Extracellular vesicles derived from monomeric α-synuclein-treated microglia ameliorate neuroinflammation by delivery of miRNAs targeting PRAK.

Parkinson's disease (PD) is characterized by the formation of Lewy body, which mainly contains misfolded α-synuclein. Microglial activation plays a role in neurodegeneration. The pathologically oligomeric α-synuclein promotes inflammatory microglia, while physiologically monomeric α-synuclein induces anti-inflammatory microglia, the relationship between these two forms in activating microglia and the molecular mechanism is essentially unknown. In this study, using in vivo and in vitro models, we challenged primary or BV2 microglia with exogenous stimuli including α-synuclein. We examined microglial activation and the underlying mechanism by Western blot, RT-PCR, ELISA, IF, FCM, miRNA sequencing and bioinformatic analysis. Oligomeric α-synuclein activatedmicroglia via theinvolvement of the PRAK/MK5 pathway. The specific PRAK inhibitor GLPG0259 could mitigate microglial activation insulted by oligomeric α-synuclein. Monomeric α-synuclein regulated theanti-inflammatory microglia by delivering microglia-derived extracellular vesicles (EVs) in vitro and in vivo. Furthersequencingand bioinformatic analysis of microglial EVs-associated miRNAs indicatedthatmost of these miRNAs targeted PRAK. These results suggest that PRAK serves as an intersection in microglial activation when challenged with conformationally different α-synuclein. EVs derived from microglia treated with monomeric α-synuclein promote anti-inflammatory microglia by delivering miRNAs that target PRAK into recipient microglia.

Integrated analysis of metabolomic and transcriptomic profiling reveals the effect of Buyang Huanwu decoction on Parkinson's disease in mice.

BACKGROUND: Parkinson's disease (PD) is a common, complex, and chronic neurodegenerative disorder involved in multi-system. At present, medicine for PD has many limitations. Buyang Huanwu decoction (BHD), a famous traditional Chinese medicinal (TCM) formulae, is used in the treatment of PD clinically in China. However, the therapeutic mechanism is still unknown. PURPOSE: We aimed to explore the pharmacological mechanism of BHD alleviating PD through an integrated liver metabolome and brain transcriptome analysis. METHODS: The mice with PD were induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral tests and immunohistochemistry were used to evaluate the neuroprotective effects of BHD. The non-targeted metabolomics analysis was conducted to profile differentially accumulated metabolites (DAMs) in the liver using a UHPLC-Q-Exactive MS/MS method. The differentially expressed genes (DEGs) in the brain were investigated by transcriptomic analysis on an Illumina sequencing platform. The correlations of DAMs and DEGs were investigated using an integrated metabolomic and transcriptomic approach. RESULTS: The results of behavioral tests and immunohistochemistry proved the alleviated effects of BHD on PD symptoms. A total of 14 and 36 DAMs were detected in the groups treated with low- (L group) and high-dose (H group) BHD respectively under the positive ion mode. Compared with the PD model group (M group), three enriched pathways including metabolic pathways, ABC transporters, and biosynthesis of amino acids were common in the L and H group. Transcriptomic analysis proved that BHD could regulate the expression of numerous genes, some of which were targeted by Ben-Ldopa such as Creb5, Gm45623, Ccer2, Cd180, Fosl2, Crip3, and Noxred1. Based on the integrated metabolomic and transcriptomic analysis, 7 metabolite-gene pairs were found in four comparisons, including C vs M, M vs P, M vs L, and M vs H, and 6 enriched pathways containing purine metabolism, glycine/serine/threonine metabolism, phenylalanine metabolism, carbon fixation in photosynthetic organisms, thiamine metabolism, and ABC transporters were overlapped. CONCLUSIONS: Though the underlying pharmacological mechanism of BHD is still lacking, we provided evidence that BHD could improve dopaminergic neurons in MPTP-induced PD mice by regulating liver metabolism and brain transcriptome. The correlation between the liver and the brain was preliminarily revealed in this study.

Solitary fibrous tumor of the mesentery: a case report and review of the literature.

