Nanoscale Magneto-mechanical-genetics of Deep Brain Neurons Reversing Motor Deficits in Parkinsonian Mice.

Here, we introduce the magneto-mechanical-genetic (MMG)-driven wireless deep brain stimulation (DBS) using magnetic nanostructures for therapeutic benefits in the mouse model of Parkinson's disease (PD). Electrical DBS of the subthalamic nucleus (STN) is an effective therapy for mitigating Parkinson's motor symptoms. However, its broader application is hampered by the requirement for implanted electrodes and the lack of anatomical and cellular specificity. Using the nanoscale magnetic force actuators (m-Torquer), which deliver torque force under rotating magnetic fields to activate pre-encoded Piezo1 ion channels on target neurons, our system enables wireless and STN-specific DBS without implants, addressing key unmet challenges in the DBS field. In both late- and early-stage PD mice, MMG-DBS significantly improved locomotor activity and motor balance by 2-fold compared to untreated PD mice. Moreover, MMG-DBS enabled sustained therapeutic effects. This approach provides a non-invasive and implant-free DBS with cellular targeting capability for the effective treatment of Parkinsonian symptoms.

Prognostic Effect of Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated Gastric Carcinomas Measured by Digital Image Analysis.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent tumor-infiltrating lymphocytes (TILs) and has a favorable prognosis. Tertiary lymphoid structures (TLS), characterized by ectopic aggregated lymphocytes with high-endothelial venules (HEV), are associated with favorable outcomes in various solid tumors. We hypothesized that EBVaGC, characterized by intense TILs, may be closely associated with TLS or HEV. To test this hypothesis, we digitally analyzed the TLS, HEV, and TILs in 73 surgically resected advanced EBVaGCs. For HEV, dual MECA-79 and CD31 dual immunohistochemistry were performed, and the ectopic expression of MECA-79 in tumor cells was measured. In 73 patients with EBVaGC, a high-TLS ratio was found in 29 (39.7%) cases, high-tumor-associated HEV density in 44 (60.3%) cases, and high-CD8+ TIL density in 38 (52.1%) cases. Ectopic tumor expression of MECA-79 was observed in 36 patients (49.3%) cases. A low-TLS ratio and tumor-associated HEV density were significantly associated with lymph node metastasis (P =.005 and.042, respectively). Ectopic MECA-79 expression was significantly associated with lymph node metastasis (P =.003). Patients with a low-TLS ratio (P =.038), low-HEV density (P =.042), and ectopic tumor MECA-79 expression (P =.032) had significantly worse prognoses. In conclusion, TLS ratio and HEV density affect the survival of patients with EBVaGC and may be related to the immune response that interrupts lymph node metastasis.

Suicidal ideation and attempt among young people living in gosiwons in South Korea.

INTRODUCTION: Young people living in gosiwons could be at high risk for suicide owing to inadequate living conditions and the social stigma towards them. However, this topic has not received adequate academic attention. Gosiwon is a type of small residence consisting of several tiny rooms densely packed together and usually does not meet minimum housing standards. However, gosiwons are favored by low-income groups, especially young people, because they are cheaper than other residences. This study aimed to examine the factors that increase the risk of suicidal ideation and attempt among young people living in gosiwons. METHODS: A sample of 300 young people aged 19-34 years living in gosiwons for over 6 months was analyzed. A set of multinomial logistic regression was conducted to examine the factors that differentiate the suicidal ideation and attempt group from the no-suicidal risk group. RESULTS: Approximately 30% of the study participants experienced suicidal ideation or attempted suicide. Among several risk factors, social exclusion and depressive symptoms distinguished the group with suicidal ideation from the no-risk group. Depressive symptoms were the only factor that differentiated the group with suicide attempts history from the no-risk group. CONCLUSION: The results emphasize the need to focus on social exclusion and depressive symptoms among young people living in poor housing conditions. Interventions to address social exclusion and depressive symptoms may help prevent suicide risk among young people exposed to housing exclusion.

Safety evaluation of kaempferol glycosides-rich standardized roasted goji berry leaf extract.

