Upregulation of EMR1 (ADGRE1) by Tumor-Associated Macrophages Promotes Colon Cancer Progression by Activating the JAK2/STAT1,3 Signaling Pathway in Tumor Cells.

Previously, we reported that epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR1/ADGRE1) is abnormally expressed in colon cancer (CC) and is a risk factor for lymph node metastasis (LNM) and poor recurrence-free survival in patients with abundant tumor-associated macrophages (TAMs). However, the signaling pathways associated with EMR1 expression in CC progression remain unclear. In this study, we aimed to explore the role of EMR1 and its signaling interactions with macrophages in CC progression. Spatial transcriptomics of pT3 microsatellite unstable CC tissues revealed heightened Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in EMR1-HL CC with LNM compared to EMR1-N CC without LNM. Through in vitro coculture of CC cells with macrophages, EMR1 expression by CC cells was found to be induced by TAMs, ultimately interacting with upregulated JAK/STAT signaling, increasing cell proliferation, migration, and motility, and reducing apoptosis. JAK2/STAT3 inhibition decreased the levels of EMR1, JAK2, STAT1, and STAT3, significantly impeded the proliferation, migration, and mobility of cells, and increased the apoptosis of EMR1+ CC cells compared to their EMR1KO counterparts. Overall, TAMs-induced EMR1 upregulation in CC cells may promote LNM and CC progression via JAK2/STAT1,3 signaling upregulation. This study provides further insights into the molecular mechanisms involving macrophages and intracellular EMR1 expression in CC progression, suggesting its clinical significance and offering potential interventions to enhance patient outcomes.

RETRACTED: Akter et al. Potential Role of Natural Products to Combat Radiotherapy and Their Future Perspectives. Molecules 2021, 26, 5997.

This published review [...].

A Prospective Viewpoint on Neurological Diseases and Their Biomarkers.

Neurodegenerative diseases (NDDs) are disorders that affect both the central and peripheral nervous systems. To name a few causes, NDDs can be caused by ischemia, oxidative and endoplasmic reticulum (ER) cell stress, inflammation, abnormal protein deposition in neural tissue, autoimmune-mediated neuron loss, and viral or prion infections. These conditions include Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson's disease (PD). The formation of ß-sheet-rich aggregates of intra- or extracellular proteins in the CNS hallmarks all neurodegenerative proteinopathies. In systemic lupus erythematosus (SLE), numerous organs, including the central nervous system (CNS), are affected. However, the inflammatory process is linked to several neurodegenerative pathways that are linked to depression because of NDDs. Pro-inflammatory signals activated by aging may increase vulnerability to neuropsychiatric disorders. Viruses may increase macrophages and CCR5+ T cells within the CNS during dementia formation and progression. Unlike medical symptoms, which are just signs of a patient's health as expressed and perceived, biomarkers are reproducible and quantitative. Therefore, this current review will highlight and summarize the neurological disorders and their biomarkers.

Involvement of Resveratrol against Brain Cancer: A Combination Strategy with a Pharmaceutical Approach.

A brain tumor (BT) is a condition in which there is growth or uncontrolled development of the brain cells, which usually goes unrecognized or is diagnosed at the later stages. Since the mechanism behind BT is not clear, and the various physiological conditions are difficult to diagnose, the success rate of BT is not very high. This is the central issue faced during drug development and clinical trials with almost all types of neurodegenerative disorders. In the first part of this review, we focus on the concept of brain tumors, their barriers, and the types of delivery possible to target the brain cells. Although various treatment methods are available, they all have side effects or toxic effects. Hence, in the second part, a correlation was made between the use of resveratrol, a potent antioxidant, and its advantages for brain diseases. The relationship between brain disease and the blood-brain barrier, multi-drug resistance, and the use of nanomedicine for treating brain disorders is also mentioned. In short, a hypothetical concept is given with a background investigation into the use of combination therapy with resveratrol as an active ingredient, the possible drug delivery, and its formulation-based approach.

Climate variability, socio-ecological factors and dengue transmission in tropical Queensland, Australia: A Bayesian spatial analysis.