Solitary fibrous tumors are rare mesenchymal tumors that typically arise from the pleura and rarely originate from the mesentery. We herein report a case involving a 66-year-old patient who presented with a mass on the left abdomen. This mass had been incidentally noticed 10 years earlier. The patient sometimes experienced abdominal pain. Physical examination revealed an irregular mass, which was resected. A biopsy of the mass revealed that it was a solitary fibrous tumor originating from the mesentery of the small intestine. The patient was discharged 1 week after surgery and had an uneventful clinical course throughout the 4-month postoperative follow-up.

Platelet distribution width as a marker for predicting lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is an important manifestation of systemic lupus erythematosus (SLE). The aim of this study was to investigate the predictive value of platelet distribution width (PDW) in LN. METHODS: A retrospective study involving 212 SLE patients and 201 healthy controls were performed. All clinical characteristics and laboratory data were collected from their medical records. RESULTS: The level of PDW was significantly decreased in SLE patients, which was negatively correlated with SLE disease activity index 2000 (SLEDAI-2K) score, disease duration, and 24-hour (24-h) urine protein, while positively correlated with serum IgG and IgM. There were more LN patients in low-PDW group than normal-PDW and high-PDW groups. In low-PDW group, SLEDAI-2K score, 24-h urine protein level, and anti-dsDNA antibody level was significantly higher, while serum IgG level was markedly lower. Moreover, PDW was negatively correlated with 24-h urine protein and disease duration, and it was positively correlated with serum IgG in LN patients. In addition, the area under the ROC curve of PDW was 0.87 and the optimal clinical cutoff level was 12.9, which provided a 87.41% sensitivity and a 74.63% specificity. Decreased PDW combined with high 24-h urine protein exhibited an excellent diagnostic value for LN. Importantly, 16.67% LN patients with negative 24-h urine protein can be detected in low PDW group. CONCLUSION: PDW may be a potential marker for predicting LN. Low PDW accompanied with high 24-h urine protein may be a useful indicator for diagnosing LN.

Using a mixture of wastewater and seawater as the growth medium for wastewater treatment and lipid production by the marine diatom Phaeodactylum tricornutum.

This study was conducted to evaluate the potential of the marine diatom Phaeodactylum tricornutum in nutrient removal coupled with biodiesel production using different ratios of mixed municipal wastewater (MW) and seawater (SW) as the growth medium. The results indicated that P. tricornutum exhibited high nutrient removal efficiency with the ratios of MW: SW = 1:1 and MW: SW = 2:1, e.g. 87.7-89.9% for chemical oxygen demand (COD), 82.2-86.7% for total nitrogen (TN), 96.0-97.0% for total phosphorus, and 76.9-84.2% for ammonium (NH3-N). Significantly higher biomass and lipid productivity were obtained with aeration. The highest lipid productivity of P. tricornutum was 54.76 mg/L/day, which was obtained with a two-step cultivation using the ratio of MW: SW = 1:1 by diluting half of the mixture and bubbling with 5% CO2 during the second step. These results suggested that the marine diatom P. tricornutum exhibited great potential for using mixed wastewater for wastewater treatment and biodiesel production.

SO2 derivatives and As co-exposure promote liver cancer metastasis through integrin αvß3 activation.

Arsenic (As) and sulfur dioxide (SO2) are two environmental pollutants that have been shown to promote the development of human cancer. In recent years, due to increased pollution, humans are often exposed to SO2, in addition to As. Despite the development and implementation of standards for environment and air quality, cases of disease caused by As or SO2 continue to rise alarmingly. It is currently unknown whether simultaneous exposure to As and SO2 results in increased cancer promoting activity. In this study, concentrations of As and SO2 below the limits established by the world health organization (WHO) in force environmental standards (concentrations of As should be lower than 1×10-2 mg/L and SO2 should be lower than 50 µg/m3), were employed to investigate possible, long-term, synergistic effects of As and SO2, by using cell-based assays. We found that co-exposure to these pollutants significantly promotes HepG2 cancer cell migration, while As or SO2 alone have no remarkable effects. Integrins αvß3 play a key role in this process, as cilengitide, an integrin αvß3 inhibitor, substantially prevented As and SO2-induced cell migration. MMPs, IL-8, and TGF-ß were also involved in the induced cell migration. In summary, combined exposure to As and SO2 promotes integrin-dependent cell migration and may be of relevance for the activation of mechanisms underlying liver cancer progression.

