Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Mitigation of Hearing Damage With Liraglutide Treatment in Chinchillas After Repeated Blast Exposures at Mild-TBI.

INTRODUCTION: Although hearing protection devices (HPDs) have been widely used during training and combat, over one million veterans experience service-connected hearing loss. Hearing damage has been reported to be associated with blast-induced mild traumatic brain injury (mTBI) and there is a lack of understanding and treatment. Liraglutide is a glucagon-like peptide-1 receptor agonist and a potential treatment for TBI-induced memory deficits. This study aims to investigate the function of the liraglutide to prevent damage and facilitate hearing restoration in chinchillas exposed to multiple high-intensity, mTBI-level blasts. MATERIALS AND METHODS: Chinchillas were divided into three treatment groups: blast control, pre-blast drug treatment, and post-blast drug treatment. On day 1, the chinchilla ears were protected by HPDs and exposed to three blasts with peak pressure levels of 15-25 psi. The auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) were recorded pre- and post-blast on day 1 and on days 4, 7, 14, and 28. RESULTS: Substantial acute damage was observed and progressively recovered in chinchillas after the blast exposures. The pre-blast treatment group exhibited the lowest elevation of the ABR threshold and reduction of the wave I amplitude on day 1 after blasts. The liraglutide treatment insignificantly facilitated the recovery of the DPOAE levels and ABR thresholds on days 14 and 28. The pre-blast treatment chinchillas showed reduced MLR amplitudes on days 4 and 7. CONCLUSIONS: This study indicated that the pre-blast liraglutide administration provided damage protection against blasts in addition to the HPDs. Current evidence suggests that the effect of liraglutide is more prominent in the early phase of the experiment.

The effects of rate pressure product at admission on cardiopulmonary function during hospitalization in patients with acute myocardial infarction.

OBJECTIVE: This study aimed to analyze the correlation between the rate pressure product (RPP) and cardiopulmonary function during hospitalization in patients with acute myocardial infarction (AMI). METHODS: A total of 362 patients with AMI were selected for the study, and the median admission RPP was used as the cutoff point to divide the patients into a low-RPP group (n = 181) and a high-RPP group (n = 181). The relationship between the RPP at admission and the cardiopulmonary function during hospitalization was analyzed. RESULTS: The patients in the high-RPP group had a higher body mass index (BMI) (p = 0.014), a higher prevalence of combined hypertension and diabetes mellitus (p < 0.001), a lower incidence of smoking (p = 0.044), and a higher incidence of oscillatory ventilation (6.1% vs. 1.7%, p = 0.029). The differences in RPP at rest, during warm-up, and within 1 and 4 minutes of recovery were statistically significant between the two groups (p < 0.01 on each occasion), while the differences in anaerobic threshold (AT) and watt max (Max) were not statistically significant (p > 0.05 for both). The patients in the low-RPP group had higher oxygen uptake (VO2 [AT]: 14.9 ± 3.4 vs. 14.2 ± 3.6, p = 0.048) and (VO2peak [Max]:18.2 ± 3.8 vs. 17.3 ± 3.8, p = 0.020). The RPP at admission was negatively correlated with VO2 (AT) and VO2peak (p < 0.05) using the regression Equation VO2peak = 33.682 + (-0.012 * RPP at admission/100) + (-0.105 * Age) + (-0.350 * BMI), while there was no correlation between the RPP at admission and VO2 (AT) (p = 0.149). CONCLUSION: The RPP at admission was negatively correlated with cardiopulmonary function during hospitalization in patients with AMI. Patients with a high RPP were more likely to have a combination of obesity, hypertension, diabetes mellitus, and reduced oxygen uptake during exercise, while a high RPP at admission appeared to affect their cardiovascular response indicators during exercise.

Synergistic Activation of Inert Iron Oxide Basal Planes through Heterostructure Formation and Doping for Efficient Hydrogen Evolution.

