Ferroptosis, an iron-dependent programmed cell death process driven by reactive oxygen species-mediated lipid peroxidation, is regulated by several metabolic processes, including iron metabolism, lipid metabolism, and redox system. Macrophages are a group of innate immune cells that are widely distributed throughout the body, and play pivotal roles in maintaining metabolic balance by its phagocytic and efferocytotic effects. There is a profound association between the biological functions of macrophage and ferroptosis. Therefore, this review aims to elucidate three key aspects of the unique relationship between macrophages and ferroptosis, including macrophage metabolism and their regulation of cellular ferroptosis; ferroptotic stress that modulates functions of macrophage and promotion of inflammation; and the effects of macrophage ferroptosis and its role in diseases. Finally, we also summarize the possible mechanisms of macrophages in regulating the ferroptosis process at the global and local levels, as well as the role of ferroptosis in the macrophage-mediated inflammatory process, to provide new therapeutic insights for a variety of diseases.
Ferroptosis/physiology* ; Macrophages/metabolism* ; Humans ; Animals ; Iron/metabolism* ; Reactive Oxygen Species/metabolism* ; Lipid Peroxidation/physiology* ; Inflammation/metabolism*

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Galectins(Gals)are evolutionarily conserved proteins that bind to β-galactoside containing glycans.Abnormal expression of Gals is associated with the development,progression,and metastasis of different types of cancer.Among the 11 Gals identified in humans,the roles of Gal-1 and Gal-3 have been extensively investigated in various tumors.Here,we summarize the roles of overly expressed Gal-1 and Gal-3 in the pathogenesis of hepatocellular carcinoma(HCC).The overexpression of Gal-1 and Gal-3 correlates with tumor growth,HCC cell migration and invasion,tumor aggressiveness,metastasis,and poor prognosis.A potentially promising future treatment strategy for HCC may include the combination of immunotherapy with Gal-1 inhibition.Additional research is warranted to investigate targeting Gal-1 and Gal-3 for HCC treatment.

The incidence of hepatocellular carcinoma(HCC)has been increasing for decades.This disease has now risen to become the sixth most common malignancy overall,while ranking as the third most frequent cause of cancer mortality.While several surgical interventions and loco-regional treatment options are available,up to 80％ of patients present with advanced disease not amenable to standard therapies.Indeed,traditional cytotoxic chemotherapeutic agents are notoriously ineffective and essentially play no role in the management of affected patients.This has led to an enormous need for more effective sys-temic therapeutic options.In recent years,immunotherapy has emerged as a potentially viable and exciting new alternative for the treatment of HCC.Although the current immunotherapeutic options remain imperfect,various strategies can be employed to further improve their efficacy.New findings have revealed epigenetic modulation can be effective as a new approach for improving HCC immuno-therapy.Studying the gut microbiome(gut-liver axis)can also be an interesting subject in this regard.Here,we explore the latest insights into the role of immunotherapy treating HCC,both mono and in combination with other agents.We also focus on the impact of epigenetic drugs and the microbiome in the overall effectiveness of HCC immunotherapy.

OBJECTIVETo explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats.

METHODSForty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy.

RESULTSCompared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group.

CONCLUSIONZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

OBJECTIVETo elucidate the mechanism of Chinese tuina in treating sciatic nerve crush injury, and to detect the levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), which is thought to play an important role in nerve regeneration.

METHODSThirty-two adult male Sprague-Dawley rats were subjected to sciatic nerve crush injury and 16 rats (sham-operated group) went through a sham operation. Control group was given no treatment while tuina group received tuina therapy since day 7 post-surgery. Tuina treatment was performed once a day and lasted for 20 days. The sciatic functional index was examined every 5 days during the treatment session. The rats' gastrocnemius muscles were evaluated for changes in mass and immunohistochemistry techniques were performed to detect the levels of tPA and PAI-1.

RESULTSTuina therapy improved the motor function of sciatic nerve injured rats (P<0.05), however, it did not increase muscle volume (P<0.05). Tuina downregulated the levels of tPA and PAI-1 (P<0.05).

CONCLUSIONSThe present study implies that tuina treatment could accelerate rehabilitation of peripheral nerve injury.

BACKGROUND:The purpose of this study was to use point-of-care ultrasound (POCUS) to investigate the relationship between tobacco smoke exposure and the characteristics of the common carotid artery (CCA). The effect of both primary and secondary smoking on CCA properties was evaluated. METHODS:We performed a prospective cross-sectional study across 20 primary care clinics in Bandung, West Java, Indonesia in July 2016. Point of care ultrasound was performed on a convenience sample of Indonesian patients presenting to clinic. The CCA wall stiffness and carotid intima-media thickness (CIMT) were measured during diastole and systole. These measurements were correlated with smoke exposure and cardiovascular disease. RESULTS: We enrolled 663 patients in the study, with 426 patients enrolled in the smoking category and 237 patients enrolled in the second-hand smoke category. There was an overall positive correlation with the measured lifestyle factors and the ultrasound-measured variables in the group of individuals who smoked. For all variables, age seemed to contribute the most out of all of the lifestyle factors for the positive changes in CIMT and CCA wall stiffness. CONCLUSION:Our data yielded correlations between CCA properties and cardiovascular risk, as well as between CIMT and arterial stiffness. We were also able to demonstrate an increase in thickness of the CIMT in patients who have been exposed by tobacco through the use of ultrasound. Further large scale studies comparing patients with multiple cardiac risk factors need to be performed to confirm the utility of ultrasound findings of cardiovascular disease and stroke.