Goji berry leaf (GL) has been used for medicinal foods for its pharmacological effects, including anti-oxidative and anti-obesity activities. Nevertheless, toxicological information on GL is limited for developing health functional ingredient. The aim of the research was to evaluate the single dose acute, 14-day repeated oral toxicity, and genotoxicity of standardized roasted GL extract (rGL) rich in kaempferol-3-O-sophoroside-7-O-glucoside. Tested rGL was found to be stable as kaempferol-3-O-sophoroside-7-O-glucoside, showing 0.7-2.1% of analytical standard variance. According to the single dose toxicity for 14 days, the lethal dose of rGL was determined to be ≥ 2000 mg/kg. Repeated doses of 0-1000 mg/kg of rGL per day for 14 days did not show any toxicity signs or gross pathological abnormalities. No genotoxic signs for the rGL treatment appeared via bacterial reverse mutation up to 5000 µg/plate. There was no significant increase in chromosomal aberration of rGL irrespective of metabolic activation by using CHO-K1 cells (p > 0.05). Regarding carcinogenic toxicity, chromosomal aberrations were not induced at 2000 mg of rGL/kg by using the in vivo bone marrow micronucleus test (p > 0.05). Results from the current study suggest that rGL could be used as a functional ingredient to provide various effects with safety assurance.

Drug-Eluting Bead Transarterial Chemoembolization Versus Radiofrequency Ablation as an Initial Treatment of Single Small (≤ 3 cm) Hepatocellular Carcinoma.

BACKGROUND: In this study, we aimed to compare the long-term therapeutic outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) with those of radiofrequency ablation (RFA) for the initial treatment of a single small (≤ 3 cm) hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2021, 259 consecutive patients who underwent DEB-TACE (67 patients) or RFA (192 patients) as a first-line treatment for a single small HCC were enrolled in this retrospective study. The therapeutic outcomes, including cumulative intrahepatic local tumor progression (LTP), progression-free survival (PFS), and long-term overall survival (OS) rates, were compared between the two groups before and after propensity score (PS) matching. Multivariate Cox proportional hazard models were used to evaluate the prognostic factors and differences in OS and PFS between the two groups for all 92 patients after PS matching. RESULTS: After PS matching, the 1-, 2-, 3-, and 5-year LTP rates were lower in the RFA group than those in the DEB-TACE group (P < 0.001), and the 1-, 2-, 3-, and 5-year PFS rates in the RFA group were higher than those in the DEB-TACE group (P = 0.007). However, the 1-, 2-, 3-, and 5-year OS rates were not significantly different between the RFA and DEB-TACE groups (P = 0.584). Moreover, the OS was not significantly different between the RFA and DEB-TACE groups in the univariate and multivariate analyses, with a hazard ratio (HR) of 0.81. The PFS was significantly higher in the RFA group than that in the DEB-TACE group in the univariate analyses, with a HR of 0.44 (P = 0.009). Multivariate Cox regression analysis showed that albumin (P = 0.019) was an independent prognostic factor for OS. Additionally, the major complication rates were not significantly different between the DEB-TACE and RFA groups (P = 1.000). CONCLUSION: The LTP and PFS rates of RFA were superior to those of DEB-TACE in the initial treatment of single small HCC after PS matching. However, the OS rates were not significantly different between RFA and DEB-TACE. Therefore, DEB-TACE may be considered an efficient substitute for RFA in some patients with a single small HCC who are ineligible for RFA.

Optical Penetration of Shape-Controlled Metallic Nanosensors across Membrane Barriers.

Precise nanostructure geometry that enables the optical biomolecular delivery of nanosensors to the living intracellular environment is highly desirable for precision biological and clinical therapies. However, the optical delivery through membrane barriers utilizing nanosensors remains difficult due to a lack of design guidelines to avoid inherent conflict between optical force and photothermal heat generation in metallic nanosensors during the process. Here, we present a numerical study reporting significantly enhanced optical penetration of nanosensors by engineering nanostructure geometry with minimized photothermal heating generation for penetrating across membrane barriers. We show that by varying the nanosensor geometry, penetration depths can be maximized while heat generated during the penetration process can be minimized. We demonstrate the effect of lateral stress induced by an angularly rotating nanosensor on a membrane barrier by theoretical analysis. Furthermore, we show that by varying the nanosensor geometry, maximized local stress fields at the nanoparticle-membrane interface enhanced the optical penetration process by four-fold. Owing to the high efficiency and stability, we anticipate that precise optical penetration of nanosensors to specific intracellular locations will be beneficial for biological and therapeutic applications.

Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F.

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

Toxicological profile of bisphenol F via comprehensive and extensive toxicity evaluations following dermal exposure.