Iron oxides have emerged as a very promising and cost-effective alternative to precious metal catalysts for hydrogen production. However, the inert basal plane of iron oxides needs to be activated to enhance their catalytic efficiency. In this study, we employed heterostructure engineering and doped nickel to cooperatively activate the basal planes of iron oxide (Ni-Fe2 O3 /CeO2 HSs) to achieve high hydrogen evolution reaction (HER) activity. The Ni-Fe2 O3 /CeO2 HSs electrocatalyst demonstrates excellent basic HER activity and stability, such as an extremely low overpotential of 43 mV at 10 mA cm-2 current density and corresponding Tafel slope of 58.6 mV dec-1 . The increase in electrocatalyst activity and acceleration of hydrogen precipitation kinetics arises from the dual modulation of Ni doping and heterostructure, which not only modulates the electrocatalyst's electronic structure, but also increases the number and exposure of active sites. Remarkably, the generation of heterogeneous structure makes the catalyst se. The Ni-doped catalyst has not only increased HER activity but also low-temperature resistance. These results suggest that the synergistic activation of inert iron oxide basal planes through heterostructure formation and doping is a feasible strategy. Furthermore, for efficient electrocatalytic water splitting, this technique can be extended to other non-noble metal oxides.

Identification and validation of lactate metabolism-related genes in oxygen-induced retinopathy.

Retinopathy of Prematurity (ROP) is a multifactorial disease characterized by abnormal retinal vascular growth in premature infants, which is one of the leading causes of childhood blindness. Lactic acid metabolism may play an imperative role in the development of ROP, but there are still few relevant studies. Our team use a dataset GSE158799 contained 284 genes in 3 P17_OIR mice and 3 P30_OIR mice to identify 41 potentially differentially expressed lactate metabolism-related genes (LMRGs) related to ROP. Then through bioinformatics analysis, we strive to reveal the interaction, the enriched pathways and the immune cell infiltration among these LMRGs, and predict their functions and internal mechanisms. These DEGs may regulate lactate metabolism, leading to the changes of metabolism and immunity, thereby inducing the development of ROP. Our results will expand our understanding of the intrinsic mechanism of ROP and may be helpful for the directions for treatment of ROP in the future.

Therapeutic effect of demethylated hydroxylated phillygenin derivative on Helicobacter pylori infection.

Modifying and transforming natural antibacterial products is a novel idea for developing new efficacious compounds. Phillygenin has an inhibitory effect on H. pylori. The aim of the present study was to prepare a phillygenin derivative (PHI-Der) through demethylation and hydroxylation. The minimum inhibitory concentration of 18 strains of H. pylori from different sources was 8-32 µg/mL in vitro, and the activity increased 2-8 times than that of phillygenin. PHI-Der could significantly inhibit the colonization of H. pylori in vivo, reduce the inflammatory response, and promote the repair of inflammatory damage. Further, we used SwissTargetPrediction to predict that its main targets are ALOX5, MCL1, and SLC6A4, and find that it can inhibit bacterial biofilm formation and reduce bacterial infection of cells. It can enhance the intracellular oxidative capacity of H. pylori to inhibit H. pylori growth. Further, it could prevent the oxidation of H. pylori-infected cells and reduce the inflammatory response, which plays a role in protection. In conclusion, compared to phillygenin, PHI-Der had better antibacterial activity and was more effective in treating H. pylori infection. It has characteristics of high safety, specificity, resistance to drug resistance and better antibacterial activity than phillygenin, it's a good antioxidant for host cells.

3D Finite Element Model of Human Ear with 3-Chamber Spiral Cochlea for Blast Wave Transmission from the Ear Canal to Cochlea.