Arsenic and sulfur dioxide co-exposure induce renal injury via activation of the NF-κB and caspase signaling pathway.

Although emerging evidence suggests positive association of arsenic (As) or sulfur dioxide (SO2) exposure with human diseases, reports concerning the effects of co-exposure of As and SO2 are lacking. Moreover, there is insufficient information in the literature about As and SO2 co-exposure to renal injury. In this study, we focus on the environmental problems of excessive As and SO2 that co-exist in many coal consumption areas. We used both C57BL/6 mice and 293T cells to detect toxicities of As and SO2 exposure alone or in combination. Our results showed that co-exposure significantly increased the hazard compared with exposure to As or SO2 alone. Mouse kidney tissue slices showed that co-exposure caused more severe diffuse sclerosing glomerulonephritis than As and SO2 exposure alone. Meanwhile experiments showed that apoptosis was aggravated by co-exposure of As and SO2 in 293T cells. Because As and SO2 cause cell toxicity through increasing oxidative stress, next we detected ROS and other oxidative stress parameters, and the results showed oxidative stress was increased by co-exposure compared with the other three groups. The expression levels of downstream genes in the NF-κB and caspase pathways were higher in the co-exposure group than in the groups of As or SO2 exposure alone in mice and 293T cells. Based on the above results, co-exposure could induce higher toxicity in vitro and in vivo compared with single exposure to As or SO2, indicating that people living in places that contaminated by As and SO2 may have higher chance to get renal injury.

Toxicological effects of bisphenol A exposure-induced cancer cells migration via activating directly integrin ß1.

Bisphenol A (BPA) is an important chemical that widely used in our life. Mounting evidences show that BPA can leak into environment, which associates with the health risks, such as initiation and metastasis of cancer, but the mechanisms still need to be interpreted. Integrin ß1 is the most known subunit in integrin family, its abnormal expression and activation are tightly linked to tumorigenesis and a number of hallmarks of cancer. Here we show that environmental concentration (10-8 M) of BPA exposure can quickly activate integrin ß1 to induce cancer cell migration, and this effect is proved as a direct interaction between BPA and integrin ß1, which is independent from classical or non-canonical estrogen receptors. The data further indicates that residues S134, D137 and E229 in integrin ß1 played important roles in the interaction as predicted by AutoDock Vina, and confirmed by spectroscopy and native-PAGE. The study is the first to show a tumorigenic mechanism of BPA on tumor metastasis by the direct activation of integrin ß1 molecule, and give rise to profound concerns about widespread use of BPA in the manufacture of plastics and human health.

The expression of molecule CD28 and CD38 on CD4⁺/CD8⁺ T lymphocytes in thymus and spleen elicited by Schistosoma japonicum infection in mice model.

Schistosomiasis caused by human schistosomes such as Schistosoma japonicum (S. japonicum) is considered as an immune-related disease. It was demonstrated that specific cytokine antibodies' response elicited by S. japonicum infection was gradually downregulated with the progress of the disease, resulting in a Th1/Th2 polarization and suppression of immune response. CD28 (cluster of differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival, and CD38 is an activating marker of T lymphocyte with high expression in many acute or chronic infections. The immune signature of CD28null T cells in the peripheral circulation associates with chronic inflammation in many diseases, such as HIV and CMV infection. In the thymus, CD28 expression on developing thymocytes appears to play a role for their selection, and it synergizes with CD38 to induce apoptosis of DP (double-positive) thymocytes. Few reports about CD28 and CD38 have been published in schistosomiasis. Here, we investigated the dynamic patterns of the expression of molecules CD28 and CD38 on CD4(+)/CD8(+) T lymphocytes of the thymus and spleen in mice model with S. japonicum infection. Our data indicated that at an early period of infection, the frequency of CD8(+)CD28(-) T cell in the spleen decreased significantly, but higher at chronic infection than that in control. However, it demonstrated an increasing trend in the thymus with the progression of infection. The frequency of CD4(+)CD28(-) T cells increased from acute infection in the thymus, while from chronic infection in the spleen. The expression of CD38 on CD8(+) T cells began to increase at 4 weeks post infection both in the thymus and spleen; its elevated expression on CD4(+) T cells emerged at 6 weeks post infection in the thymus and at 10 weeks post infection in the spleen. Praziquantel (PZQ) treatment could partially restore the frequency of CD28(+) T cell of CD4(+) T cells and CD38(+) T cell of CD8(+)/CD4(+) T cells in the spleen and CD38(+) T cell in the thymus. We hypothesized that the reactivation of S. japonicum infection may trigger expansion of CD28(-) T cells and hence mediate systemic inflammation. We speculated that CD8(+)CD28(-) T cell might be involved in immune modulation and CD8(+)CD28(-) T cell may be a crucial part in pathogenesis, which can provide further knowledge of the sophisticated mechanism of immuno-downregulation in schistosomiasis and potential treatment target.

