Structure elucidation and antiviral activity of a cold water-extracted mannogalactofucan Ts1-1A from Trametes sanguinea against human cytomegalovirus in vitro.

In this study, we purified a partially acetylated heteropolysaccharide (Ts1-1A) from the fruit bodies of Trametes sanguinea Lloyd through cold water extraction and serial chromatographic separation. The purified polysaccharide Ts1-1A (12.8 kDa) was characterized as a branched mannogalactofucan with a backbone of alternately connected 1,3-linked α-Fucp and 1,6-linked α-Galp, which was partially substituted by non-reducing end units of ß-Manp at O-2 and O-3 positions of 1,6-linked α-Galp. Ts1-1A showed pronounced anti-human cytomegalovirus activity at the concentration of 200 and 500 µg/mL in systematical assessments including morphological changes, western blotting, qPCR, indirect immunofluorescence and tissue culture infective dose assays. Moreover, Ts1-1A exerted its antiviral activity at two distinct stages of viral proliferation manifesting as significantly inhibiting viral protein (IE1/2 and p52) expression and reducing viral gene (UL123, UL44 and UL32) replication in the HCMV-infected WI-38 cells. At viral attachment stage, Ts1-1A interacted with HCMV and prevented HCMV from attaching to its host cells. While at early phase of viral replication stage, Ts1-1A suppressed HCMV replication by downregulating NQO1 and HO-1 proteins related to oxidative stress as an antioxidant. To sum up, Ts1-1A is a promising anti-HCMV agent which could be developed for HCMV infection prevention and therapy.

DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus.

The DNA damage response (DDR) is a signaling cascade that is triggered by DNA damage, involving the halting of cell cycle progression and repair. It is a key event leading to senescence, which is characterized by irreversible cell cycle arrest and the senescence-associated secretory phenotype (SASP) that includes the expression of inflammatory cytokines. Human cytomegalovirus (HCMV) is a ubiquitous pathogen that plays an important role in the senescence process. It has been established that DDR is necessary for HCMV to replicate effectively. This paper reviews the relationship between DDR, cellular senescence, and HCMV, providing new sights for virus-induced senescence (VIS).

Inhibition of mitochondrial calcium uptake by Ru360 enhances the effect of 1800 MHz radio-frequency electromagnetic fields on DNA damage.

Today, the existence of radio-frequency electromagnetic fields (RF-EMF) emitted from cell phones, wireless routers, base stations, and other sources are everywhere around our living environment, and the dose is increasing. RF-EMF have been reported to be cytotoxic and supposed to be a risk factor for various human diseases, thus, more attention is necessary. In recent years, interfere with mitochondrial calcium uptake by using mitochondrial calcium uniporter (MCU) inhibitor were suggested to be potential clinical treatment in mitochondrial calcium overload diseases, like neurodegeneration, ischemia/reperfusion injury, and cancer, but whether this approach increases the health risk of RF-EMF exposure are unknown. To address our concern, we did a preliminary study to determine whether inhibition of MCU will increase the genotoxicity of RF-EMF exposure in cells, and found that short-time (15 min) exposure to 1800 MHz RF-EMF induced significant DNA damage and cell apoptosis in mouse embryonic fibroblasts (MEFs) treated with Ruthenium 360 (Ru360), a specific inhibitor of MCU, but no significant effects on cell cycle, cell proliferation, or cell viability were observed. In conclusion, our results indicated that inhibiting MCU increases the genotoxicity of RF-EMF exposure, and more attention needs to be paid to the possible health impact of RF-EMF exposure under these treatments.

Comparison of anti-tumor activities and underlying mechanisms of glucuronomannan oligosaccharides and its sulfated derivatives on the hepatocarcinoma Huh7.5 cells.

Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro, and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates.

Suppressive effects of pterostilbene on human cytomegalovirus (HCMV) infection and HCMV-induced cellular senescence.

