Cholestasis is a condition defined as an abnormal decrease of bile flow due to progressive pathological states or cholestatic liver diseases that affect the biliary tree at intrahepatic and extrahepatic level. It induces complications such as cirrhosis, liver failure, malignancies, pruritus, fatigue, bone disease and nutritional deficiencies that merit close follow-up and specific interventions to improve quality of life. Furthermore, cholestasis can progress to end-stage liver disease and represents an entity with high morbidity and mortality; and economic burden, Therefore, it is important that clinicians understand the treatment options for cholestatic liver diseases. This review addresses the pathophysiology of cholangiopathies, a general view of current treatments and their molecular targets, and a specific review of those groups of drugs. The objective is to provide clinicians with an overview of the current treatment of cholangiopathies based on evidence on its efficacy and safety.

In the United States (US), tianeptine is sold as a dietary supplement under the trade name Tianaa™. Tianeptine is a synthetic drug prescribed by physicians as an antidepressant in parts of Europe, Asia and South America. The drug is not permitted for use by physicians in the US, be-cause it is a μ-opioid receptor agonist with a propensity for severe addiction. As incidence of Tianaa™ related opioid addiction across the southern US escalate, the current study aimed to quantify tianeptine in over the counter Tianaa™ White, Red, and Green products. The results of this investigation measured tianeptine levels between 3.1 to 10.9 mg per 531 mg capsules. Tianaa™ White capsules consistently contained the least tianeptine, while Green had the most. Close inspection of Tianaa™ products showed that capsule mass varied by as much as 16% from label claim, and the amount of tianeptine per capsule varied by as much as 35 % from the aver-age measured amount for each product. Tianaa™ Red contains kava leaf extract, which led to the identification of four kavapyrone components by mass spectrometry. The data presented pro-vide insight into tianeptine quantity and capsule mass variation for Tianaa™ supplements sold to customers naive to the risk of addiction.

Tumor necrosis factor receptor 2 or TNFR2 is considered as an appealing target protein due its limited frequency to Tregs which are highly immunosuppressive and its presence on human malignancies. Numerous studies have revealed that TNFR2 is primarily found on MDSCs (myeloid derived suppressor cells) and CD⁺Foxp3⁺ regulatory T cell (Tregs). It has a great importance in the proliferation and functional activity of Tregs and MDSCs. To treat malignancies and diseases like autoimmune disorder, the suppressor activity of TNFR2 must be eliminated by downregulation or upregulation. Therefore, at the molecular level, advances in comprehension of TNFR2's complex structure and its binding to TNF have opened the door to structure-guided drug development. Two key obstacles of cancer treatment are the dearth of Treg-specific inhibitors and the lack of widely applicable ways to directly target tumors via frequently expressed surface oncogenes. Many researchers have discovered potential antagonist and agonist of TNFR2 which were successful in the inhibition of Tregs proliferation, reduction of soluble TNFR2 secretion from normal cells and in the expansion of T effector cells. The representation of the data in the following review article elucidates the clinically administrated TNFR2 antagonist and agonist in the treatment of cancers.

Incretin effect helps in regulating glucose homeostasis and maintaining glycaemic control within the human body. This effect is achieved by the two naturally occurring incretin hormones: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Such hormones released by specialized entero-endocrine cells of the gastrointestinal tract cause insulin augmentation after food consumption. However, incretin effects are impaired in type 2 diabetic, primarily attributed to the deterioration of GLP-1 function along with decreased GLP-1 receptor expression. Targeting this hormone has, therefore, become an important therapeutic approach to treat this diabetic condition. Native GLP-1’s brief half-life and rapid proteolytic degradation have generated significant enthusiasm in uncovering the long-acting GLP-1 receptor (GLP-1R) agonists to manage type 2 diabetes. These synthetic peptides mimic the natural GLP-1 to activate GLP-1R and effectively exert various physiological benefits in terms of weight management, blood pressure, lipid profile, obesity and major adverse cardiovascular event. This review paper provides insights into the structure, function and expression of GLP-1 and its receptor. It also summarizes existing literature regarding different types of GLP-1 receptor agonists, their effects on blood pressure and how they exert their actions. While animal models have contributed significantly to this area of study, the scarcity of human studies is noted, indicating a need for more investigation in this domain. Expanding research in humans will help in comprehending the impact of GLP-1 receptor agonists on blood pressure regulation and their underlying mechanisms.

Zika Virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique charac-teristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the ab-sence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce in vitro infection of A549 epithelial cells, a well-known cell model for flaviviruses infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to down-regulate adiponectin receptor expression and thereby limit adi-ponectin signaling.

Background: The clinical impact of vasopressin in hemorrhagic shock remains largely unknown. Objective: This systematic review and meta-analysis was designed to investigate the effects of vasopressin receptor agonists during the resuscitation of hemorrhagic shock. Methods: A systematic search of PubMed (MEDLINE), Scopus, and PubMed Central was conducted for relevant articles. Preclinical (animal) and clinical studies were included. The primary objective was to investigate the correlation of vasopressin receptor agonist use with mortality and various hemodynamic parameters. Results: Data extraction was possible in 13 animal studies and two clinical studies. Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents [RR (95%CI): 1.17 (0.67, 2.08); p=0.562; I2 = 50%]. The available data were insufficient to conduct a meta-analysis assessing the effect of vasopressin receptor agonists on hemodynamics. Drawing safe conclusions from animal studies was challenging, due to significant heterogeneity in terms of species and dosage of vasopressin receptor agonists across studies. Conclusions: Differences in risk of mortality between patients who received a vasopressin receptor agonist were not statistically significant when compared to those who were not treated with such agents after hemorrhagic shock.

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, Glucagon-Like Peptide-1 Receptor Ag-onists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aimed to investigate how the GLP-1RA Exendin-4 (Ex-4) affects the mi-croRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from untreated, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment path-way analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, in-sulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigations.

Purpose: While resultant maximal voluntary contraction (MVC) is commonly used to assess muscular performance, the simultaneous activation of antagonist muscles could dramatically underestimate the strength of the agonist muscles. While quantification of antagonist torque has been performed in plantar- (PF) and dorsi-flexion (DF) joint in isometric conditions, it has yet to be determined in anisometric (concentric and eccentric) conditions. Methods: The experiment was performed in 9 participants through 2 sessions (reliability). The MVCs in DF and PF were measured in isometric, concentric and eccentric conditions (10°.s^-1). Electromyographic (EMG) activities from the soleus, gastrocnemius medialis and lateralis, and tibialis anterior muscles were simultaneously recorded. The EMG biofeedback method was used to quantify antagonist torque, where participants were asked to maintain a level of EMG activity, corresponding to antagonist EMG activity and related to the muscle contraction type, according to a visual EMG bio-feedback displayed on a screen. Results: Resultant torque significantly underestimated agonist torque in DF MVC (30-65%) and to a lesser extent in PF MVC (3%). Triceps surae antagonist torque was significantly modified with muscle contraction type, showing higher antagonist torque in isometric (29 Nm) than eccentric (23 Nm, p < 0.001) and concentric (14 Nm, p < 0.001) conditions and resulting in modification of the DF MVC torque-velocity shape. The difference between DF eccentric and concentric MVC was attenuated when considered agonist torque (12%) rather than resultant torque (45%). Conclusion: Estimation of the antagonist torque in isometric or anisometric condition brings new insights to assessment of muscular performance and could result in costly misinterpretation in strength training and/or rehabilitation programs.

Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the cu-rative treatment of PCa. This paradigm shift contributed to the combined use of androgen depri-vation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data high-light the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormo-nal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its effi-cacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. How-ever, cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with oval-bumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lym-phoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

The study evaluated the impact of supplementing ZH in combination with D3 on growth performance, energy efficiency, carcass traits, and meat quality of feedlot lambs. Thirty-two Dorper x Katahdin cross lambs (37.3±5.72 kg) were utilized in a 29 d experiment in a complete randomized block design with a 2x2 factorial structure consisting of two levels of ZH for 26 d (0 and 0.20 mg /kg PV-1) and two levels of D3 for 7 d (0 and 1.5x106 IU/d-1). ZH improved (P≤0.05) average daily gain (ADG) and feed efficiency by 9.9% and 17.8%, respectively, as well as hot carcass weight (HCW) and dressing carcass by 4.3% and 2.6%, respectively. (p≤0.03). However, ZH increased (p<0.01) muscle pH and Warner-Bratzler shear force (WBSF) (2.5 and 23.0%, respectively). D3 supplementation negatively affected (P≤0.02) dry matter intake (DMI) (last 7 d) and ADG by 15.7% and 18.1%. On the other hand, D3 improved the pH of the longissimus muscle (LM) by 1.7% (p=0.03) without affecting WBSF. When D3 was supplemented in combination with ZH, it was observed that meat quality was improved by reducing muscle pH compared to lambs treated only with ZH. However, D3 did not improve meat tenderness produced by ZH supplementation.

Stimulation of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) has shown beneficial effects in several acute inflammatory disease models. This study aims to examine whether treatment with the selective α7nAChR agonist PHA 568487 can dampen inflammation and thereby improve cardiac function after myocardial infarction in mice. The possible anti-inflammatory properties of α7nAChR agonist PHA 568487 were tested in vivo using the air pouch model and in a permanent occlusion model of acute myocardial infarction in mice. Hematology parameters and cytokine levels were determined. Infarct size and cardiac function were assessed via echocardiography 24 h and one week after the infarction. Treatment with α7nAChR agonist PHA 568487 decreased 12 (CCL27, CXCL5, IL6, CXCL10, CXCL11, CXCL1, CCL2, MIP1a, MIP2, CXCL16, CXCL12 and CCL25) out of 33 cytokines in the air pouch model of acute inflammation. However, α7nAChR agonist PHA 568487 did not alter infarct size, ejection fraction, cardiac output or stroke volume at 24 h nor at 7 days after the myocardial infarction compared with control mice. In conclusion, despite promising immunomodulatory effects in the acute inflammatory air pouch model, α7nAChR agonist PHA 568487 did not affect infarct size or cardiac function after a permanent occlusion model of acute myocardial infarction in mice. Consequently, this study does not strengthen the hypothesis that stimulation of the α7nAChR is a future treatment strategy for acute myocardial infarction when reperfusion is lacking. However, whether other agonists of the α7nAChR can have different effects remains to be investigated.

Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promote the reactive oxygen species (ROS) production leading to airway inflammation, hyper-responsiveness and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long acting β2 agonists (LABAs; salmeterol and formoterol) and a new extra-LABA (indacaterol). The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time-points after hydrogen peroxide (H₂O₂) stimulation. H₂O₂ production was measured with DCFH-DA by flow cytometry. Montelukast, fluticasone and salmeterol suppressed H₂O₂-induced ROS production. Indacaterol enhanced H₂O₂-induced ROS production. Budesonide and formoterol alone had no anti-ROS effects, but the combination of these two drugs significantly suppressed H₂O₂-induced ROS production. Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not be the only choice for asthma control. Montelukast may be also a good supplemental treatment for the poorly-controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

Mouse models of alcohol use disorder (AUD) revealed a subtype of purinergic receptors (P2X4Rs) as a promising target for AUD drug development. We have previously demonstrated that residues at the transmembrane (TM)-ectodomain interface and within TM1 segment contribute to the formation of an ethanol action pocket in P2X4Rs. In the present study, we tested the hypothesis that there are more residues in TM segments, which are important for ethanol sensitivity of P2X4Rs. Using site-directed mutagenesis and two-electrode voltage-clamp electrophysiology in Xenopus oocytes, we found that arginine at position 33 (R33) in the TM1 segment plays a role in ethanol sensitivity of P2X4Rs. Molecular models in both closed and open states provided evidence for interactions between R33 and aspartic acid at position 354 (D354) of the neighboring TM2 segment. Further work with mixtures of wild-type (WT) and reciprocal single (R33D:WT, D354R:WT) and double (R33D-D354R:WT) mutants confirmed the importance of this interaction for ethanol sensitivity, ivermectin action and channel function. Additionally, our findings suggest that valine at TM1 position 49 plays a role in P2X4R function by providing flexibility during channel opening. Collectively, these findings identified new activity sites, and suggest the importance of TM1-TM2 interaction for channel function and ethanol sensitivity of P2X4Rs.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