GRP78 is implicated in the modulation of tumor aerobic glycolysis by promoting autophagic degradation of IKKß.

Compared with normal differentiated cells, cancer cells take up much more glucose and metabolize it mainly via aerobic glycolysis. This metabolic phenotype is characterized with high expression of glucose transporters (Gluts) and pyruvate kinase M2 (PKM2). Glucose regulated protein 78 (GRP78) is a glucose-sensing protein and frequently up-regulated in cancer cells, however, whether it is directly implicated in glucose metabolism remains to be elucidated. Here we report that upon glucose deficiency, the induction of GRP78 resulted in enhanced HIF-1α transcription, accompanied by a transient increased expression of Glut-1. In addition, GRP78 was likely to facilitate the membrane translocation of Glut-1 via protein-protein interaction. Glucose starvation-stimulated GRP78 also impaired the expression of PKM2 but promoted the expression of mitochondrial pyruvate dehydrogenase A (PDHA) and B (PDHB), resulting in the metabolic shift from glycolysis to the TCA cycle. Interestingly, the inhibition of PKM2 by GRP78 was abrogated when glucose supply was restored, suggesting that GRP78 and PKM2 expressions are adaptable to the nutritional levels in the microenvironment. Further mechanistic study indicated that GRP78 overexpression activated the Class III PI3K-mediated autophagy pathway and induced autophagic degradation of IKKß, which caused inactivation of NF-κB pathway and subsequently altered the expression of PKM2 and HIF-1α. Our study establishes GRP78 and PKM2 as the crucial molecular links between cancer cell glucose metabolism and tumor microenvironment alterations.

Genome mining offers a new starting point for parasitology research.

Parasites including helminthes, protozoa, and medical arthropod vectors are a major cause of global infectious diseases, affecting one-sixth of the world's population, which are responsible for enormous levels of morbidity and mortality important and remain impediments to economic development especially in tropical countries. Prevalent drug resistance, lack of highly effective and practical vaccines, as well as specific and sensitive diagnostic markers are proving to be challenging problems in parasitic disease control in most parts of the world. The impressive progress recently made in genome-wide analysis of parasites of medical importance, including trematodes of Clonorchis sinensis, Opisthorchis viverrini, Schistosoma haematobium, S. japonicum, and S. mansoni; nematodes of Brugia malayi, Loa loa, Necator americanus, Trichinella spiralis, and Trichuris suis; cestodes of Echinococcus granulosus, E. multilocularis, and Taenia solium; protozoa of Babesia bovis, B. microti, Cryptosporidium hominis, Eimeria falciformis, E. histolytica, Giardia intestinalis, Leishmania braziliensis, L. donovani, L. major, Plasmodium falciparum, P. vivax, Trichomonas vaginalis, Trypanosoma brucei and T. cruzi; and medical arthropod vectors of Aedes aegypti, Anopheles darlingi, A. sinensis, and Culex quinquefasciatus, have been systematically covered in this review for a comprehensive understanding of the genetic information contained in nuclear, mitochondrial, kinetoplast, plastid, or endosymbiotic bacterial genomes of parasites, further valuable insight into parasite-host interactions and development of promising novel drug and vaccine candidates and preferable diagnostic tools, thereby underpinning the prevention and control of parasitic diseases.

AcCystatin, an immunoregulatory molecule from Angiostrongylus cantonensis, ameliorates the asthmatic response in an aluminium hydroxide/ovalbumin-induced rat model of asthma.