BACKGROUND: Human cytomegalovirus (HCMV), a member of the ß-herpesvirus family, causes the establishment of a latent infection that persists throughout the life of the host and can be reactivated when immunity is weakened. To date, there is no vaccine to prevent HCMV infection, and clinically approved drugs target the stage of viral replication and have obvious adverse reactions. Thus, development of novel therapeutics is urgently needed. METHODS: In the current study, we identified a naturally occurring pterostilbene that inhibits HCMV Towne strain replication in human diploid fibroblast WI-38 cells through Western blotting, qPCR, indirect immunofluorescence assay, tissue culture infective dose assays. The time-of-addition experiment was carried out to identify the stage at which pterostilbene acted. Finally, the changes of cellular senescence biomarkers and reactive oxygen species production brought by pterostilbene supplementation were used to partly elucidate the mechanism of anti-HCMV activity. RESULTS: Our findings revealed that pterostilbene prevented lytic cytopathic changes, inhibited the expression of viral proteins, suppressed the replication of HCMV DNA, and significantly reduced the viral titre in WI-38 cells. Furthermore, our data showed that pterostilbene predominantly acted after virus cell entry and membrane fusion. The half-maximal inhibitory concentration was determined to be 1.315 µM and the selectivity index of pterostilbene was calculated as 26.73. Moreover, cell senescence induced by HCMV infection was suppressed by pterostilbene supplementation, as shown by a decline in senescence-associated ß-galactosidase activity, decreased production of reactive oxygen species and reduced expression of p16, p21 and p53, which are considered biomarkers of cellular senescence. CONCLUSION: Together, our findings identify pterostilbene as a novel anti-HCMV agent that may prove useful in the treatment of HCMV replication.

Salidroside reduces neuropathology in Alzheimer's disease models by targeting NRF2/SIRT3 pathway.

BACKGROUND: Neurite dystrophy is a pathologic hallmark of Alzheimer's disease (AD). However, drug discovery targeting neurite protection in AD remains largely unexplored. METHODS: Aß-induced neurite and mitochondrial damage assays were used to evaluate Aß toxicity and the neuroprotective efficacy of a natural compound salidroside (SAL). The 5×FAD transgenic mouse model of AD was used to study the neuroprotective function of SAL. To verify the direct target of SAL, we used surface plasmon resonance and cellular thermal shift assays to analyze the drug-protein interaction. RESULTS: SAL ameliorates Aß-mediated neurite damage in cell culture. We further reveal that SAL represses mitochondrial damage in neurites by promoting mitophagy and maintaining mitochondrial homeostasis, dependent on an NAD-dependent deacetylase SIRT3. In AD mice, SAL protects neurite morphology, mitigates Aß pathology, and improves cognitive function, which are all SIRT3-dependent. Notably, SAL directly binds to transcription factor NRF2, inhibits its degradation by blocking its interaction with KEAP1 ubiquitin ligase, and then advances NRF2-mediated SIRT3 transcription. CONCLUSIONS: Overall, we demonstrate that SAL, a potential anti-aging drug candidate, attenuates AD pathology by targeting NRF2/SIRT3 pathway for mitochondrial and neurite protection. Drug discovery strategies focusing on SAL may thus provide promising therapeutics for AD.

Sulfated modification of hyaluronan tetrasaccharide enhances its antitumor activity on human lung adenocarcinoma A549 cells in vitro and in vivo.

Hyaluronan (HA) is a glycosaminoglycan polymer involved in cell phenotype change, inflammation modulation, and tumor metastasis progression. HA oligosaccharides have a higher solubility and drug-forming ability than polysaccharides. HA tetrasaccharide was reported as the smallest fragment required for inhibiting triple-negative breast cancer, but the anti-tumor activity of HA tetrasaccharide (HA4) and its sulfated derivatives in lung cancer is still unknown. In this study, HA4 was prepared via HA degradation by chondroitinase ABC (CSABC), while its sulfated derivatives were prepared by sulfur pyridine trioxide complex in N, N-dimethylformamide (DMF). Then, the anti-tumor activity was detected via MTT assay and xenograft tumor experiments, while the expression level change of apoptosis genes was analyzed by qRT-PCR. Electrospray mass spectrometry (ESI-MS) analysis showed several HA4 sulfated derivatives, GlcA2GlcNAc2 (SO3H)n contains 0-6 sulfation groups, which mainly contain 3-6, 2-3, and 0-1 sulfation groups were classified as HA4S1, HA4S2, and HA4S3, respectively. After the addition of 1.82 mg/mL HA4, HA4S1, HA4S2, and HA4S3, the cell viability of A549 cells was reduced to 81.2 %, 62.1 %, 50.3 %, and 65.9 %, respectively. Thus, HA4S2 was chosen for further measurement, the qRT-PCR results showed it significantly up-regulated the expression of genes in the apoptosis pathway. Moreover, HA4S2 exhibited stronger antitumor activity than HA4 in vivo and the tumor inhibition rate reached 36.90 %. In summary, this study indicated that the CSABC enzyme could effectively degrade HA into oligosaccharides, and sulfation modification was an effective method to enhance the antitumor activity of HA tetrasaccharides.