Blast-induced auditory trauma is a common injury in military service members and veterans that leads to hearing loss. While the inner ear response to blast exposure is difficult to characterize experimentally, computational models have advanced to predict blast wave transmission from the ear canal to the cochlea; however, published models have either straight or spiral cochlea with fluid-filled two chambers. In this paper, we report the recently developed 3D finite element (FE) model of the human ear mimicking the anatomical structure of the 3-chambered cochlea. The model consists of the ear canal, middle ear, and two and a half turns of the cochlea with three chambers separated by the Reissner's membrane (RM) and the basilar membrane (BM). The blast overpressure measured from human temporal bone experiments was applied at the ear canal entrance and the Fluent/Mechanical coupled fluid-structure interaction analysis was conducted in ANSYS software. The FE model-derived results include the pressure in the canal near the tympanic membrane (TM) and the intracochlear pressure at scala vestibuli, the TM displacement, and the stapes footplate (SFP) displacement, which were compared with experimentally measured data in human temporal bones. The validated model was used to predict the biomechanical response of the ear to blast overpressure: distributions of the maximum strain and stress within the TM, the BM displacement variation from the base to apex, and the energy flux or total energy entering the cochlea. The comparison of intracochlear pressure and BM displacement with those from the FE model of 2-chambered cochlea indicated that the 3-chamber cochlea model with the RM and scala media chamber improved our understanding of cochlea mechanics. This most comprehensive FE model of the human ear has shown its capability to predict the middle ear and cochlea responses to blast overpressure which will advance our understanding of auditory blast injury.

Real-time measurement of stapes motion and intracochlear pressure during blast exposure.

Blast-induced auditory injury is primarily caused by exposure to an overwhelming amount of energy transmitted into the external auditory canal, the middle ear, and then the cochlea. Quantification of this energy requires real-time measurement of stapes footplate (SFP) motion and intracochlear pressure in the scala vestibuli (Psv). To date, SFP and Psv have not been measured simultaneously during blast exposure, but a dual-laser experimental approach for detecting the movement of the SFP was reported by Jiang et al. (2021). In this study, we have incorporated the measurement of Psv with SFP motion and developed a novel approach to quantitatively measure the energy flux entering the cochlea during blast exposure. Five fresh human cadaveric temporal bones (TBs) were used in this study. A mastoidectomy and facial recess approach were performed to identify the SFP, followed by a cochleostomy into the scala vestibuli (SV). The TB was mounted to the "head block", a fixture to simulate a real human skull, with two pressure sensors - one inserted into the SV (Psv) and another in the ear canal near the tympanic membrane (P1). The TB was exposed to the blast overpressure (P0) around 4 psi or 28 kPa. Two laser Doppler vibrometers (LDVs) were used to measure the movements of the SFP and TB (as a reference). The LDVs, P1, and Psv signals were triggered by P0 and recorded simultaneously. The results include peak values for Psv of 100.8 ± 51.6 kPa (mean ± SD) and for SFP displacement of 72.6 ± 56.4 µm, which are consistent with published experimental results and finite element modeling data. Most of the P0 input energy flux into the cochlea occurred within 2 ms and resulted in 10-70 µJ total energy entering the cochlea. Although the middle ear pressure gain was close to that measured under acoustic stimulus conditions, the nonlinear behavior of the middle ear was observed from the elevated cochlear input impedance. For the first time, SFP movement and intracochlear pressure Psv have been successfully measured simultaneously during blast exposure. This study provides a new methodology and experimental data for determining the energy flux entering the cochlea during a blast, which serves as an injury index for quantifying blast-induced auditory damage.

Hearing protection and damage mitigation in Chinchillas exposed to repeated low-intensity blasts.