Epidemiological surveys have demonstrated that helminth infections are negatively related to atopic diseases, including asthma. Defining and characterising specific helminth molecules that have excellent immunomodulatory capacities as potential therapeutics for the treatment or prophylaxis of allergic manifestations are of great interest. AcCystatin, a cystatin protease inhibitor of Angiostrongylus cantonensis, is a homologue of other nematode cystatins with immunoregulatory properties. Here, we aim to determine the effects of AcCystatin on an ovalbumin/aluminium hydroxide (OVA/Al[OH]3)-induced rat model of asthma. Wistar rats were randomly divided into four groups, including a control group, an OVA/Al[OH]3-induced asthma group, a group receiving AcCystatin immunisation prior to OVA/Al[OH]3-induced asthma and a group receiving AcCystatin treatment after OVA/Al[OH]3-induced asthma. The numbers of eosinophils, basophils, neutrophils, lymphocytes and monocytes in the peripheral blood and of eosinophils in the bronchoalveolar lavage fluid (BALF) were counted for each animal. The expression levels of the cytokines interferon-γ, interleukin (IL) 4, IL-5, IL-6, IL-10, IL17A and tumour necrosis factor receptor-α in BALF, of OVA-specific immunoglobulin E in BALF and serum and of the chemokines eotaxin-1, eotaxin-2, eotaxin-3, MCP-1 and MCP-3 in lung tissue were measured. In addition, the degree of peribronchial and perivascular inflammation and the intensity of goblet cell metaplasia were qualitatively evaluated. The sensitised/challenged rats developed an extensive cell inflammatory response of the airways. AcCystatin administration significantly reduced the cellular infiltrate in the perivascular and peribronchial lung tissues and reduced both goblet mucous production and eosinophil infiltration. The rats that were treated with AcCystatin before or after sensitisation with OVA showed significant decreases in eotaxin-1, eotaxin-3 and MCP-1 expression in the lung tissue. The production of IL-4, IL-5, IL-6 and IL-17A and of OVA-specific IgE antibodies was also significantly reduced in AcCystatin-treated rats compared with untreated asthmatic rats. The AcCystatin treatment was associated with a significant increase in IL-10 levels. Our present findings provide the first demonstration that AcCystatin is an effective agent in the prevention and treatment of the airway inflammation associated with asthma.

Abnormal liver function in different patients with Schistosoma japonicum.

Schistosomiasis japonica, caused by Schistosoma japonicum, is still a serious public health problem in China. It is important for schistosomiasis control to prevent from infection and advanced patients. Recent years, however, the form of the prevalence of schistosomiasis japonica in China was changed these days. Paying attention to the quality of life of these patients already infected with S. japonicum becomes a new objective to schistosomiasis control program. Although most of the chronic infections with S. japonicum will finally appear as liver fibrosis symptoms, it is still unknown liver function abnormalities in patients with severe forms of schistosomiasis, and there is also no evidence whether S. japonicum infection will directly cause damage to liver cells. Thus, this study investigated 494 patients diagnosed with S. japonicum (87.7%) and 69 healthy subjects from a endemic areas belonging to Jiangxi Province of China and aimed to evaluate the liver function abnormalities in patients with severe forms of schistosomiasis and possible associations with coinfection with HBV. The results showed that the hepatic metabolism situation significantly changed in patients infected with S. japonicum; meanwhile, the abnormal rates of ALT and AST in patients with schistosomiasis were significantly higher than that in the control group, which confirmed that patients infected with S. japonicum not only had damaged liver function but also the hepatic cells were directly influenced. And the coinfection of CHB and schistosomiasis japonica can be a risk factor for more serious outcomes in patients from endemic areas. These results give us the advice that in the further treatment of patients infected with S. japonicum, especially these coinfections, we should better give the routine liver-protection treatment in advance.

Linalool, derived from Cinnamomum camphora (L.) Presl leaf extracts, possesses molluscicidal activity against Oncomelania hupensis and inhibits infection of Schistosoma japonicum.