Background: The standard surgical approach to amputation has failed to evolve significantly over the past century. Consequently, standard amputations often fall short with regards to improving the quality-of-life (QoL) for patients. A modified amputation has been designed at both the transtibial (TTA) and transfemoral (TFA) level that incorporates agonist-antagonist myoneural interface (AMI) constructs to provide patients with a novel alternative to standard amputation. Here, we present the patient reported outcome measures (PROMs) amongst our lower extremity AMI amputees and demonstrate an overall significant improvement in their physical and mental wellbeing. Methods: Four PROMs surveys, 1) EQ-5D-3L, 2) Lower Extremity Functional Scale (LEFS), 3) PROMIS-57, 4) Short Form-36 (SF-36), and 5) Sickness Impact Profile (SIP), were administered to lower extremity AMI amputees pre-operatively (baseline) and at 6 weeks, 3 months, 6 months, 9 months, 12 months, 24 months, 36 months, and 48 months post-operatively between June 24th, 2018, and December 15th, 2022. The surveys were either administered during a clinic visit or emailed at the encounter timepoint. Study data was collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Brigham and Women’s Hospital. Analyses of collated data were performed by fitting a linear mixed model using SAS version 9.4 (SAS Institute, Cary, NC). Results: The cohort’s baseline and 12-month post-operative responses were compared to determine score improvement. The cohort demonstrated a significantly improved EQ-5D-3L index value (p<0.0001) and EQ VAS (p<0.0001) at 12-months post-operatively (n=22) when compared to baseline (n=28). The LEFS score significantly improved at 12-months post-operatively compared to baseline (p<0.0001) with a mean of 59.04 ± 3.14 (SE) at 12-months and a mean of 31.96 ± 2.84 (SE) at baseline. AMI patients demonstrated significantly improved scores across PROMIS-57 domains at 12-months compared to baseline scores; the p-value was <0.0001 for all domains except for the Depression domain where p=0.0181. The health domain scores significantly improved from baseline to 12-months post-operation for all SF-36 domains. Lastly, the SIP indicated a significant decrease in overall dysfunction from baseline to 12-months post-operation (p<0.0001). Conclusions: Modified lower extremity amputation with AMI construction has the potential to provide amputees with increased quality-of-life when compared to the pre-operative state. However, further investigation is necessary to determine whether the patient reported outcome measures of the AMI amputee cohort are superior to those who receive a standard amputation.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

There are no investigations about the outcomes of idiopathic PVCs catheter ablation (CA) in athletes compared to sedentary population. We conducted a prospective single-centre observational study. The primary and secondary procedural outcomes were premature ventricular contractions (PVCs) post-ablation reduction in athletes vs. non-athletes group and in agonist vs. leisure-time athletes. The third was the evaluation of the resumption of physical activity and the improvement of symptoms in agonist and leisure-time athletes. From January 2020 to October 2022 we enrolled 79 patients with RVOT/LVOT/fascicular PVC presumed origin. The median percentage of decrease between the pre-procedure and post-procedure Holter monitoring in non-athletes group was 96 (IQR 68 – 98) and 98 in athletes group (IQR 92 – 99) (p=0,08). Considering the athletes, the median percentage of decrease in PVCs number was 98 (IQR 93-99) and 98 (IQR 87-99) respectively in leisure-time and agonistic athletes (p=0,42). Sixteen (70%) leisure time and 17 (90%) agonist athletes (p=0,24) have resumed physical activity 3 months after PVCs CA; among agonistic athletes, 59% have resumed competitive physical activity. Much of leisure-time (88%) and agonist (70%) athletes experienced an improvement in symptoms after ablation. PVC CA was effective and safe in both groups, reducing symptoms and allowing a quick and safe return to sports activities in athletes.

Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic machinery in macrophages, led by the α7-nAChR, facilitates the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.