Repeated exposures to blast overpressure (BOP) introduce hearing complaints in military service members even with the use of hearing protection devices (HPDs). Although epidemiology and animal studies have been performed to investigate the damage formation mechanism of blast-induced hearing damage, there is still a lack of understanding and therapeutic solutions, especially for HPD-protected ears. Recent studies revealed the potential therapeutic function of liraglutide, a glucagon-like peptide-1 receptor agonist, to facilitate post-blast hearing restoration in chinchillas. This study is a continuation and summary of the previous studies performed by Jiang et al. (2021, 2022) to investigate the damage mitigation function of liraglutide treatment in chinchillas with open and protected ears after repeated low-intensity blast exposures within 28 days of observation. Chinchillas were divided into six experimental groups: pre-blast treatment, post-blast treatment, and blast control with ears open or protected by earplug (EP). All animals were exposed to six consecutive blasts at the level of 3-5 psi (21-35 kPa) on Day 1. Hearing function tests including auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) were performed on Day 1 (pre- and post-blast) and Days 4, 7, 14, and 28 after blast exposure. Results indicated that the damage mitigation function of the liraglutide treatment in the open-ear chinchillas was reflected by the significantly lower ABR threshold shifts in the drug treatment groups than in the blast controls. In EP groups, the higher ABR wave I/V ratio and lower MLR amplitude observed in the drug-treated chinchillas suggested that the post-blast hyperactivities in the auditory system might be potentially ameliorated by the liraglutide treatment. The 28-day-long experiment showed the effect of liraglutide treatment increased with time in both open and EP groups. This study demonstrated that the use of HPDs prevented the blast-induced complications in the middle ear and reduced the damage caused in the central auditory system. The liraglutide treatment showed an effect increasing with time and different outcomes in open and EP chinchillas. This innovation in the animal model of chinchilla provides insights to investigate subtle changes in the higher-level structures of the auditory system.

Preparation and hypoglycemic effects of chromium- and zinc-rich Acetobacter aceti.

BACKGROUND: At present, there is no ideal method to cure diabetes, and there are few reports on the treatment of diabetes with probiotics. AIM: To propose a method for preparing a new type of chromium- and zinc-rich Acetobacter aceti (A. aceti) and explore its ability to enhance the hypoglycemic effects of probiotics in the treatment of diabetes. METHODS: A. aceti was cultured in a liquid medium that contained chromium trichloride and zinc chloride, both at a concentration of 64 mg/mL, with the initial concentration of the bacterial solution 1 × 104 CFU/mL. After the bacterial solution had been inducted for 48 h, the culture media was changed and the induction was repeated once. The levels of chromium and zinc in the bacteria were detected by inductively coupled plasma mass spectrometry, and the contents of NADH and glucose dehydrogenase were determined using an NAD/NADH kit and glucose dehydrogenase kit, respectively. Streptozotocin was used to establish a mouse model to evaluate the hypoglycemic effects of the proposed chromium- and zinc-rich A. aceti. Ten-times the therapeutic dose was administered to evaluate its biological safety. The effect on MIN6 islet cells was also assessed in vitro. RESULTS: The levels of chromium metal, metallic zinc, NADH coenzyme, and glucose dehydrogenase in A. aceti prepared by this method were 28.58-34.34 mg/kg, 5.35-7.52 mg/kg, 5.13-7.26 µM, and 446.812-567.138 U/g, respectively. The use of these bacteria resulted in a better hypoglycemic effect than metformin, promoting the repair of tissues and cells of pancreatic islets in vivo and facilitating the growth of MIN6 pancreatic islet cells and increasing insulin secretion in vitro. Ten-times the therapeutic dose of treatment was non-toxic to mice. CONCLUSION: Chromium trichloride and zinc chloride can be employed to induce the preparation of chromium- and zinc-rich A. aceti, which can then promote the hypoglycemic effect found in normal A. aceti. The bacteria biotransforms the chromium and zinc in a way that could increase their safety as a treatment for diabetes.

Distinct Bile Acid Signature in Parkinson's Disease With Mild Cognitive Impairment.

Backgrounds: Bile acid (BA) plays a crucial role in various neurodegenerative diseases, including Parkinson's disease (PD). However, no clinical evidence supports BA's potential role in patients with PD with mild cognitive impairment (PD-MCI). Objectives: This study aimed at investigating the differential BA profile between patients with PD-MCI and those with normal cognitive function (PD-NC). Methods: Ultra-high performance liquid chromatography-MS/MS was applied for BA quantitation. After between-group differences of the BA profile were addressed, orthogonal projections to latent structures-discriminant analysis (OPLS-DA) and the area under the receiver-operating-characteristic curve (AUC-ROC) were implemented for further verification. Results: Lower levels of chenodeoxycholic acid (CDCA), cholic acid (CA), and ursodeoxycholic acid (UDCA) were significantly associated with PD-MCI (p < 0.01 for both; VIP ≈ 2.67, 1.66, and 1.26, respectively). AUC-ROC were 78.1, 74.2, and 74.5% for CDCA, CA, and UDCA, respectively. Conclusion: CA, CDCA, and UDCA might be distinct BA signatures for patients with PD-MCI.