BACKGROUND: Dengue is a wide-spread mosquito-borne disease globally with a likelihood of becoming endemic in tropical Queensland, Australia. The aim of this study was to analyse the spatial variation of dengue notifications in relation to climate variability and socio-ecological factors in the tropical climate zone of Queensland, Australia. METHODS: Data on the number of dengue cases and climate variables including minimum temperature, maximum temperature and rainfall for the period of January 1st, 2010 to December 31st, 2015 were obtained for each Statistical Local Area (SLA) from Queensland Health and Australian Bureau of Meteorology, respectively. Socio-ecological data including estimated resident population, percentage of Indigenous population, housing structure (specifically terrace house), socio-economic index and land use types for each SLA were obtained from Australian Bureau of Statistics, and Australian Bureau of Agricultural and Resource Economics and Sciences, respectively. To quantify the relationship between dengue, climate and socio-ecological factors, multivariate Poisson regression models in a Bayesian framework were developed with a conditional autoregressive prior structure. Posterior parameters were estimated using Bayesian Markov Chain Monte Carlo simulation with Gibbs sampling. RESULTS: In the tropical climate zone of Queensland, the estimated number of dengue cases was predicted to increase by 85% [95% Credible Interval (CrI): 25%, 186%] and 7% (95% CrI: 0.1%, 14%) for a 1-mm increase in average annual rainfall and 1% increase in the proportion of terrace houses, respectively. The estimated spatial variation (structured random effects) was small compared to the remaining unstructured variation, suggesting that the inclusion of covariates resulted in no residual spatial autocorrelation in dengue data. CONCLUSIONS: Climate and socio-ecological factors explained much of the heterogeneity of dengue transmission dynamics in the tropical climate zone of Queensland. Results will help to further understand the risk factors of dengue transmission and will provide scientific evidence in designing effective local dengue control programs in the most needed areas.

Potential Role of Natural Products to Combat Radiotherapy and Their Future Perspectives.

Cancer is the second leading cause of death in the world. Chemotherapy and radiotherapy (RT) are the common cancer treatments. In addition to these limitations, the development of adverse effects from chemotherapy and RT reduces the quality of life for cancer patients. Cellular radiosensitivity, or the ability to resist and overcome cell damage caused by ionizing radiation (IR), is directly related to cancer cells' response to RT. Therefore, radiobiological research is emphasizing chemical compounds 'radiosensitization of cancer cells so that they are more reactive in the IR spectrum. Recent years researchers have seen an increase in interest in natural products that have antitumor effects with minimal side effects. Natural products, on the other hand, are easy to recover and therefore less expensive. There have been several scientific studies done based on these compounds that have tested their ability in vitro and in vivo to induce tumor radiosensitization. The role of natural products in RT, as well as their usefulness and potential applications, is the goal of this current review.

Chemo-Preventive Action of Resveratrol: Suppression of p53-A Molecular Targeting Approach.

Extensive experimental, clinical, and epidemiological evidence has explained and proven that products of natural origin are significantly important in preventing and/or ameliorating various disorders, including different types of cancer that researchers are extremely focused on. Among these studies on natural active substances, one can distinguish the emphasis on resveratrol and its properties, especially the potential anticancer role. Resveratrol is a natural product proven for its therapeutic activity, with remarkable anti-inflammatory properties. Various other benefits/actions have also been reported, such as cardioprotective, anti-ageing, antioxidant, etc. and its rapid digestion/absorption as well. This review aims to collect and present the latest published studies on resveratrol and its impact on cancer prevention, molecular signals (especially p53 protein participation), and its therapeutic prospects. The most recent information regarding the healing action of resveratrol is presented and concentrated to create an updated database focused on this topic presented above.

Therapeutic Potential of Natural Products in Treating Neurodegenerative Disorders and Their Future Prospects and Challenges.

Natural products derived from plants, as well as their bioactive compounds, have been extensively studied in recent years for their therapeutic potential in a variety of neurodegenerative diseases (NDs), including Alzheimer's (AD), Huntington's (HD), and Parkinson's (PD) disease. These diseases are characterized by progressive dysfunction and loss of neuronal structure and function. There has been little progress in designing efficient treatments, despite impressive breakthroughs in our understanding of NDs. In the prevention and therapy of NDs, the use of natural products may provide great potential opportunities; however, many clinical issues have emerged regarding their use, primarily based on the lack of scientific support or proof of their effectiveness and patient safety. Since neurodegeneration is associated with a myriad of pathological processes, targeting multi-mechanisms of action and neuroprotection approaches that include preventing cell death and restoring the function of damaged neurons should be employed. In the treatment of NDs, including AD and PD, natural products have emerged as potential neuroprotective agents. This current review will highlight the therapeutic potential of numerous natural products and their bioactive compounds thatexert neuroprotective effects on the pathologies of NDs.

Impacting the Remedial Potential of Nano Delivery-Based Flavonoids for Breast Cancer Treatment.

Breast cancer persists as a diffuse source of cancer despite persistent detection and treatment. Flavonoids, a type of polyphenol, appear to be a productive option in the treatment of breast cancer, because of their capacity to regulate the tumor related functions of class of compounds. Plant polyphenols are flavonoids that appear to exhibit properties which are beneficial for breast cancer therapy. Numerous epidemiologic studies have been performed on the dynamic effect of plant polyphenols in the prevention of breast cancer. There are also subclasses of flavonoids that have antioxidant and anticarcinogenic activity. These can regulate the scavenging activity of reactive oxygen species (ROS) which help in cell cycle arrest and suppress the uncontrolled division of cancer cells. Numerous studies have also been performed at the population level, one of which reported a connection between cancer risk and intake of dietary flavonoids. Breast cancer appears to show intertumoral heterogeneity with estrogen receptor positive and negative cells. This review describes breast cancer, its various factors, and the function of flavonoids in the prevention and treatment of breast cancer, namely, how flavonoids and their subtypes are used in treatment. This review proposes that cancer risk can be reduced, and that cancer can be even cured by improving dietary intake. A large number of studies also suggested that the intake of fruit and vegetables is associated with reduced breast cancer and paper also includes the role and the use of nanodelivery of flavonoids in the healing of breast cancer. In addition, the therapeutic potential of orally administered phyto-bioactive compounds (PBCs) is narrowed because of poor stability and oral bioavailability of compounds in the gastrointestinal tract (GIT), and solubility also affects bioavailability. In recent years, creative nanotechnology-based approaches have been advised to enhance the activity of PBCs. Nanotechnology also offers the potential to become aware of disease at earlier stages, such as the detection of hidden or unconcealed metastasis colonies in patients diagnosed with lung, colon, prostate, ovarian, and breast cancer. However, nanoformulation-related effects and safety must not be overlooked. This review gives a brief discussion of nanoformulations and the effect of nanotechnology on herbal drugs.

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets.

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.

Different responses of dengue to weather variability across climate zones in Queensland, Australia.

BACKGROUND: Dengue is a significant public health concern in northern Queensland, Australia. This study compared the epidemic features of dengue transmission among different climate zones and explored the threshold of weather variability for climate zones in relation to dengue in Queensland, Australia. METHODS: Daily data on dengue cases and weather variables including minimum temperature, maximum temperature and rainfall for the period of January 1, 2010 to December 31, 2015 were obtained from Queensland Health and Australian Bureau of Meteorology, respectively. Climate zones shape file for Australia was also obtained from Australian Bureau of Meteorology. Kruskal-Wallis test was performed to check whether the distribution of dengue significantly differed between climate zones. Time series regression tree model was used to estimate the threshold effects of the monthly weather variables on dengue in different climate zones. RESULTS: During the study period, the highest dengue incidence rate was found in the tropical climate zone (15.09/10,000) with the second highest in the grassland climate zone (3.49/10,000). Dengue responded differently to weather variability in different climate zones. In every climate zone, temperature was the primary predictor of dengue. However, the threshold values, type of temperature (e.g. maximum, minimum, or mean), and lag time for dengue varied between climate zones. Monthly mean temperature above 27°C at a lag of two months and monthly minimum temperature above 22°C at a lag of one month was found to be the most favourable weather condition for dengue in the tropical and subtropical climate zone, respectively. However, in the grassland climate zone, maximum temperature above 38°C at a lag of five months was found to be the ideal condition for dengue. Monthly rainfall with threshold value of 1.7 mm was found to be a significant contributor to dengue only in the tropical climate zone. CONCLUSIONS: The temperature threshold for dengue was lower in both tropical and subtropical climate zones than in the grassland climate zone. The different temperature threshold between climate zones suggests that an early warning system would need to be developed based on local socio-ecological conditions of the climate zone to manage dengue control and intervention programs effectively.