Structural characterization of a polysaccharide from Trametes sanguinea Lloyd with immune-enhancing activity via activation of TLR4.

A bioactive polysaccharide (TS2-2A) with a molecular weight of 15 kDa was isolated from Trametes sanguinea Lloyd, a medicinal food homologous fungus, by water extraction-alcohol precipitation and chromatographic separation. NMR analysis of polysaccharide and MS/MS analysis of its oligosaccharide indicated that TS2-2A featured a novel straight chain with a backbone of 1,3-α-d-glucopyranose and 1,4-ß-d-glucopyranose at a molar ratio of 1:4. Moreover, TS2-2A, recognized by Toll-like receptor 4 (TLR4), stimulated RAW 264.7 macrophages to release related cytokines and contributed to immune-enhancing effects. Briefly, with remarkable immune-enhancing activity and noncytotoxicity, TS2-2A was proposed to be a potential immune enhancer for supplementing drugs or functional foods.

Exposure to 10 Hz Pulsed Magnetic Fields Do Not Induce Cellular Senescence in Human Fetal Lung Fibroblasts.

Rapid population aging has led to a global burden of late-life diseases. As the largest risk factor for a multitude of age-related diseases, aging is not only the result of genotype but also closely related to external factors. With the rapid expansion in the usage of electromagnetic fields (EMFs), the effect of EMFs on aging has also attracted attention. Cells are the basic unit of organs and body tissues, and cellular senescence plays an important role in the aging process. The effect of EMFs on cellular senescence has been investigated in a few studies, but the information is limited, and the results are inconsistent; thus, further investigation is required. In this study, we investigated the effect of 10 Hz pulsed magnetic fields (MFs) on cellular senescence in a 2BS cell line, isolated from human fetal lung fibroblasts, and found that intermittent (1 d on/1 d off) exposure to 10 Hz pulsed MFs at 1.0 mT for 2 weeks induced DNA damage, but no other significant phenotype of cellular senescence in 2BS cells.

Sulphated glucuronomannan tetramer and hexamer from Sargassum thunbergii exhibit anti-human cytomegalovirus activity by blocking viral entry.

Human cytomegalovirus (HCMV) remains a major public health burden worldwide. The anti-HCMV activity of glucuronomannan oligosaccharides (Gs) and sulphated glucuronomannan oligosaccharides (SGs) was investigated. Among these Gs and SGs, G4S1 and G6S1 (higher sulphated glucuronomannan tetramer and hexamer) showed satisfactory anti-HCMV activity starting at 50 µg/mL and 10 µg/mL, respectively. The results of the morphology, western blotting, qPCR and TCID50 assay showed that they prevented lytic cytopathic changes, inhibited the expression of IE1/2 and UL44, and reduced the UL123 copy number and virus titre significantly. It was interesting to note that degree of sulphation and polymerization was more important for anti-HCMV activity. Moreover, the anti-HCMV activities of G4S1 and G6S1 were stable when stored at 4 °C, -20 °C, and -80 °C for at least three months and mainly occurred in the early stage of HCMV infection through the negative charge of the sulphate groups and the interaction between SGs and the host cells.

Structural analysis of a glucoglucuronan derived from laminarin and the mechanisms of its anti-lung cancer activity.

Laminarin (LA), a storage glucan, was purified from the brown alga Sargassum thunbergii. After specific oxidation using the stable nitroxyl radical, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), together with NaBr and NaClO, glucoglucuronan (LAO) was obtained. Compositional analysis of LAO showed a molar ratio of glucuronic acid (GlcA) to glucose (Glc) of 12.7: 1. Nuclear magnetic resonance (NMR) and mass spectroscopy (MS) showed LAO to have a backbone of (1 â†’ 3)-linked ß-D-GlcpA interspersed with (1 â†’ 3, 1 â†’ 6)-linked ß-D-Glcp, that was terminated with ß-D-GlcpA. LAO inhibited human lung cancer A549 cell proliferation in vitro. IC50 values at 12 h and 24 h were 2.70 mg/mL and 2.85 mg/mL, respectively. Western blotting showed that TSC2 was up-regulated at an LAO concentration of 3.80 mg/mL. FAK, PI3K, P-AKT and mTOR were down-regulated, indicating LAO inhibited cancer cell proliferation through the FAK/PI3K/AKT/mTOR pathway. Surface plasmon resonance (SPR) studies revealed that LAO showed an IC50 of 0.07 mg/mL inhibiting the binding of heparin to fibroblast growth factor 1 (FGF1) LAO inhibition of heparin binding to FGF2 fluctuated between 15% and 28%, suggesting that LAO inhibits A549 cell proliferation by selectively interacting with FGF1.