Mitigation of Hearing Damage After Repeated Blast Exposures in Animal Model of Chinchilla.

High-intensity sound or blast-induced hearing impairment is a common injury for Service members. Epidemiology studies revealed that the blast-induced hearing loss is associated with the traumatic brain injury (TBI), but the mechanisms of the formation and prevention of auditory injuries require further investigation. Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been reported as a potential treatment strategy for TBI-caused memory deficits; however, there is no study on therapeutics of GLP-1R for blast-induced hearing damage. This paper reports our current study on progressive hearing damage after repeated exposures to low-level blasts in the animal model of chinchilla and the mitigation of hearing damage using liraglutide. Chinchillas were divided into three groups (N = 7 each): blast control, pre-blast treatment, and post-blast treatment. All animals were exposed to six consecutive blasts at the level of 3-5 psi (21-35 kPa) on Day 1. The auditory brainstem response (ABR) was measured on Day 1 (pre- and post-blast) and Days 4, 7, and 14 after blast exposure. Upon the completion of the experiment on Day 14, the brain tissues of animals were harvested for immunofluorescence studies. Significant damage was revealed in blast-exposed chinchillas by increased ABR thresholds, decreased ABR wave I amplitudes, and cell apoptosis in the inferior colliculus in the blast control chinchillas. Treatment with liraglutide appeared to reduce the severity of blast-induced hearing injuries as observed from the drug-treated chinchillas comparing to the blast controls. This study bridges the gap between TBI and hearing impairment and suggests a possible intervention for blast-induced hearing loss for Service members.

Linolenic Acid-Metronidazole: a Compound Relieving Drug Resistance and Inhibiting Helicobacter pylori.

Metronidazole (Met) is the first choice for treating Helicobacter pylori (Hp). However, Hp is easy to resistant, making Met unable to be widely used. How to overcome Hp's Met resistance is still an issue. In this study, Met was used as the primary raw material with linolenic acid to prepare a novel compound-linolenic acid-metronidazole (Lla-Met). The MIC, minimum bactericidal concentration (MBC), colonization amount of Hp in gastric mucosa, etc., were evaluated, respectively. Lla-Met was successfully prepared by the detection of nuclear magnetic resonance, etc., and its MIC and MBC to Hp were 2~4 µg/mL, 8~16 µg/mL. Moreover, in vivo experiments, Lla-Met significantly reduced the colonization of drug-resistant Hp in gastric mucosa. In the toxicity test, Lla-Met inhibited rate to GES-1 and BGC823 cells were 15% at 128 µg/mL; the mice were administered 10 times treatment Lla-Met treatment (240 mg/kg), have no difference significant injuries were found in their stomach, liver, spleen, kidney, and weight. In addition, Hp G27 continued for 18 days in vitro with sub-Lla-Met concentration, G27 did not show drug resistance to Lla-Met; Lla-Met did not exert an effect on non-Hp species with 128 µg/mL; Compared with a neutral environment, when the acid concentration is 3.0, Lla-Met is not decomposed and has better stability. Conclusion: Lla-Met, a newly prepared compound, has relatively well antibacterial of Met-resistant and sensitive Hp, with a capability of overcoming the metronidazole resistance of Hp.

Phillygenin Inhibits Helicobacter pylori by Preventing Biofilm Formation and Inducing ATP Leakage.