M1 Macrophages Promote TRAIL Expression in Adipose Tissue-Derived Stem Cells, Which Suppresses Colitis-Associated Colon Cancer by Increasing Apoptosis of CD133+ Cancer Stem Cells and Decreasing M2 Macrophage Population.

We have previously reported that adipose tissue-derived stem cells (ASCs) cultured at high cell density can induce cancer cell death through the expression of type I interferons and tumor necrosis factor (TNF)-related apoptosis-inducing ligands (TRAIL). Here, we investigated whether TRAIL-expressing ASCs induced by M1 macrophages can alleviate colitis-associated cancer in an azoxymethane (AOM)/dextran sodium sulfate (DSS) animal model. M1 macrophages significantly increased the TRAIL expression in ASCs, which induced the apoptosis of LoVo cells in a TRAIL-dependent manner. However, CD133knockout LoVo cells, generated using the CRISPR-Cas9 gene-editing system, were resistant to TRAIL. In the AOM/DSS-induced colitis-associated cancer model, the intraperitoneal transplantation of TRAIL-expressing ASCs significantly suppressed colon cancer development. Moreover, immunohistochemical staining revealed a low CD133 expression in tumors from the AOM/DSS + ASCs group when compared with tumors from the untreated group. Additionally, the ASC treatment selectively reduced the number of M2 macrophages in tumoral (45.7 ± 4.2) and non-tumoral mucosa (30.3 ± 1.5) in AOM/DSS + ASCs-treated animals relative to those in the untreated group (tumor 71.7 ± 11.2, non-tumor 94.3 ± 12.5; p < 0.001). Thus, TRAIL-expressing ASCs are promising agents for anti-tumor therapy, particularly to alleviate colon cancer by inducing the apoptosis of CD133+ cancer stem cells and decreasing the M2 macrophage population.

Joint effects of climate variability and socioecological factors on dengue transmission: epidemiological evidence.

OBJECTIVE: To assess the epidemiological evidence on the joint effects of climate variability and socioecological factors on dengue transmission. METHODS: Following PRISMA guidelines, a detailed literature search was conducted in PubMed, Web of Science and Scopus. Peer-reviewed, freely available and full-text articles, considering both climate and socioecological factors in relation to dengue, published in English from January 1993 to October 2015 were included in this review. RESULTS: Twenty studies have met the inclusion criteria and assessed the impact of both climatic and socioecological factors on dengue dynamics. Among those, four studies have further investigated the relative importance of climate variability and socioecological factors on dengue transmission. A few studies also developed predictive models including both climatic and socioecological factors. CONCLUSIONS: Due to insufficient data, methodological issues and contextual variability of the studies, it is hard to draw conclusion on the joint effects of climate variability and socioecological factors on dengue transmission. Future research should take into account socioecological factors in combination with climate variables for a better understanding of the complex nature of dengue transmission as well as for improving the predictive capability of dengue forecasting models, to develop effective and reliable early warning systems.

Unveiling the Potential of Polyphenols as Anti-Amyloid Molecules in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aß) cascade is the dominant hypothesis. According to the Aß hypothesis, a progressive buildup of extracellular and intracellular Aß aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aß plays an important role in the etiology of AD, therefore Aß-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aß plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aß (a peptide of 39-42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aß aggregation and prevent the formation of Aß oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aß in AD pathogenesis, the Aß aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.

Multifaceted Effects of Intermittent Fasting on the Treatment and Prevention of Diabetes, Cancer, Obesity or Other Chronic Diseases.

BACKGROUND: Obesity and diabetes are global epidemics resulting in a range of comorbidities. Both have been linked to an increased risk of hormonal imbalance, cancer, and other significant disorders, which are a concerning trend for cancer rates in the backdrop of rising obesity and diabetes rates worldwide. Around 1 in 10 persons in the United States and Canada have serious illnesses correlated to type 2 diabetes and early death. It is believed that the US economy alone spends $245 billion annually due to this health burden. Lifestyle modification with intermittent fasting protocol and proper diet helps lower blood glucose level, maintain the body mass index, and reduce inflammation, which is the main cause of all chronic diseases. METHODS: We searched case series and clinical trials on type 2 diabetes, insulin resistance, cancer, thyroid, cardiovascular disease, or other inflammatory diseases in response to intermittent fasting in the PubMed, MEDLINE, and Google Scholar databases. OBJECTIVE: In this review, we have focused on intermittent fasting-based approaches that are becoming more widely accepted for improving health and reducing unwanted effects in patients with type 2 diabetes, cancer, cardiovascular disease, neurodegenerative disease, obesity, thyroid, and hormonal imbalance; it is also contemplated whether intermittent fasting can be considered as a non-medicinal therapeutic option for persons suffering from chronic diseases. CONCLUSION: Intermittent fasting successfully reversed diabetes, thyroid, and high blood pressure, elevated lipid levels, and maintained the body mass index; also, studies have shown that it has been instructed to be followed for the treatment and prevention of cancer and neurodegenerative diseases.

Therapeutic Approaches for the Management of Autoimmune Disorders via Gene Therapy: Prospects, Challenges and Opportunities.

BACKGROUND: Autoimmune diseases are the diseases that result due to the overactive immune response, and comprehend systemic autoimmune diseases like Rheumatoid Arthritis (RA), SjÓ§gren's Syndrome (SS), and organ-specific autoimmune diseases like type-1 diabetes mellitus (T1DM), Myasthenia Gravis (MG), and Inflammatory Bowel Disease (IBD). Currently, there is no long-term cure; but, several treatments exist which retard the evolution of the disease, embracing gene therapy, which has been scrutinized to hold immense aptitude for the management of autoimmune diseases. OBJECTIVE: The review highlights the pathogenic mechanisms and genes liable for the development of autoimmune diseases, namely T1DM, type-2 diabetes mellitus (T2DM), RA, SS, IBD, and MG. Furthermore, the review focuses on investigating the outcomes of delivering the corrective genes with their specific viral vectors in various animal models experiencing these diseases to determine the effectiveness of gene therapy. METHODS: Numerous review and research articles emphasizing the tremendous potential of gene therapy in the management of autoimmune diseases were procured from PubMed, MEDLINE, Frontier, and other databases and thoroughly studied for writing this review article. RESULTS: The various animal models that experienced treatment with gene therapy have displayed regulation in the levels of proinflammatory cytokines, infiltration of lymphocytes, manifestations associated with autoimmune diseases, and maintained equilibrium in the immune response, thereby compete with the progression of autoimmune diseases. CONCLUSION: Gene therapy has revealed prodigious aptitude in the management of autoimmune diseases in various animal studies, but further investigation is essential to combat the limitations associated with it and before employing it on humans.

A Comprehensive Review on Hydrogels.

The conventional drug delivery systems have a long list of repeated dosing and toxicity issues. The hydrogels solve these issues as they minimize such activities and optimize therapeutic benefits. The hydrogels possess tunable properties that can withstand degradation, metabolism, and control release moieties. Some areas of applications of hydrogels involve wound healing, ocular systems, vaginal gels, scaffolds for tissue and bone engineering, etc. They comprise about 90% of the water that makes them suitable bio-mimic moiety. Here, we present an extensive review of various perspectives of hydrogels, along with their applications.

5-Fluorouracil and Curcumin Combination Coated with Pectin and Its Strategy towards Titanium Dioxide, Dimethylhydrazine Colorectal Cancer Model with the Evaluation of the Blood Parameters.

