Epigenetic repression of CHCHD2 enhances survival from single cell dissociation through attenuated Rho A kinase activity.

During in vitro culture, human pluripotent stem cells (hPSCs) often acquire survival advantages characterized by decreased susceptibility to mitochondrial cell death, known as "culture adaptation." This adaptation is associated with genetic and epigenetic abnormalities, including TP53 mutations, copy number variations, trisomy, and methylation changes. Understanding the molecular mechanisms underlying this acquired survival advantage is crucial for safe hPSC-based cell therapies. Through transcriptome and methylome analysis, we discovered that the epigenetic repression of CHCHD2, a mitochondrial protein, is a common occurrence during in vitro culture using enzymatic dissociation. We confirmed this finding through genetic perturbation and reconstitution experiments in normal human embryonic stem cells (hESCs). Loss of CHCHD2 expression conferred resistance to single cell dissociation-induced cell death, a common stress encountered during in vitro culture. Importantly, we found that the downregulation of CHCHD2 significantly attenuates the activity of Rho-associated protein kinase (ROCK), which is responsible for inducing single cell death in hESCs. This suggests that hESCs may survive routine enzyme-based cell dissociation by downregulating CHCHD2 and thereby attenuating ROCK activity. These findings provide insights into the mechanisms by which hPSCs acquire survival advantages and adapt to in vitro culture conditions.

hTERT Peptide Fragment GV1001 Prevents the Development of Porphyromonas gingivalis-Induced Periodontal Disease and Systemic Disorders in ApoE-Deficient Mice.

GV1001, an anticancer vaccine, exhibits other biological functions, including anti-inflammatory and antioxidant activity. It also suppresses the development of ligature-induced periodontitis in mice. Porphyromonas gingivalis (Pg), a major human oral bacterium implicated in the development of periodontitis, is associated with various systemic disorders, such as atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the protective effects of GV1001 against Pg-induced periodontal disease, atherosclerosis, and AD-like conditions in Apolipoprotein (ApoE)-deficient mice. GV1001 effectively mitigated the development of Pg-induced periodontal disease, atherosclerosis, and AD-like conditions by counteracting Pg-induced local and systemic inflammation, partly by inhibiting the accumulation of Pg DNA aggregates, Pg lipopolysaccharides (LPS), and gingipains in the gingival tissue, arterial wall, and brain. GV1001 attenuated the development of atherosclerosis by inhibiting vascular inflammation, lipid deposition in the arterial wall, endothelial to mesenchymal cell transition (EndMT), the expression of Cluster of Differentiation 47 (CD47) from arterial smooth muscle cells, and the formation of foam cells in mice with Pg-induced periodontal disease. GV1001 also suppressed the accumulation of AD biomarkers in the brains of mice with periodontal disease. Overall, these findings suggest that GV1001 holds promise as a preventive agent in the development of atherosclerosis and AD-like conditions associated with periodontal disease.

GV1001 Inhibits the Severity of the Ligature-Induced Periodontitis and the Vascular Lipid Deposition Associated with the Periodontitis in Mice.

GV1001, a 16 amino acid peptide derived from the catalytic segment of human telomerase reverse transcriptase, was developed as an anti-cancer vaccine. Subsequently, it was found to exhibit anti-inflammatory and anti-Alzheimer's disease properties. Periodontitis is a risk factor for a variety of systemic diseases, including atherosclerosis, a process in which chronic systemic and vascular inflammation results in the formation of plaques containing lipids, macrophages, foam cells, and tissue debris on the vascular intima. Thus, we investigated the effect of GV1001 on the severity of ligature-induced periodontitis, vascular inflammation, and arterial lipid deposition in mice. GV1001 notably reduced the severity of ligature-induced periodontitis by inhibiting gingival and systemic inflammation, alveolar bone loss, and vascular inflammation in wild-type mice. It also significantly lowered the amount of lipid deposition in the arterial wall in ApoE-deficient mice receiving ligature placement without changing the serum lipid profile. In vitro, we found that GV1001 inhibited the Receptor Activator of NF-κB ligand (RANKL)-induced osteoclast formation and tumor necrosis factor-α (TNF-α)-induced phenotypic changes in endothelial cells. In conclusion, our study suggests that GV1001 prevents the exacerbation of periodontitis and atherosclerosis associated with periodontitis partly by inhibiting local, systemic, and vascular inflammation and phenotypic changes of vascular endothelial cells.

Cardiac Manifestations after Ingestion of a Commercial Desiccant: A Case Report.

Background and Objectives: The rise in suicidal attempts has led to an increase in unusual intoxication cases. The ingestion of anhydrous calcium chloride (CaCl2) causes direct injury to the gastrointestinal wall via a thermal burn. Therefore, previous reports on CaCl2 ingestion primarily considered the gastrointestinal injury. Severe CaCl2 intoxication can induce a hypercalcemic crisis, presenting with arrhythmia, acute pancreatitis, and acute kidney injury. This case report details a patient with hematemesis and hypercalcemia following the ingestion of a commercial desiccant. We aimed to report the progression of the case, with a focus on the electrocardiographic manifestations. Case Presentation: A 39-year-old female presented at a regional emergency center with blood in her vomit after the ingestion of a commercial desiccant. Bloody emesis was the initial symptom, and various electrolyte imbalances developed during admission. Electrocardiogram (ECG) changes occurred early after hospitalization and disappeared before the electrolyte levels normalized. The patient was maintained in an NPO (Nil Per Os) state throughout her hospital stay. The bloody emesis and abdominal pain resolved quite early, despite her minimal mention of symptoms, possibly due to her suspected negative psychiatric symptoms. Conclusions: In this case, we observed dynamic and prolonged multiple electrolyte imbalances along with the early-phase ECG changes, all of which responded well to supportive care. This report adds to the understanding of the diverse manifestations and management of CaCl2 intoxication.

Cholecalciferol- and α-tocopherol-loaded walnut oil emulsions stabilized by whey protein isolate and soy lecithin for food applications.

BACKGROUND: To overcome the limitations in the use of protein as an emulsifier, soy lecithin, a natural surfactant, was used along with whey protein isolate (WPI) to produce o/w emulsions containing cholecalciferol and α-tocopherol. The physical stability of the emulsions prepared with WPI and varying concentrations of lecithin (0, 1, 2, and 3% w/w) was measured in different heat, pH, and ionic-strength food environmental conditions. RESULTS: All emulsions were shown to be less than 250 nm in size and less than 0.3 in polydispersity index (PDI). The morphology of the emulsions was spherical, and the droplets of the emulsion containing lecithin were thicker and larger than those of the emulsion without lecithin (WPI_L0). After autoclaving, WPI_L0 increased in size from 197.8 ± 1.7 nm to 528.5 ± 28.4 nm, and the retention of cholecalciferol and α-tocopherol decreased to 40.83 ± 0.63% and 49.68 ± 1.84%, respectively. At pH 5.5, near the isoelectric point of WPI, WPI_L0 increased in size due to aggregation, but emulsions containing lecithin remained stable at a PDI under 0.3. Turbiscan stability index of the emulsion prepared with WPI and 3% lecithin was the lowest, indicating good storage stability. In addition, it was confirmed that the higher the lecithin content, the higher the viscosity, and the higher the amount of free fatty acids released in the in vitro digestion model. CONCLUSION: This study can provide theoretical evidence for enhancing the physical stability of protein emulsions by co-stabilization with lecithin, promoting their application in various foods. © 2022 Society of Chemical Industry.

Pancreas Involvement of Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type, Presenting as Acute Pancreatitis: A Case Report.

BACKGROUND: The main etiology of acute pancreatitis includes biliary origin and alcohol, although various other causes include drugs (i.e., L-asparaginase) or malignant tumors. Since accurate identification of etiologies is crucial for determining therapeutic planning, the assessment of cause should be performed as early as possible. CASE PRESENTATION: A 57-year-old Korean man was admitted for chemotherapy. The patient did not drink alcohol for religious reason. 26 days prior to admission, a 4 cm-sized testicular mass was observed in ultrasound and he received right radial orchiectomy. Extranodal natural killer/T-cell lymphoma, nasal type, was diagnosed. After confirming no additional abnormal findings, chemotherapy (using the regimens Dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) was begun. On Day 8 of chemotherapy, L-asparaginase was started and he complained of sudden onset epigastric pain after 2 days. Acute pancreatitis was diagnosed and, in order to determine if the acute pancreatitis occurred due to L-asparaginase or pancreas involvement of extranodal natural killer/T-cell lymphoma, endoscopic ultrasonography guided fine needle biopsy was performed and observed diffusely infiltrated tumor cells. Therefore, he was given a final diagnosis of acute pancreatitis due to pancreas involvement of extranodal natural killer/T-cell lymphoma, nasal type. DISCUSSION: Acute pancreatitis caused by pancreas involvement of extranodal natural killer/T-cell lymphoma, nasal type, is a very rare disease but can occur during chemotherapy. To identify the cause of acute pancreatitis, endoscopic ultrasonography guided fine needle biopsy can be considered.

Collateral Effect of the Coronavirus Disease 2019 Pandemic on Emergency Department Visits in Korea.

Background and Objectives: The ongoing coronavirus disease 2019 (COVID-19) pandemic represents a global public health crisis that has had a serious impact on emergency department (ED) utilization trends. The aim of this study was to investigate the collateral effects of the COVID-19 pandemic on ED utilization trends by patients with mild and severe conditions as well as on 7-day fatality rates. Materials and Methods: We analyzed entries in the Korean National Health Insurance claims database between 1 January 2018 and 31 December 2020. Six target patient groups were identified using the main diagnosis codes in the 10th revision of the International Classification of Diseases. Numbers of patients visiting the ED, their age, regional differences, 7-day fatality rate, and rate of emergency procedures were compared between 2018 and 2019 as the control period and 2020, when the COVID-19 pandemic was in full force. Results: During the 2020 COVID-19 pandemic, the number of patients who visited the ED with low-acuity diseases and severe acute respiratory infection diseases sharply decreased to −46.22% and −56.05%, respectively. However, the 7-day fatality rate after ED visits for low-acuity diseases and severe acute respiratory infection diseases increased to 0.04% (p < 0.01), and 1.65% (p < 0.01), respectively, in 2020 compared to that in the control period. Conclusions: During the 2020 COVID-19 pandemic, ED utilization impacted and 7-day fatality rate after ED visit increased. Health authorities and health care providers must strive to ensure prompt delivery of optimal care in EDs for patients with severe or serious symptoms and time-dependent diseases, even during the ongoing COVID-19 or potential future pandemics.

Comparison of COVID-19 Pandemic-Related Stress among Frontline Medical Personnel in Daegu City, Korea.

Background and Objectives: Frontline medical staff usually experience high levels of stress, which could greatly impact their work output. We conducted a survey to investigate the level of stress and its association with job types, work departments, and medical centers among COVID-19 pandemic frontline medical personnel. Materials and Methods: We conducted a cross-sectional survey using a self-administered questionnaire among 307 frontline medical staff who cared for COVID-19 patients in Daegu city. We used a 33-item questionnaire to assess respondents' general characteristics, job stress, personal effects associated with the COVID-19 pandemic, and their stress level. A general health questionnaire-12 (GHQ-12) was included in our questionnaire. Results: Majority (74.3%) of the respondents were in the stress group. The mean GHQ-12 score was 14.31 ± 4.96. More females (67.4%, p < 0.05) and nurses (73.3%, p = 0.001) were in the stress group compared to males and doctors. Medical staff in the general ward considered the severity of the COVID-19 pandemic situation higher. Nurses perceived work changes (p < 0.05), work burden (p < 0.05), and personal impact (p < 0.05) more serious than doctors. Medical staff in Level 3 emergency department (ED) perceived a lack of real-time information (p = 0.012), a lack of resources, and negative personal impacts associated with the pandemic as more serious than staff in Level 1 and Level 2 EDs. Medical staff in the intensive care unit perceived work changes (p < 0.05), work burden (p < 0.05), and lack of personal protective equipment (p = 0.002) as more serious than staff in the ED and general ward. Conclusion: Providing real-time information and resources for reducing work burden and negative personal impact is central to maximizing the work output of the COVID-19 pandemic frontline medical staff. Supporting their mental health through regular programs and intervention is also imperative.

Impact of the COVID-19 Pandemic on Emergency Department Workload and Emergency Care Workers' Psychosocial Stress in the Outbreak Area.