BACKGROUND: Schistosomiasis japonicum remains a considerable economic and public health concern in China, the Philippines and Indonesia. Currently available measures to control the unique intermediate host Oncomelania hupensis are frequently associated with severe side effects. Previous studies have demonstrated that linalool-rich extracts from various plants exhibited promising biological activities including cytotoxic, anti-microbial and anti-parasitic properties. METHODS: We identified the components of leaf extracts from Cinnamomum camphora by gas chromatography coupled to mass spectrometry (GC-MS) and investigated molluscicidal and larvicidal effects of linalool against O. hupensis and Schistosoma japonicium. The ultrastructural alterations in gills, salivary gland, stomach and hepatopancreas of snails were observed under the light microscope and transmission electron microscope, and lesions to tegument of cercaria were examined under a light microscope and fluorescence microscope. We then evaluated the effects of linalool on skin penetration and migration of schistosomula and adult survival by measurement of worm burden and egg counts in Balb/C mice infected with linalool-treated cercariae. RESULTS: In the present work, 44 components were identified from the leaf extracts of C. camphora, of which linalool was the most abundant constituent. Linalool exhibited the striking molluscicidal and larvicidal effects with LC50 = 0.25 mg/L for O. hupensis and LC50 = 0.07 mg/L for cercaria of S. japonicium. After exposure to linalool, damage to the gills and hepatopancreas of the snails, and to the tegument and body-tail joint of cercariae was apparent. In addition, linalool markedly reduced the recovered schistosomulum from mouse skin after challenge infection, and therefore decreased the worm burden in infected animals, but not fecundity of female adults of the parasite. CONCLUSIONS: Our findings indicated that linalool might be a novel chemotherapeutic agent against S. japonicium and the snail intermediate host.

Eosinophil chemotactic chemokine profilings of the brain from permissive and non-permissive hosts infected with Angiostrongylus cantonenis.

Angiostrongylus cantonensis invasion primarily cause heavy or negligible eosinophic meningitis and meningoencephalitis in the brain of non-permissive and permissive hosts, respectively. Chemokines are effective leukocyte chemoattractants and may play an essential role in mediating eosinophil recruitment in angiostrongyliasis. In the present study, we comparatively analyzed changes in peripheral and CSF eosinophil counts, and expression profilings of eosinophil chemotactic chemokines in A. cantonensis-infected mice (CCL 2, CCL 3, CCL 5, CCL7, CCL 8, CCL 11, CCL 12, CCL 24 and CCL 28) and rats (CCL 2, CCL 3, CCL 5, CCL 11 and CCL 12) were explored at 1, 2, 5, 7, 14, and 21 days post-infection (dpi), and found significantly elevated numbers of eosinophils in blood and CSF of infected mice after 5 dpi, while significant increases of eosinophils in blood and CSF of infected rats were detected after 5 and 14 dpi, respectively. The kinetics of CSF eosinophilia is basically correlated with eosinophil chemotactic chemokine levels in brains of infected animals at each time point. Interestingly, less CSF eosinophils and infiltration of eosinophils in the brain were noted in rats than in mice, though extremely high levels of chemokines were also maintained in the brains of infected rats at 21 dpi. We further described CCL 11 (eotaxin), a previously reported eosinophil chemotactic factor in angiostrongyliasis, was mainly released from activated microglia in mice and rats infected with A. cantonensis. Our results reveal that different complicated chemokine networks mediate recruitment of eosinophils between permissive and non-permissive hosts during A. cantonensis infection, and provide promising targets for clinical treatment of angiostrongyliasis.

Correlation of serum ß2-microglobulin levels with prostate-specific antigen, Gleason score, clinical stage, tumor metastasis and therapy efficacy in prostate cancer.

BACKGROUND AND AIMS: Despite previous reports implying a role of ß2-microglobulin (ß2M) in the development of prostate cancer (PCa), the correlation of serum ß2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of ß2M in patients with PCa and explore the potential use of ß2M as a tumor marker for diagnosis, treatment and prognosis of PCa. METHODS: Serum ß2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum ß2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed. RESULTS: Our results showed that: (i) PCa patients had significantly higher levels of ß2M compared to those of patients with BPH or those of healthy controls. (ii) Serum ß2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of ß2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum ß2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease. CONCLUSIONS: Our results demonstrate that serum ß2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum ß2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa.