Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Correction to: Application of Schizosaccharomyces japonicus in makgeolli fermentation and its brewing characteristics.

[This corrects the article DOI: 10.1007/s10068-023-01265-6.].

Correction: The Effect of an mHealth Self-Monitoring Intervention (MI-BP) on Blood Pressure Among Black Individuals With Uncontrolled Hypertension: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/57863.].

Citrullus mucosospermus Extract Exerts Protective Effects against Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Steatohepatitis in Mice.

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

Citrullus mucosospermus Extract Reduces Weight Gain in Mice Fed a High-Fat Diet.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

The Effect of an mHealth Self-Monitoring Intervention (MI-BP) on Blood Pressure Among Black Individuals With Uncontrolled Hypertension: Randomized Controlled Trial.

BACKGROUND: Hypertension is one of the most important cardiovascular disease risk factors and affects >100 million American adults. Hypertension-related health inequities are abundant in Black communities as Black individuals are more likely to use the emergency department (ED) for chronic disease-related ambulatory care, which is strongly linked to lower blood pressure (BP) control, diminished awareness of hypertension, and adverse cardiovascular events. To reduce hypertension-related health disparities, we developed MI-BP, a culturally tailored multibehavior mobile health intervention that targeted behaviors of BP self-monitoring, physical activity, sodium intake, and medication adherence in Black individuals with uncontrolled hypertension recruited from ED and community-based settings. OBJECTIVE: We sought to determine the effect of MI-BP on BP as well as secondary outcomes of physical activity, sodium intake, medication adherence, and BP control compared to enhanced usual care control at 1-year follow-up. METHODS: We conducted a 1-year, 2-group randomized controlled trial of the MI-BP intervention compared to an enhanced usual care control group where participants aged 25 to 70 years received a BP cuff and hypertension-related educational materials. Participants were recruited from EDs and other community-based settings in Detroit, Michigan, where they were screened for initial eligibility and enrolled. Baseline data collection and randomization occurred approximately 2 and 4 weeks after enrollment to ensure that participants had uncontrolled hypertension and were willing to take part. Data collection visits occurred at 13, 26, 39, and 52 weeks. Outcomes of interest included BP (primary outcome) and physical activity, sodium intake, medication adherence, and BP control (secondary outcomes). RESULTS: We obtained consent from and enrolled 869 participants in this study yet ultimately randomized 162 (18.6%) participants. At 1 year, compared to the baseline, both groups showed significant decreases in systolic BP (MI-BP group: 22.5 mm Hg decrease in average systolic BP and P<.001; control group: 24.1 mm Hg decrease and P<.001) adjusted for age and sex, with no significant differences between the groups (time-by-arm interaction: P=.99). Similar patterns where improvements were noted in both groups yet no differences were found between the groups were observed for diastolic BP, physical activity, sodium intake, medication adherence, and BP control. Large dropout rates were observed in both groups (approximately 60%). CONCLUSIONS: Overall, participants randomized to both the enhanced usual care control and MI-BP conditions experienced significant improvements in BP and other outcomes; however, differences between groups were not detected, speaking to the general benefit of proactive outreach and engagement focused on cardiometabolic risk reduction in urban-dwelling, low-socioeconomic-status Black populations. High dropout rates were found and are likely to be expected when working with similar populations. Future work is needed to better understand engagement with mobile health interventions, particularly in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02955537; https://clinicaltrials.gov/study/NCT02955537. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/12601.

Healthcare Professionals' Learning Needs and Perspectives on Essential Information in Genetic Cancer Care: A Systematic Review.

BACKGROUND: The increased demand for genetic testing and counseling necessitates healthcare professionals (HCPs) to improve their genetic competency through training programs. This systematic review identified HCPs' learning needs and their perspectives on essential information for families with hereditary cancer. METHODS: This review covered studies published from 2013 to 2024 across five databases. Data were analyzed using a content analysis. RESULTS: Thirteen studies involving 332 HCPs were analyzed. Most studies focused on the learning needs of physicians caring for families affected by Hereditary Breast and Ovarian Cancer in North America and Europe. HCPs required training emphasizing practical counseling skills over the basics of genetics. Learning needs varied by profession: physicians needed training in assessing cancer risk and supporting decision-making in risk management; nurses required information on resources and the genetic care system; genetic counselors sought guidance on family communication and planning. Essential information identified for families included risk-reducing strategies, personalized cancer risk assessment, family implications, psychological issues, (cascade) genetic testing, and social concerns. CONCLUSIONS: The findings have implications for the development of training programs for HCPs, emphasizing the need for tailored training based on professions. Future research should explore the needs of HCPs caring for families with diverse hereditary cancers and cultural backgrounds.

Identifying Interventions to Improve Diagnostic Safety in Emergency Departments: Protocol for a Participatory Design Study.

BACKGROUND: Emergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks. OBJECTIVE: This study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and involve them in co-designing technological interventions to enhance diagnostic excellence. METHODS: We will conduct separate sessions with ED health care providers and patients, respectively, to assess various design ideas and use a participatory design (PD) approach for technological interventions to improve ED diagnostic safety. In the sessions, various intervention ideas will be presented to participants through storyboards. Based on a preliminary interview study with ED patients and health care providers, we created intervention storyboards that illustrate different care contexts in which ED health care providers or patients experience challenges and show how each intervention would address the specific challenge. By facilitating participant group discussion, we will reveal the overlap between the needs of the design research team observed during fieldwork and the needs perceived by target users (ie, participants) in their own experience to gain their perspectives and assessment on each idea. After the group discussions, participants will rank the ideas and co-design to improve our interventions. Data sources will include audio and video recordings, design sketches, and ratings of intervention design ideas from PD sessions. The University of Michigan Institutional Review Board approved this study. This foundational work will help identify the needs and challenges of key stakeholders in the ED diagnostic process and develop initial design ideas, specifically focusing on sociotechnological ideas for patient-, health care provider-, and system-level interventions for improving patient safety in EDs. RESULTS: The recruitment of participants for ED health care providers and patients is complete. We are currently preparing for PD sessions. The first results from design sessions with health care providers will be reported in fall 2024. CONCLUSIONS: The study findings will provide unique insights for designing sociotechnological interventions to support ED diagnostic processes. By inviting frontline health care providers and patients into the design process, we anticipate obtaining unique insights into the ED diagnostic process and designing novel sociotechnical interventions to enhance patient safety. Based on this study's collected data and intervention ideas, we will develop prototypes of multilevel interventions that can be tested and subsequently implemented for patients, health care providers, or hospitals as a system. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55357.

Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing ligand.

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH.

PVA Hydrogels Supplemented with PLA Mesh for Tissue Regeneration Scaffold.

This study examined the tensile strength and biocompatibility properties of polyvinyl alcohol (PVA) hydrogel tissue regeneration scaffolds with polylactic acid (PLA) mesh fabric added as reinforcement, with a focus on the impact of heat treatment temperature and the number of layers of the PLA mesh fabric. The hydrogel scaffolds were prepared using a freeze-thaw method to create PVA hydrogel, with the PLA mesh fabric placed inside the hydrogel. The swelling ratio of the PVA/PLA hydrogel scaffolds decreased with increasing layer number and heat treatment temperature of the PLA mesh. The gel strength was highest when five layers of PLA mesh fabric were added, heat-treated at 120 °C, and confirmed to be properly placed inside the hydrogel by SEM images. The MTT assay and DAPI staining using HaCaT cells demonstrated that the cell proliferation was uninterrupted throughout the experimental period, confirming the biocompatibility of the scaffold. Therefore, we confirmed the possibility of using PLA mesh fabric as a reinforcement for PVA hydrogel to improve the strength of scaffolds for tissue regeneration, and we confirmed the potential of PLA mesh fabric as a reinforcement for various biomaterials.

Strain-invariant stretchable radio-frequency electronics.

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression.

Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in ob/ob mice. The TAT38 (a.a. 20-57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20-35 TACTNCYCAKCCFQVC), core-domain (a.a. 36-46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47-57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4-11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.

Simultaneous detection of residues of 34 beta-lactam antibiotics in livestock and fish samples through liquid chromatography-tandem mass spectrometry.

ß-Lactam is one of the widely used veterinary drugs, but simultaneous analytical methods for ß-lactam on various animal foods have not been established. In this study, we aimed to detect 34 ß-lactam antibiotics simultaneously in livestock samples (beef, pork, chicken, egg, and milk) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Samples were extracted using phosphate buffer/acetonitrile or water/acetonitrile and then cleaned with 150 mg of C18 and 900 mg of MgSO4. The method showed acceptable recovery and repeatability of 66.1-119% and 1.5-26%, respectively. The method was employed to monitor 127 real samples from the domestic market to confirm its applicability, and no ß-lactam residues were detected. It was also applied to other matrices (eel, flat fish, and shrimp) and showed acceptable recovery (62.1-120%) and repeatability (1.0-28%). The method is expected to improve the efficiency of monitoring veterinary drug residues in domestic livestock products and fishery foods.

Calcium Chloride as a Novel Stabilizer for Foot-and-Mouth Disease Virus and Its Application in the Vaccine Formulation.

The thermal stability of the in-house-developed foot-and-mouth disease (FMD) type O and A viruses was evaluated, and the O Jincheon virus was found to exhibit the lowest thermal stability. To overcome this instability, we proposed a novel stabilizer, calcium chloride. The thermal stability of FMDVs increased up to a CaCl2 concentration of 10 mM, and it had a decreasing trend at >30 mM. The O Jincheon virus showed a significant decrease in the amount of antigen over time at 4 °C. In contrast, the samples treated with CaCl2 showed stable preservation of the virus without significant antigen loss. After the CaCl2-formulated vaccine was administered twice to pigs, the virus neutralization titer reached approximately 1:1000, suggesting that the vaccine could protect pigs against the FMDV challenge. In summary, the O Jincheon virus is difficult to utilize as a vaccine given its low stability during storage after antigen production. However, following its treatment with CaCl2, it can be easily utilized as a vaccine. This study evaluated CaCl2 as a novel stabilizer in FMD vaccines and may contribute to the development of stable vaccine formulations, especially for inherently unstable FMDV strains.

Impact of Prospero Homeobox-1 (PROX-1) οn the Oncogenic Phenotypes of Hepatocellular Carcinoma Cells.

BACKGROUND/AIM: Transcriptional factor prospero homeobox-1 (PROX-1) is crucial for the embryonic development of various organs and cell fate specification. It exhibits either an oncogenic or tumor suppressive activity depending on cancer types. However, the relationship between PROX-1 and hepatocellular carcinoma (HCC) remains obscure. This study was conducted to investigate the effect of PROX-1 on the invasive and oncogenic phenotypes of human HCC cells. MATERIALS AND METHODS: The effect of PROX-1 on tumor cell behavior was investigated by using a pcDNA-myc vector and a small interfering RNA in HepG2 and Huh7 human HCC cell lines. Flow cytometry, migration, invasion, proliferation, and tube formation assays were performed. PROX-1 expression in human HCC cells was explored by western blotting. RESULTS: PROX-1 overexpression enhanced tumor cell proliferation and inhibited apoptosis and cell cycle arrest by modulating the activities of caspase-3, PARP, and cyclin-dependent kinase inhibitors, including p21, p27, and p57 in HCC cells. After PROX-1 overexpression, the number of migrating and invading HCC cells significantly increased, and the expression levels of N-cadherin and Snail increased in HCC cells. PROX-1 overexpression enhanced angiogenesis through increased VEGF-A and VEGF-C expression and decreased angiostatin expression. PROX-1 overexpression also increased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and forkhead box O1 (FOXO1) in HCC cells. After PROX-1 knockdown, their phosphorylation was reversed. CONCLUSION: PROX-1 overexpression is associated with the invasive and oncogenic phenotypes of human HCC cells via GSK-3ß and FOXO1 phosphorylation.

Determination of Optimal Antigen Yield and Virus Inactivation Conditions for the Production of the Candidate Foot-and-Mouth Disease Recombinant Vaccine Strain Asia1 Shamir-R in a Bioreactor.

Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010-2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 µg/mL, 5.2 µg/mL, and 3.8 µg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea.

Calcium Chloride Treatment Enhances Antigen Production in Foot-and-Mouth Disease Vaccines for Serotypes SAT1 and SAT3.

Foot-and-mouth disease (FMD) is a highly contagious viral infection causing acute and severe vesicular lesions in cattle and pigs, which has prompted global vaccination policies. This study presents a technique for enhancing antigen yield in SAT1 BOT and SAT3 ZIM by treatment with calcium chloride (CaCl2). We tested changes in cell viability in BHK-21 suspension cells treated with varying concentrations of CaCl2. The optimal CaCl2 concentration was determined based on antigen yield. The timing of CaCl2 supplementation relative to FMD virus inoculation was tested. Finally, the optimal medium for antigen production was identified. We observed a concentration-dependent decrease in BHK-21 cell viability at >7.5 mM CaCl2. A CaCl2 concentration of 3 mM yielded the most antigens. CaCl2 supplementation relative to FMD virus infection was optimal 2 h before or with viral inoculation. CD-BHK 21 medium supplemented with CaCl2 was the most productive medium. Specifically, SAT1 BOT and SAT3 ZIM showed improved antigen production in CD-BHK 21 medium with 3 mM CaCl2, while Provero-1 and Cellvento BHK-200 media showed no significant enhancement. Overall, CaCl2 supplementation enhanced FMD antigen productivity. This study provides a useful framework for enhancing antigen production efficiently in the FMD vaccine industry.

Stabilization of MOF (KAT8) by USP10 promotes esophageal squamous cell carcinoma proliferation and metastasis through epigenetic activation of ANXA2/Wnt signaling.

Dysregulation of MOF (also known as MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not catalytically inactive mutant (MOF-E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and deubiquitinates MOF at lysine 410, which protects it from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription in a JUN-dependent manner, which subsequently activates Wnt/ß-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.

Inhibition of Biofilm Formation in Cutibacterium acnes, Staphylococcus aureus, and Candida albicans by the Phytopigment Shikonin.

Skin microbiota, such as acne-related Cutibacterium acnes, Staphylococcus aureus, and fungal Candida albicans, can form polymicrobial biofilms with greater antimicrobial tolerance to traditional antimicrobial agents and host immune systems. In this study, the phytopigment shikonin was investigated against single-species and multispecies biofilms under aerobic and anaerobic conditions. Minimum inhibitory concentrations of shikonin were 10 µg/mL against C. acnes, S. aureus, and C. albicans, and at 1-5 µg/mL, shikonin efficiently inhibited single biofilm formation and multispecies biofilm development by these three microbes. Shikonin increased porphyrin production in C. acnes, inhibited cell aggregation and hyphal formation by C. albicans, decreased lipase production, and increased hydrophilicity in S. aureus. In addition, shikonin at 5 or 10 µg/mL repressed the transcription of various biofilm-related genes and virulence-related genes in C. acnes and downregulated the gene expression levels of the quorum-sensing agrA and RNAIII, α-hemolysin hla, and nuclease nuc1 in S. aureus, supporting biofilm inhibition. In addition, shikonin prevented multispecies biofilm development on porcine skin, and the antimicrobial efficacy of shikonin was recapitulated in a mouse infection model, in which it promoted skin regeneration. The study shows that shikonin inhibits multispecies biofilm development by acne-related skin microbes and might be useful for controlling bacterial infections.