Background and Objectives: Due to the unexpected spread of coronavirus disease 2019 (COVID-19), there was a serious crisis of emergency medical system collapse. Healthcare workers working in the emergency department were faced with psychosocial stress and workload changes. Materials and Methods: This was a cross-sectional survey of healthcare workers in the emergency department in Daegu and Gyeongbuk, Korea, from November 16 to 25, 2020. In the survey, we assessed the general characteristics of the respondents; changes in the working conditions before and after the COVID-19 pandemic; and resulting post-traumatic stress disorder, depression and anxiety statuses using 49 questions. Results: A total of 529 responses were collected, and 520 responses were included for the final analyses. Changes in working conditions and other factors due to COVID-19 varied by emergency department level, region and disease group. Working hours, intensity, role changes, depression and anxiety scores were higher in the higher level emergency department. Isolation ward insufficiency and the risk of infection felt by healthcare workers tended to increase in the lower level emergency department. Treatment and transfer delay were higher in the fever and respiratory disease groups (M = 3.58, SD = 1.18; M = 4.08, SD = 0.95), respectively. In all the disease groups, both treatment and transfer were delayed more in Gyeongbuk than in Daegu. Conclusions: Different goals should be pursued by the levels and region of the emergency department to overcome the effects of the COVID-19 pandemic and promote optimal care.

Relations of Augmented Systolic Annular Expansion and Leaflet/Papillary Muscle Dynamics in Late-Systolic Mitral Valve Prolapse Evaluated by Echocardiography with a Speckle Tracking Analysis.

The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets.MV annulus systolic expansion, PMs' systolic superior shift, and MV leaflets' systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP.PMs' superior shift, MV leaflets' lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets' lengthening and PMs' superior shift as independent factors associated with MV annular expansion.Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets' lengthening and PMs' superior shift.

Obstruction of the Hepatic Venous Flow Caused by Intravenous Leiomyomatosis.

Budd-Chiari syndrome (BCS) is a rare intrahepatic vascular disease that is characterized by a hepatic venous outflow obstruction. Intravenous leiomyomatosis (ILs) is a rare complication of a myoma. Here, we report a case of BCS that was caused by intracaval ILs. A woman presented to the emergency department (ED) with abdominal distension that had gradually progressed over a period of 3 years. Bedside ultrasonography and contrast-enhanced computed tomography (CECT) showed a large ascites and pelvic mass. The mass continued to the inferior vena cava and the right atrium. The intracaval mass was obstructing the left and middle hepatic veins. We established a tentative diagnosis of BCS caused by intracaval ILs and attempted surgical resection. Complete resection of the intracaval mass failed because of adhesion; however, she was discharged from the hospital without any postoperative complications. After 3 months, a pelvic ultrasonography showed a recurrence of a 4 × 3 cm pelvic mass. The mass size increased to 6 cm after 30 months. ILs can cause secondary BCS and can lead to life-threatening conditions. Owing to its extreme rarity, early detection in the ED is challenging. Bedside ultrasonography and CECT can enable the early recognition of BCS by ILs.

Possible mechanism of late systolic mitral valve prolapse: systolic superior shift of leaflets secondary to annular dilatation that causes papillary muscle traction.

Progressive superior shift of the mitral valve (MV) during systole is associated with abnormal papillary muscle (PM) superior shift in late systolic MV prolapse (MVP). The causal relation of these superior shifts remains unclarified. We hypothesized that the MV superior shift is related to augmented MV superiorly pushing force by systolic left ventricular pressure due to MV annular dilatation, which can be corrected by surgical MV plasty, leading to postoperative disappearance of these superior shifts. In 35 controls, 28 patients with holosystolic MVP, and 28 patients with late systolic MVP, the MV coaptation depth from the MV annulus was measured at early and late systole by two-dimensional echocardiography. The PM tip superior shift was monitored by echocardiographic speckle tracking. MV superiorly pushing force was obtained as MV annular area × (systolic blood pressure - 10). Measurements were repeated after MV plasty in 14 patients with late systolic MVP. Compared with controls and patients with holosystolic MVP, MV and PM superior shifts and MV superiorly pushing force were greater in patients with late systolic MVP [1.3 (0.5) vs. 0.9 (0.6) vs. 3.9 (1.0) mm/m2, 1.3 (0.5) vs. 1.2 (1.0) vs. 3.3 (1.3) mm/m2, and 487 (90) vs. 606 (167) vs. 742 (177) mmHg·cm2·m-2, respectively, means (SD), P < 0.001]. MV superior shift was correlated with PM superior shift ( P < 0.001), which was further related to augmented MV superiorly pushing force ( P < 0.001). MV and PM superior shift disappeared after surgical MV plasty for late systolic MVP. These data suggest that MV annulus dilatation augmenting MV superiorly pushing force may promote secondary superior shift of the MV (equal to late systolic MVP) that causes subvalvular PM traction in patients with late systolic MVP. NEW & NOTEWORTHY Late systolic mitral valve prolapse (MVP) is associated with mitral valve (MV) and papillary muscle (PM) abnormal superior shifts during systole, but the causal relation remains unclarified. MV and PM superior shifts were correlated with augmented MV superiorly pushing force by annular dilatation and disappeared after surgical MV plasty with annulus size and MV superiorly pushing force reduction. This suggests that MV annulus dilatation may promote secondary superior shifts of the MV (late systolic MVP) that cause subvalvular PM traction.