With the widespread use and abuse of antibiotics, Helicobacter pylori (H. pylori) has become seriously drug resistant. The development of new antibiotics is an important way to solve H. pylori's drug resistance. Screening antibacterial ingredients from natural products is a convenient way to develop new antibiotics. Phillygenin, an effective antibacterial component, was selected from the natural product, forsythia, in this study. Its minimal inhibitory concentration (MIC) for 18 H. pylori strains was 16-32 µg/ml. The minimum bactericidal concentration (MBC) of H. pylori G27 was 128 µg/ml; the higher the drug concentration and the longer the time, the better the sterilization effect. It was non-toxic to gastric epithelial cell (GES)-1 and BGC823 cells at the concentration of 100 µg/ml. It presented a better antibacterial effect on H. pylori in an acidic environment, and after 24 days of induction on H. pylori with 1/4 MIC of phillygenin, no change was found in the MIC of H. pylori. In the mechanism of action, phillygenin could cause ATP leakage and inhibit the biofilm formation; the latter was associated with the regulation of spoT and Hp1174 genes. In addition, phillygenin could regulate the genes of Nhac, caggamma, MATE, MdoB, flagellinA, and lptB, leading to the weakening of H. pylori's acid resistance and virulence, the diminishing of H. pylori's capacity for drug efflux, H. pylori's DNA methylation, the initiation of human immune response, and the ATP leakage of H. pylori, thus accelerating the death of H. pylori. In conclusion, phillygenin was a main ingredient inhibiting H. pylori in Forsythia suspensa, with a good antibacterial activity, high safety, strong specificity, better antibacterial effect under acidic conditions, and low risk of resistance development by H. pylori. Its mechanism of action was mainly associated with inhibiting the biofilm formation and resulting in ATP leakage. In addition, phillygenin was shown to be able to reduce the acid resistance and virulence of H. pylori.

Three-Dimensional Finite Element Modeling of Blast Wave Transmission From the External Ear to a Spiral Cochlea.

Blast-induced injuries affect the health of veterans, in which the auditory system is often damaged, and blast-induced auditory damage to the cochlea is difficult to quantify. A recent study modeled blast overpressure (BOP) transmission throughout the ear utilizing a straight, two-chambered cochlea, but the spiral cochlea's response to blast exposure has yet to be investigated. In this study, we utilized a human ear finite element (FE) model with a spiraled, two-chambered cochlea to simulate the response of the anatomical structural cochlea to BOP exposure. The FE model included an ear canal, middle ear, and two and half turns of two-chambered cochlea and simulated a BOP from the ear canal entrance to the spiral cochlea in a transient analysis utilizing fluid-structure interfaces. The model's middle ear was validated with experimental pressure measurements from the outer and middle ear of human temporal bones. The results showed high stapes footplate (SFP) displacements up to 28.5 µm resulting in high intracochlear pressures and basilar membrane (BM) displacements up to 43.2 µm from a BOP input of 30.7 kPa. The cochlea's spiral shape caused asymmetric pressure distributions as high as 4 kPa across the cochlea's width and higher BM transverse motion than that observed in a similar straight cochlea model. The developed spiral cochlea model provides an advancement from the straight cochlea model to increase the understanding of cochlear mechanics during blast and progresses toward a model able to predict potential hearing loss after blast.

A comprehensive finite element model for studying Cochlear-Vestibular interaction.

We present a 3-D finite element (FE) model of the chinchilla's inner ear consisting of the entire cochlea structure and the vestibular system. The reaction of the basilar membrane to the head rotation and the reaction of ampulla to the stapes movement were investigated. These results demonstrate the existence of hearing-vestibular system interaction. They provide an explanation to the clinical finding on the coexistence between hearing loss and equilibration dysfunction. It is a preliminary, yet critical step toward the development of a comprehensive FE model of an entire ear for mechano-acoustic analysis.

A 3D Printed Human Ear Model for Standardized Testing of Hearing Protection Devices to Blast Exposure.