Bisphenol F (BPF) is classified as a harmful substance by the U.S. Environmental Protection Agency. Although previous studies focused on human exposure to BPF via direct consumption or inhalation, few investigators assessed potential toxicological effects following skin contact. The aim of this study was to examine (1) the degree and pattern by which BPF is absorbed onto the skin in vivo, and (2) determination of toxicity and safety using the following tests: acute dermal; a 28-day repeat dermal; a skin irritation; an eye irritation; and a skin sensitization. As indicated by the amount of BPF remaining in the epidermis or dermis, data demonstrated that BPF was absorbed through the skin at a 26.5% rate. BPF penetrated the subcutaneous layer at a "fast rate" (Kp: 2.2E-02). Although no toxicological changes or local irritation were observed following skin exposure, BPF induced potent sensitization. In summary, the findings of this study showed that BPF penetrated and was absorbed into the skin at a high rate which was associated with enhanced chemical-induced skin sensitization and this may have significant implications following exposure of skin to BPF.

Intelligent Fusion Imaging Photonics for Real-Time Lighting Obstructions.

Dynamic detection in challenging lighting environments is essential for advancing intelligent robots and autonomous vehicles. Traditional vision systems are prone to severe lighting conditions in which rapid increases or decreases in contrast or saturation obscures objects, resulting in a loss of visibility. By incorporating intelligent optimization of polarization into vision systems using the iNC (integrated nanoscopic correction), we introduce an intelligent real-time fusion algorithm to address challenging and changing lighting conditions. Through real-time iterative feedback, we rapidly select polarizations, which is difficult to achieve with traditional methods. Fusion images were also dynamically reconstructed using pixel-based weights calculated in the intelligent polarization selection process. We showed that fused images by intelligent polarization selection reduced the mean-square error by two orders of magnitude to uncover subtle features of occluded objects. Our intelligent real-time fusion algorithm also achieved two orders of magnitude increase in time performance without compromising image quality. We expect intelligent fusion imaging photonics to play increasingly vital roles in the fields of next generation intelligent robots and autonomous vehicles.

Ultraprecision Imaging and Manipulation of Plasmonic Nanostructures by Integrated Nanoscopic Correction.

Optical manipulation and imaging of nano-objects with nanometer precision is highly desirable for nanomaterial and biological studies due to inherent noninvasiveness. However, time constraints and current segregated experimental systems for nanoimaging and nanomanipulation limits real-time super-resolution imaging with spatially enhanced manipulation. Here, an integrated nanoscopic correction (iNC) method to enable multimodal nanomanipulation-nanoimaging is reported. The iNC consists of a multimodal voltage-tunable power modulator, polarization rotator, and polarizer. Using the iNC, plasmonic nano-objects which are below the diffraction limit and which can be distinguished by direct observation without post processing are demonstrated. Furthermore, such direct observations with enhanced nanometer spatial stability and millisecond high speed are shown. Precise trapping and rapid rotation of gold nanorods with the iNC are demonstrated successfully. With non-invasive post-processing free nanoimaging and nanomanipulation, it is anticipated that the iNC will make contributions in the nanomaterial and biological sciences requiring precision optics.

Visible-Light Induced Sustainable Water Treatment Using Plasmo-Semiconductor Nanogap Bridge Array, PNA.

The development of sustainable methods for energy-intensive water treatment processes continues to be a challenging issue. Plasmonic-semiconductor nanoparticles, which absorb large amounts of sunlight in the visible range for conversion into chemical energy efficiently, can form the basis of a sustainable water treatment method. However, the potential uses of plasmonic semiconductor particles for water treatment have not been fully explored yet because of the limitations associated with the imbalance between light capture, charge transfer, and the required recycling steps for the particles themselves. Herein, a significantly improved visible-light-induced water treatment method that uses a plasmo-semiconductor nanogap bridge array (PNA) is reported. As an arrangement of antenna-reactors, the PNA enables the balancing of the largely enhanced electromagnetic field in the plasmonic nanogap coupling region and optimal separation of charge carriers in the semiconductor. The simultaneous effects of visible-light absorption and charge transfer lead to the generation of a highly enhanced visible-light-induced OH radical (•OH). Consequently, visible-light-induced 5-log N/N0 water disinfection and 100% chemical decomposition for sustainable water treatment were demonstrated. Owing to the large light absorption, charge carrier utilization, and array-oriented scalability, the PNA will be valuable in various sustainable energy and environmental applications.

Promoter engineering-mediated Tuning of esterase and transaminase expression for the chemoenzymatic synthesis of sitagliptin phosphate at the kilogram-scale.

Here, we report a bienzymatic cascade to produce ß-amino acids as an intermediate for the synthesis of the leading oral antidiabetic drug, sitagliptin. A whole-cell biotransformation using recombinant Escherichia coli coexpressing a esterase and transaminase were developed, wherein the desired expression level of each enzyme was achieved by promotor engineering. The small-scale reactions (30 ml) performed under optimized conditions at varying amounts of substrate (100-300 mM) resulted in excellent conversions of 82%-95% for the desired product. Finally, a kilogram-scale enzymatic reaction (250 mM substrate, 220 L) was carried out to produce ß-amino acid (229 mM). Sitagliptin phosphate was chemically synthesized from ß-amino acids with 82% yield and > 99% purity.

Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats.

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.

Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice.

Wild ginseng has better pharmacological effects than cultivated ginseng. However, its industrialization is limited by the inability to grow wild ginseng on a large scale. Herein, we demonstrate how to optimize ginseng production through cultivation, and how to enhance the concentrations of specific ginsenosides through fermentation. In the study, we also evaluated the ability of fermented cultured wild ginseng root extract (HLJG0701-ß) to inhibit acetylcholinesterase (AChE), as well as its neuroprotective effects and antioxidant activity. In invitro tests, HLJG0701-ß inhibited AChE activity and exerted neuroprotective and antioxidant effects (showing increased catalyst activity but decreased reactive oxygen species concentration). In invivo tests, after HLJG0701-ß was orally administered at doses of 0, 125, 250, and 500 mg/kg in an animal model of memory impairment, behavioral evaluation (Morris water maze test and Y-maze task test) was performed. The levels of AChE, acetylcholine (ACh), blood catalase (CAT), and malondialdehyde (MDA) in brain tissues were measured. The results showed that HLJG0701-ß produced the best results at a dose of 250 mg/kg or more. The neuroprotective mechanism of HLJG0701-ß was determined to involve the inhibition of AChE activity and a decrease in oxidative stress. In summary, both invitro and invivo tests confirmed that HJG0701-ß administration can lead to memory improvement.

3D brain angiogenesis model to reconstitute functional human blood-brain barrier in vitro.

The human central nervous system (CNS) vasculature expresses a distinctive barrier phenotype, the blood-brain barrier (BBB). As the BBB contributes to low efficiency in CNS pharmacotherapy by restricting drug transport, the development of an in vitro human BBB model has been in demand. Here, we present a microfluidic model of CNS angiogenesis having three-dimensional (3D) lumenized vasculature in concert with perivascular cells. We confirmed the necessity of the angiogenic tri-culture system (brain endothelium in direct interaction with pericytes and astrocytes) to attain essential phenotypes of BBB vasculature, such as minimized vessel diameter and maximized junction expression. In addition, lower vascular permeability is achieved in the tri-culture condition compared to the monoculture condition. Notably, we focussed on reconstituting the functional efflux transporter system, including p-glycoprotein (p-gp), which is highly responsible for restrictive drug transport. By conducting the calcein-AM efflux assay on our 3D perfusable vasculature after treatment of efflux transporter inhibitors, we confirmed the higher efflux property and prominent effect of inhibitors in the tri-culture model. Taken together, we designed a 3D human BBB model with functional barrier properties based on a developmentally inspired CNS angiogenesis protocol. We expect the model to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.

Meiobenthic nematodes in the assessment of the relative impact of human activities on coastal marine ecosystem.

Ecological quality (EcoQ) status of the Southwest and West coasts of South Korea was evaluated within the "National Investigation of Marine Ecosystems in Korea" in the 2015. In particular, the study dealt to assess the ecological quality of the sediments using free-living nematode communities. A total of 149 species were found in the study area, and Daptonema, Sabatieria, Parodontophora, Sphaerolaimus, and Viscosia were found as dominant genera. Statistical analysis of both environmental and faunal parameters showed an increasing human pressure from Western to Southern coasts. The community structure changed with the environmental features of the study area and allowed the detection of a suite of possible nematode indicators that might be used in monitoring studies. In particular, Dorylaimopsis spp. appeared heavy metal and organic matter resistant taxa, Sabatieria an eutrophication resistant genus, while Paracanthonchus and Neotonchus as heavy metal and organic matter sensitive genera. The principal component analysis (PCA) results showed a clear negative correlation between maturity index and both heavy metal and organic matter increasing, while diversity indices did not appear to be significantly influenced by them. Appling the thresholds of the synthetic nematode indices, the EcoQ of the study area was assessed as poor to moderate.

Role of paroxysmal depolarization in focal seizure activity.

We analyze the role of inhibition in sustaining focal epileptic seizure activity. We review ongoing seizure activity at the mesoscopic scale that can be observed with microelectrode arrays as well as at the macroscale of standard clinical EEG. We provide clinical, experimental, and modeling data to support the hypothesis that paroxysmal depolarization (PD) is a critical component of the ictal machinery. We present dual-patch recordings in cortical cultures showing reduced synaptic transmission associated with presynaptic occurrence of PD, and we find that the PD threshold is cell size related. We further find evidence that optically evoked PD activity in parvalbumin neurons can promote propagation of neuronal excitation in neocortical networks in vitro. Spike sorting results from microelectrode array measurements around ictal wave propagation in human focal seizures demonstrate a strong increase in putative inhibitory firing with an approaching excitatory wave, followed by a sudden reduction of firing at passage. At the macroscopic level, we summarize evidence that this excitatory ictal wave activity is strongly correlated with oscillatory activity across a centimeter-sized cortical network. We summarize Wilson-Cowan-type modeling showing how inhibitory function is crucial for this behavior. Our findings motivated us to develop a network motif of neurons in silico, governed by a reduced version of the Hodgkin-Huxley formalism, to show how feedforward, feedback, PD, and local failure of inhibition contribute to observed dynamics across network scales. The presented multidisciplinary evidence suggests that the PD not only is a cellular marker or epiphenomenon but actively contributes to seizure activity.NEW & NOTEWORTHY We present mechanisms of ongoing focal seizures across meso- and macroscales of microelectrode array and standard clinical recordings, respectively. We find modeling, experimental, and clinical evidence for a dual role of inhibition across these scales: local failure of inhibition allows propagation of a mesoscopic ictal wave, whereas inhibition elsewhere remains intact and sustains macroscopic oscillatory activity. We present evidence for paroxysmal depolarization as a mechanism behind this dual role of inhibition in shaping ictal activity.

Weavable and Highly Efficient Organic Light-Emitting Fibers for Wearable Electronics: A Scalable, Low-Temperature Process.

Fiber-based wearable displays, one of the most desirable requisites of electronic textiles (e-textiles), have emerged as a technology for their capability to revolutionize textile and fashion industries in collaboration with the state-of-the-art electronics. Nonetheless, challenges remain for the fibertronic approaches, because fiber-based light-emitting devices suffer from much lower performance than those fabricated on planar substrates. Here, we report weavable and highly efficient fiber-based organic light-emitting diodes (fiber OLEDs) based on a simple, cost-effective and low-temperature solution process. The values obtained for the fiber OLEDs, including efficiency and lifetime, are similar to that of conventional glass-based counterparts, which means that these state-of-the-art, highly efficient solution processed planar OLEDs can be applied to cylindrical shaped fibers without a reduction in performance. The fiber OLEDs withstand tensile strain up to 4.3% at a radius of 3.5 mm and are verified to be weavable into textiles and knitted clothes by hand-weaving demonstrations. Furthermore, to ensure the scalability of the proposed scheme fiber OLEDs with several diameters of 300, 220, 120, and 90 µm, thinner than a human hair, are demonstrated successfully. We believe that this approach, suitable for cost-effective reel-to-reel production, can realize low-cost commercially feasible fiber-based wearable displays in the future.

Vasorelaxant Effect of Prunus mume (Siebold) Siebold & Zucc. Branch through the Endothelium-Dependent Pathway.

Korean plum (Prunus mume (Siebold) Siebold & Zucc.) has long been used as a health food or herbal medicine in Asia. Previous studies have shown that several plants of the genus Prunus have vasodilatory and antihypertensive effects; we hypothesized that P. mume branches may have a vasorelaxant effect. In this study, we evaluated the effects and action mechanism of 70% ethanol extract of P. mume branch (PMB) on isolated rat aortic rings. Inhibitors such as NG-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, methylene blue, indomethacin, atropine, tetraethylammonium chloride, glibenclamide, 4-aminopyridine and BaCl2 were used to investigate the mechanism of vasodilation responsible for the vascular relaxation. PMB (2-30 µg/mL) induced vasorelaxation in the presence of vascular endothelium, and all inhibitors used in this study affected the degree of relaxation. These results suggest that the vasorelaxant effect of PMB is endothelium-dependent and affects the nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin pathway, muscarinic receptor pathway, and potassium channels. Our study explains that PMB may be another approach to hypertension treatment to reduce the burden of cardiovascular disease.