Inhibitory effects of piceatannol on human cytomegalovirus (hCMV) in vitro.

Human cytomegalovirus (hCMV) is a ubiquitous herpesvirus, which results in the establishment of a latent infection that persists throughout the life of the host and can be reactivated when the immunity is low. Currently, there is no vaccine for hCMV infection, and the licensed antiviral drugs mainly target the viral enzymes and have obvious adverse reactions. Thus, it is important to search for compounds with anti-hCMV properties. The present study aimed to investigate the suppressive effects of piceatannol on hCMV Towne strain infection and the putative underlying mechanisms using human diploid fibroblast WI-38 cells. Piceatannol supplementation prevented the lytic changes induced by hCMV infection in WI-38 cells. Furthermore, piceatannol suppressed the expression of hCMV immediate-early (IE) and early (E) proteins as well as the replication of hCMV DNA in a dose-dependent manner. Moreover, hCMV-induced cellular senescence was suppressed by piceatannol, as shown by a decline in the senescence-associated ß-galactosidase (SA-ß-Gal) activity and decreased production of intracellular reactive oxygen species (ROS). p16INK4a, a major senescence-associated molecule, was dramatically elevated by current hCMV infection that was attenuated by pre-incubation with piceatannol in a dose-dependent manner. These results demonstrated that piceatannol suppressed the hCMV infection via inhibition of the activation of p16INK4a and cellular senescence induced by hCMV. Together, these findings indicate piceatannol as a novel and potent anti-hCMV agent with the potential to be developed as an effective treatment for chronic hCMV infection.

Sulfated galactofucan from Sargassum thunbergii induces senescence in human lung cancer A549 cells.

Isolated compounds from Sargassum thunbergii (S. thunbergii) have shown to exhibit diverse biological activities, including anti-cancer activity. In this study, we examined the effect of sulfated galactofucan (SWZ-4-H), which was successfully isolated from S. thunbergii, and its underlying mechanism on human lung cancer (LC) A549 cell growth in vitro and in vivo. In vitro experiment indicated that SWZ-4-H decreased cell growth and number in a dose-dependent manner (P < 0.05 vs. control). Besides, cells treated with SWZ-4-H had irregular morphology, including increased cell volumes, and large nuclei, which suggested senescence-like changes. Moreover, SWZ-4-H increased senescence-related ß-galactosidase (SA-ß-Gal) staining in a dose-dependent manner; however, while lower (1 mg mL-1) concentration induced mainly senescence without causing cell death, higher dosage (3 mg mL-1) induced both senescence and cell death. The effect of SWZ-4-H was further confirmed by analyzing the expression of p53, p21, p16, and Rb (p-RB); SWZ-4-H significantly increased the expression of p53, p21, and p16 and decreased phosphorylated Rb (p-RB) in a dose-dependent manner. Moreover, in vivo experiment showed that SWZ-4-H significantly reduced the tumor volume without affecting the body weight. To sum up, our data indicated that SWZ-4-H could induce lung cancer senescence by regulating p53, p21, p16, and p-Rb, thus providing a novel perspective on anti-cancer mechanisms of SWZ-4-H in human lung cancer A549 cells.

Geoarchaeological evidence of the AD 1642 Yellow River flood that destroyed Kaifeng, a former capital of dynastic China.

Rising global temperatures will increase the number of extreme weather events, creating new challenges for cities around the world. Archaeological research on the destruction and subsequent reoccupation of ancient cities has the potential to reveal geological and social dynamics that have historically contributed to making urban settings resilient to these extreme weather events. Using a combination of archaeological and geological methods, we examine how extreme flood events at Kaifeng, a former capital of dynastic China, have shaped the city's urban resilience. Specifically, we focus on an extreme Yellow River flood event in AD 1642 that historical records suggest killed around 300,000 people living in Kaifeng. Our recent archaeological excavations have discovered compelling geological and archaeological evidence that corroborates these documents, revealing that the AD 1642 Yellow River flood destroyed Kaifeng's inner city, entombing the city and its inhabitants within meters of silt and clay. We argue that the AD 1642 flood was extraordinarily catastrophic because Kaifeng's city walls only partly collapsed, entrapping most of the flood waters within the city. Both the geology of the Yellow River floods as well as the socio-political context of Kaifeng shaped the city's resilience to extreme flood events.

Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway.

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.

Bone mineral density in patients with chronic heart failure: a meta-analysis.

OBJECTIVE: This study aimed to verify the existing relationship between bone mineral density (BMD) and chronic heart failure (CHF) by meta-analysis. METHODS: Databases, including PubMed, Web of Science, and Chinese National Knowledge Infrastructure, published in English or Chinese up to February 28, 2017, were searched for studies on the association between CHF and BMD. Two independent reviewers collected the relevant articles. The standard mean deviation (SMD) and 95% confidence interval were calculated for BMD with fixed- and random-effect models. Subgroup and sensitivity analyses were also conducted. RESULTS: A total of six studies (552 CHF and 243 non-CHF patients) were included. The results indicated that the patients with CHF had a lower total BMD compared with the non-CHF patients. Similar effects were also observed for femoral neck, arm, leg, and trunk BMD. However, no difference was observed in the lumbar spine BMD. The SMD of total BMD in New York Heart Association classes I or II (NYHA I or II) patients was -0.62, while that in NYHA III or IV patients was -0.87, and the SMD of femoral bone mineral density in NYHA I or II patients was -0.47, while that in NYHA III or IV patients was -1.07. Moreover, vitamin D and parathyroid hormone (PTH) were also found to be associated with CHF. CONCLUSION: Patients with CHF had a lower total BMD and femoral neck, arm, leg, or trochanter BMD than patients with non-CHF. Vitamin D reduced, whereas PTH increased, with the severity of CHF. The clinical significance of the present findings remains uncertain and should be confirmed by future studies.

Salidroside influences the cellular cross-talk of human fetal lung diploid fibroblasts: A proteomic approach.

Senescence is a complex multiple factor proces, which is still poorly understood. The purpose of this study was to find the proteome of cultured human fetal lung diploid fibroblasts (2BS) of different population doubling (PD), as well as the altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As a result, we found 16 proteins with two-fold variations in senescent cells or after SAL treatment, some being reduced such as reticulocalbin-1, heat shock protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha-1, and chloride intracellular channel 1. In contrast, 40S ribosomal protein SA, proteasome subunit alpha type-5, and zinc finger BED domain-containing protein 5 increased with cell age. Furthermore, heat shock protein beta-6, Zinc finger BED domain-containing protein 5 was increased in PD30 cells after 10 µM SAL treatment, whereas, elongation factor 1-delta, 6-phosphogluconolactonase, Nucleoside diphosphate kinase A, F-actin-capping protein subunit alpha-1, Probable ATP-dependent RNA helicase DDX41, Chloride intracellular channel 1, and Peroxiredoxin-6 were increased in PD50 cells after 10 µM SAL treatment. Some of these proteins were involved in the protein synthetic and degradative pathways, which emphasizes the metabolic disorder or functional impairment of cell senescence. Moreover, these proteins could be candidate biomarkers for evaluating the SAL anti-senescence effect.

C-Terminal Domain of Hemocyanin, a Major Antimicrobial Protein from Litopenaeus vannamei: Structural Homology with Immunoglobulins and Molecular Diversity.

Invertebrates rely heavily on immune-like molecules with highly diversified variability so as to counteract infections. However, the mechanisms and the relationship between this variability and functionalities are not well understood. Here, we showed that the C-terminal domain of hemocyanin (HMC) from shrimp Litopenaeus vannamei contained an evolutionary conserved domain with highly variable genetic sequence, which is structurally homologous to immunoglobulin (Ig). This domain is responsible for recognizing and binding to bacteria or red blood cells, initiating agglutination and hemolysis. Furthermore, when HMC is separated into three fractions using anti-human IgM, IgG, or IgA, the subpopulation, which reacted with anti-human IgM (HMC-M), showed the most significant antimicrobial activity. The high potency of HMC-M is a consequence of glycosylation, as it contains high abundance of α-d-mannose relative to α-d-glucose and N-acetyl-d-galactosamine. Thus, the removal of these glycans abolished the antimicrobial activity of HMC-M. Our results present a comprehensive investigation of the role of HMC in fighting against infections through genetic variability and epigenetic modification.