Colorectal cancer is considered the third most common cancer and the second leading cause of death globally. It has been proven that titanium dioxide nanoparticles produce oxidative stress and can lead to chronic inflammation, which could turn into diseases like cancer, cardiovascular disorders, diabetes, and so on. To evaluate the effect of 5-fluorouracil (5-FU) curcumin (CUR) conjugate coated with pectin on colorectal cancer induced by titanium dioxide nanoparticles (TiO2-NPs) and dimethylhydrazine (DMH), male rats were administered TiO2-NPs (5 mg/kg) orally and DMH (1 mg/kg) peritoneally for 70 days and treated with 5-FU (60 mg/kg) and CUR (240 mg/kg) conjugate (1:4 ratio) coated with pectin. The bodyweight of the animals was evaluated, and the blood sugar level was calculated. Further blood and plasma analyses were conducted. Hematological parameters, antioxidant parameters, and biochemical estimation were taken into consideration. The TiO2-NPs level in the blood and colorectal region was also calculated. With the induction of colon cancer using TiO2-NPs and DMH, a significant increase in the body weight of the animals was seen; eventually, with treatment, it was reduced. The bodyweight increase was due to an increase in the blood sugar level. There were also significant changes in the hematological parameters and biochemical estimation reports when comparing those of the positive control, negative control, and treated groups. No significant effect on biochemical estimation reports was seen. Conclusions: These reports suggest that 5-FU CUR conjugate coated with pectin helps in the management of colorectal cancer induced by TiO2-NPs and DMH.

A Background Search on the Potential Role of Scutellaria and Its Essential Oils.

Scutellaria (Lamiaceae), which contains over 350 species, usually known as skullcaps, is found throughout Europe, the United States, and East Asia. In traditional Chinese medicine, several species are used to wipe out heat-evil and remove surface ills (TCM). The current study examines the ethnopharmacology, biological activity, and chemical substances associated with Scutellaria species. More than 295 chemicals, including flavonoids and diterpenes, have been identified. Scutellaria and its active principles have been shown in studies to have a wide range of pharmacological activities, including antioxidant, antimicrobial, antifeedant, phytotoxic, acaricidal toxicity, antibacterial, anti-inflammatory, and antianalgesic activities. Currently, effective monomeric compounds or active components from Scutellaria have been evaluated for pharmacological action in vivo and in vitro. More data facilitates applications and exploitation of novel medication development.

EMR1/ADGRE1 Expression in Cancer Cells Upregulated by Tumor-Associated Macrophages Is Related to Poor Prognosis in Colorectal Cancer.

EMR1, a member of the adhesion G protein-coupled receptor family (ADGRE1), is a macrophage marker that is abnormally expressed in cancer cells. However, its clinical significance in colorectal cancer (CRC) is not well-known. In this investigation, EMR1 expression in tumor cells (EMR1-TC) was found in 91 (22.8%) of the 399 CRC samples tested by immunohistochemical staining and showed a significant relationship with lymph node metastasis. Furthermore, EMR1-TC was significantly associated with CD68+ CD163+ tumor-associated macrophages (TAMs), and CRC with a high combined EMR1-TC+CD68+CD163+ score showed worse recurrence-free survival prognosis. In an in vitro co-culture assay of colon cancer cells with myeloid cells, we found that EMR1 expression significantly upregulated in cancer cells was induced by macrophages. In addition, there was increased expression of M2 markers (CD163 and interleukin-6 & 10) in myeloid portion, while that of M1 markers (CD86 and iNOS) remained unchanged. Accordingly, upon treatment with M2 macrophage polarization inhibitors (O-ATP, trametinib, bardoxolone methyl), EMR1 expression reduced significantly, along with M2 markers (CD163 and interleukin-6 & 10). In conclusion, EMR1-TC was a high-risk factor for lymph node metastasis and correlated with poor recurrence free survival, particularly in patients with TAM-rich CRC. Furthermore, EMR1 expression in colon cancer cells may be related to M2 macrophage polarization and vice versa.