Hypothesis: A 3D printed human temporal bone (TB) that is anatomically accurate would cost-effectively reproduce the responses observed in blast testing of human cadaveric TBs with and without passive hearing protection devices (HPDs). Background: HPDs have become critical personal protection equipment against auditory damage for service members. Acoustic test fixtures and human TBs have been used to test and develop HPDs; however, the lack of a cost-effective, standardized model impedes the improvement of HPDs. Methods: In this study, the 3D printed TB model was printed with flexible and rigid polymers and consisted of the ear canal, tympanic membrane (TM), ossicular chain, middle ear suspensory ligaments/muscle tendons, and middle ear cavity. The TM movement under acoustic stimulation was measured with laser Doppler vibrometry. The TB model was then exposed to blasts with or without HPDs and pressures at the ear canal entrance (P0) and near the TM in the ear canal (P1) were recorded. All results were compared with that measured in human TBs. Results: Results indicated that in the 3D printed TB, the attenuated peak pressures at P1 induced by HPDs ranged from 0.92 to 1.06 psi (170-171 dB) with blast peak pressures of 5.62-6.54 psi (186-187 dB) at P0, and measured results were within the mean and SD of published data. Vibrometry measurements also followed a similar trend as the published results. Conclusions: The 3D printed TB model accurately evaluated passive HPDs' protective function during blast and the potential for use as a model for acoustic transmission was investigated.

Accurately Locating Metastatic Foci in Lymph Nodes With Lugol's Iodine-Enhanced Micro-CT Imaging.

BACKGROUND: Accurate evaluation of lymph node (LN) status is the key factor to determine the treatment and evaluate prognosis for patients with cancer. However, traditional pathological examination resulted in a 30% false-negative rate of detection of metastases in LNs. This study aimed to utilize Lugol's iodine (I2-IK)-enhanced micro-CT imaging to reveal the 3-dimensional structure of regional LNs and decrease the false-negative rate in pathological examination. METHODS: To explore the feasibility of I2-IK-enhanced micro-CT imaging in locating metastatic lesion in LNs, nonmetastatic and metastatic LNs from mice were used to mimic the imaging process. Then, the LNs from oral squamous cell carcinoma (OSCC) patients were applied to verify the value of I2-IK-enhanced micro-CT imaging in revealing LN structure and locating metastatic lesions in LNs. The glycogen content in nonmetastatic and metastatic LNs was further detected by the use of a glycogen assay kit and periodic acid-Schiff (PAS) staining to explain the imaging differences between them. RESULTS: In nude mice, 0.5% I2-IK staining for 4 h was the best parameter for normal LN. The metastatic foci in metastatic LNs were also clearly outlined in this condition. For nonmetastatic LNs from patients with OSCC, 1% I2-IK staining for 12 h was the best parameter. However, due to the increased volume of metastatic LNs, the image effect of 3% I2-IK staining for 12 h was superior to 1% I2-IK staining [tumor background ratio (TBR), 3% vs. 1%, 1.89 ± 0.10 vs. 1.27 ± 0.07, p < 0.001]. Compared with subsequent pathological sections, we found the CT intensity of metastatic foci in LNs and muscle tissues was significantly higher than in nonmetastatic regions. Meanwhile, the glycogen content of metastatic foci in LNs detected was also significantly higher than in nonmetastatic region. CONCLUSIONS: I2-IK-enhanced micro-CT imaging could identify the spatial location of metastatic foci in LNs. This will be an effective method to assist in decreasing the LN false-negative rate for cancer pathology.

A novel 3D video oculography system for measuring cross-axis vestibulo-ocular reflex.

We present a video oculography (VOG) system with 6-degree-of-freedom (6-DOF) mobility for real-time measurements of the binocular 3D eye position of a small animal. A hybrid hexapod that allowed for multi-axis complex motions with the resolution of the microscopic level was used to control the motion of the animal. The instantaneous eyeball movement of the animal was determined based on two approaches: (1) tracking of marker arrays affixed to the cornea; and (2) tracking the pupil outline. The tracking of the eyeball movement and the motion control of the hexapod were implemented with the LabVIEW virtual instruments. Compared with our previous measurements using a servo-motor-based single-axis VOG system, positional error reduced from more than 4% to less than 0.7%. Validation showed that the tracking errors in three rotational axes are less than 2% for the magnitude and less than 5° for the direction angle. The present VOG system is an effective tool for cross-axis 3D vestibulo-ocular reflex study on small animals.