Effects of laser-assisted thinning versus opening on clinical outcomes according to maternal age in patients with repeated implantation failure.

Laser-assisted thinning (LAT) and laser-assisted opening (LAO) are performed as part of human in vitro fertilization (IVF) to increase the implantation rate in patients with a poor prognosis and in cases of repeated implantation failure. However, an insufficient number of studies have directly compared LAT and LAO using the same methods. Therefore, we compared the effects of LAT and LAO on clinical outcomes according to maternal age in patients with repeated implantation failure. This retrospective study was performed in 509 IVF cycles (458 patients). The cycles were divided based on maternal age and the method used (< 38 years LAT, n = 119 vs. LAO, n = 179 and ≥ 38 years LAT, n = 72 vs. LAO, n = 139). Cleavage-stage embryos before transfer were either thinned or opened using a 1.46-µm noncontact diode laser. We compared the implantation rates and pregnancy outcomes of cycles between LAT and LAO according to maternal age. The characteristics of patients did not differ significantly among the groups (p > 0.05), with the exception of mixed factor infertility, which was more common in the LAT group than in the LAO group among patients < 38 years of age (10.1% vs. 2.8%, p = 0.008). The LAT and LAO groups showed similar rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, abortion, implantation, singleton pregnancy, and twin pregnancy (p > 0.05). In conclusion, LAT and LAO had similar clinical outcomes. Therefore, we did not find any evidence that LAT is superior to LAO. In fact, the patients ≥ 38 years of age who underwent LAO tended to have a lower abortion rate. Further study is necessary to confirm these results in a larger population.

Characterization of 4 TaGAST genes during spike development and seed germination and their response to exogenous phytohormones in common wheat.

Gibberellic acid (GA) is involved in the regulation of plant growth and development. We defined GA-stimulated transcript (GAST) gene family and characterized its four members (TaGAST1, 2, 3, and 4) in wheat spikes. Triticum aestivum whole spikes were collected at ten developmental stages and dehulled spikelets were obtained at various days after flowering. Expression of TaGAST1, 2, 3, and 4 was analyzed using RT-PCR at inflorescence development stages, in different tissues, and after phytohormones application. To identify proteins interacting with TaGAST1, yeast two-hybridization was performed and BiFC analysis was used for verification. TaGAST1 was expressed at the inflorescence stage and only expressed in seedlings under abscisic acid (ABA) treatment after phytohormone treatment. TaGAST2 and TaGAST3 showed moderate expression in the spike, vigorous transcript accumulation in the seedling, and up-regulation by exogenous GA in early germination stages. TaGAST4 was predominantly expressed in the seedling. Wheat cyclophilin A-1 (TaCypA1), identified as a TaGAST1-interacting protein, showed opposite expression pattern in the developing spike to TaGAST1. TaCypA1 transcript was slightly up-regulated by GA, slightly down-regulated by paclobutrazol, and was maintained after ABA treatment. The interaction of TaGAST1 with TaCypA1 is targeted to the plasma membrane. TaGAST1 was specifically expressed in the wheat spike and was stimulated by exogenous GA treatment. TaGAST2 and TaGAST3 expression in germinating seeds and seedlings was higher than that in the spike stage. TaGAST4 was not expressed in all developmental stages. TaGAST1 and TaCypA1 might be expressed antagonistically during wheat spike development.

3,4,5-tricaffeoylquinic acid attenuates proteasome inhibition-mediated programmed cell death in differentiated PC12 cells.

The dysfunction of the proteasome system is suggested to be implicated in neuronal degeneration. Caffeoylquinic acid derivatives have demonstrated anti-oxidant and anti-inflammatory effects. However, the effect of 3,4,5-tricaffeoylquinic acid on the neuronal cell death induced by proteasome inhibition has not been studied. Therefore, in the respect of cell death process, we assessed the effect of 3,4,5-tricaffeoylquinic acid on the proteasome inhibition-induced programmed cell death using differentiated PC12 cells. The proteasome inhibitors MG132 and MG115 induced a decrease in Bid, Bcl-2, and survivin protein levels, an increase in Bax, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), and an increase in the tumor suppressor p53 levels. Treatment with 3,4,5-tricaffeoylquinic acid attenuated the proteasome inhibitor-induced changes in the programmed cell death-related protein levels, formation of reactive oxygen species, GSH depletion and cell death. The results show that 3,4,5-tricaffeoylquinic acid may attenuate the proteasome inhibitor-induced programmed cell death in PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect of 3,4,5-tricaffeoylquinic acid appears to be attributed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.

Enhancing genome editing in hPSCs through dual inhibition of DNA damage response and repair pathways.

Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

Mechanisms underlying the changes in the structural, physicochemical, and emulsification properties of porcine myofibrillar proteins induced by prolonged pulsed electric field treatment.

This study aimed to explore how pulsed electric field (PEF) treatment affects the structural, physicochemical, and emulsification properties of porcine-derived myofibrillar proteins (MPs). Increasing PEF treatment induced partial polarization and protein unfolding, resulting in notable denaturation that affected both the secondary and tertiary structures. PEF treatment also improved the solubility and emulsification ability of MPs by reducing their pH and surface hydrophobicity. Confocal laser scanning microscopy confirmed the effective adsorption of MPs and PEF-treated MPs at the oil/water interface, resulting in well-fabricated Pickering emulsions. A weak particle network increased the apparent viscosity in short-term PEF-treated Pickering emulsions. Conversely, in emulsions with long-term PEF-treated MP, rheological variables decreased, and dispersion stability increased. These results endorse the potential application of PEF-treated porcine-derived MPs as efficient Pickering stabilizers, offering valuable insights into the creative use of PEF for enhancing high-quality meat products, meeting the increasing demand for clean-label choices.

Effects of myofibril-palatinose conjugate as a phosphate substitute on meat emulsion quality.

The objective of this study was to investigate a replacement for phosphate in meat products. Protein structural modification was employed in this study, and grafted myofibrillar protein (MP) with palatinose was added to meat emulsion without phosphate. Here, 0.15% of sodium polyphosphate (SPP) was replaced by the same (0.15%) concentration and double (0.3%) the concentration of grafted MP. Although the thermal stability was decreased, the addition of transglutaminase could increase stability. The rheological properties and pH also increased with the addition of grafted MP and transglutaminase. The addition of grafted protein could be perceived by the naked eye by observing a color difference before cooking, but it was not easy to detect after cooking. The cooking loss, emulsion stability, water holding capacity, lipid oxidation, and textural properties improved with the addition of grafted MP. However, the excessive addition of grafted MP and transglutaminase was not recommended to produce a high quality of phosphate replaced meat emulsion, and 0.15% was identified as a suitable addition ratio of grafted MP.

Remodeling of sorafenib as an orally bioavailable ferroptosis inducer for Lung Cancer by chemical modification of adenine-binding motif.

Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc- (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics.

Fabrication of a silica nanocable using hydroxyl-group core-engineered filamentous virus.

Biological materials with surface-active proteins can be genetically modified to bind target materials. In particular, filamentous-shaped M13 bacteriophages (M13 phage) are attractive scaffolds for functional nanostructures due to their highly ordered protein-coat surface. This paper demonstrates a simple method for fabricating silica nanocables along a modified M13 phage. The M13 phage was genetically engineered to display the amino acid serine on the surface to provide hydroxyl groups for a sol-gel reaction. This M13 phage mutant offers homogeneous molecular templates for forming silica coated coaxial nanocables. Silica shell formation was confirmed by transmission electron microscopy (TEM) and electron dispersive X-ray (EDX) analysis. The core-shell structures were clearly distinguishable in the TEM analysis, and the synthesized shells were observed by EDX analysis. In addition, we investigated the adsorption properties of M13 phages on the pretreated substrate as a function of concentration. The effect of the relative concentration of M13 phages on the substrate was observed by using atomic force microscopy (AFM). We also fabricated top electrodes on the extremely dense network for measuring electrical properties of the M13 phage. The experimental DC measurement indicated that the wild-type phage has very low electrical conductance, similar to insulating material.