP1 rs1024611（OR=1.26，P=0.002）、rs2857656（OR=1.23，P=0.006）和rs4586（OR=1.23，P=0.003）与乳腺癌风险增加显著相关。SNP rs1024611（β=1.194，P<0.001）、rs2857656（β=1.221，P<0.001）和rs4586（β=1.137，P<0.001）的罕见等位基因与MCP1循环水平呈正相关。病例对照研究显示，MCP1循环水平每增加23.7 pg/ml，乳腺癌风险增加0.25倍；MR分析显示，MCP1循环水平的每增加23.7 pg/ml，乳腺癌风险增加0.20倍。 结论： MCP1基因多态性与乳腺癌风险增加显著相关，MCP1循环水平升高增加乳腺癌的发病风险，MCP1可作为乳腺癌早期预测的生物学标志物。.

Type 2 diabetes (T2D) and its secondary complications result from the complex interplay of genetic and environmental factors. To understand the role of these factors on disease susceptibility, the present study was conducted to assess the association of eNOS and MCP-1 variants with T2D and diabetic nephropathy (DN) in two ethnically and geographically different cohorts from North India. A total of 1313 subjects from two cohorts were genotyped for eNOS (rs2070744, rs869109213 and rs1799983) and MCP-1 (rs1024611 and rs3917887) variants. Cohort-I (Punjab) comprised 461 T2D cases (204 T2D with DN and 257 T2D without DN) and 315 healthy controls. Cohort-II (Jammu and Kashmir) included 337 T2D (150 T2D with DN and 187 T2D without DN) and 200 controls. Allele, genotype and haplotype frequencies were compared among the studied participants, and phenotype-genotype interactions were determined. Meta-analysis was performed to investigate the association between the selected variants and disease susceptibility. All three eNOS variants were associated with 1.5-4.0-fold risk of DN in both cohorts. MCP-1 rs1024611 conferred twofold risk towards DN progression in cohort-II, while rs3917887 provided twofold risk for both T2D and DN in both cohorts. eNOS and MCP-1 haplotypes conferred risk for T2D and DN susceptibility. Phenotype-genotype interactions showed significant associations between the studied variants and anthropometric and biochemical parameters. In meta-analysis, all eNOS variants conferred risk towards DN progression, whereas no significant association was observed for MCP-1 rs1024611. We show evidences for an association of eNOS and MCP-1 variants with T2D and DN susceptibility.

Monocyte chemoattractant protein-1 (MCP-1) is reported to associate with the severity and development of Alzheimer\'s disease (AD). While a few studies have examined the association between the MCP-1 A-2518 G polymorphism and AD risk, no Chinese study has undertaken a study of this association. Therefore, a case-control study with 212 AD cases and 268 controls was designed in Chinese participants. Logistic regression analysis was utilized to probe the potential link between AD susceptibility and the MCP-1 A-2518 G polymorphism. We observed that the GG or GG + AG genotype was shown to elevate the risk of AD. Subgroup analysis revealed this increased risk effect was also presented in males, smokers, APOE ε4+ and those participants ≥ 65 years old. Notably, cross-over analysis found that this polymorphism interacted with smoking, contributing to the increased risk of AD. In addition, we found that the serum MCP-1 levels of AD patients were evidently higher than in controls. Furthermore, the MCP-1 A-2518 G polymorphism was linked with the serum MCP-1 levels of AD patients, but not controls. In conclusion, the MCP-1 A-2518 G polymorphism correlates with an elevated risk of AD and increased MCP-1 serum levels. The interaction between the MCP-1 A-2518 G polymorphism and smoking contributes to the increased risk for AD in Chinese Han individuals.

The serum amyloid A (SAA) gene family is highly conserved and encodes acute phase proteins that are upregulated in response to inflammatory triggers. Over the years, a considerable amount of literature has been published attributing a wide range of biological effects to SAAs such as leukocyte recruitment, cytokine and chemokine expression and induction of matrix metalloproteinases. Furthermore, SAAs have also been linked to protumorigenic, proatherogenic and anti-inflammatory effects. Here, we investigated the biological effects conveyed by murine SAA3 (mu rSAA3) recombinantly expressed in Escherichia coli. We observed the upregulation of a number of chemokines including CCL2, CCL3, CXCL1, CXCL2, CXCL6 or CXCL8 following stimulation of monocytic, fibroblastoid and peritoneal cells with mu rSAA3. Furthermore, this SAA variant displayed potent in vivo recruitment of neutrophils through the activation of TLR4. However, a major problem associated with proteins derived from recombinant expression in bacteria is potential contamination with various bacterial products, such as lipopolysaccharide, lipoproteins and formylated peptides. This is of particular relevance in the case of SAA as there currently exists a discrepancy in biological activity between SAA derived from recombinant expression and that of an endogenous source, i.e. inflammatory plasma. Therefore, we subjected commercial recombinant mu rSAA3 to purification to homogeneity via reversed-phase high-performance liquid chromatography (RP-HPLC) and re-assessed its biological potential. RP-HPLC-purified mu rSAA3 did not induce chemokines and lacked in vivo neutrophil chemotactic activity, but retained the capacity to synergize with CXCL8 in the activation of neutrophils. In conclusion, experimental results obtained when using proteins recombinantly expressed in bacteria should always be interpreted with care.

Monocyte chemoattractant protein 1 (MCP-1) plays an important role in the development of periodontitis. The purpose of this investigation was to evaluate association of the  MCP-1 gene polymorphism with chronic periodontitis in patients with end-stage renal disease (ESRD). One hundred fifty ESRD patients with chronic periodontitis (CP), 100 without CP and 190 healthy controls were included in this study. Genomic DNA from all participants was genotyped for the -2518 (A/G) polymorphism by a polymerase chain reaction - restriction fragment length polymorphism (PCR--RFLP) assay. Significant differences were observed in the genotype and allele frequencies between patients with ESRD and CP and controls.  The G allele frequency was significantly higher in patients than in control subjects, with odds ratio 1.77 (95 % CI 1.2-2.5), p = 0.0014. For the GG genotype the OR was 3.63 (95 % CI 1.5-8.76), p = 0.041.  No significant differences in the polymorphism distribution were observed between ESRD patients  without CP and control subjects. Comparison of the MCP-1 gene polymorphism distribution in ESRD patients with various primary diseases leading to ESRD did not show any significant differences. The mean MCP-1 serum levels were compared between subgroups. They were significantly higher in ESRD patients with CP (582 ± 112 pg/ml) than in patients without CP (309 ± 103 pg/ml) and controls (265 ± 85 pg/ml). Our results suggest that the MCP-1-2518 A/G  polymorphism might be a novel risk factor for developing chronic periodontitis in patients with ESRD.