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Micronuclei are small DNA-containing nuclear structures that are spatially isolated from the main nucleus. They are frequently found in pathologies, including cancer. It was recently shown that these nuclear structures are not only biomarkers of disease but also play an active role in tumor biology. Many consequences of micronucleus formation on tumor biology are dependent on the frequent and irreversible rupture of their nuclear envelopes, which results in the exposure of their DNA contents to the cytoplasm. In this review, we discuss models of defective nuclear envelope deposition on missegregated chromosomes that lead to nuclear envelope rupture. Furthermore, we expound upon the various downstream consequences of micronucleus nuclear envelope rupture on cells. These consequences include a massive DNA rearrangement phenomenon called chromothripsis and activation of the cGAS-STING innate immune signaling pathway, which can be a double-edged sword with tumorigenesis and tumor prevention functions. Although micronuclei are small structures, the impact they have on cells and their microenvironment is quite large.Cancer: Rupture of micronuclei drives genome instabilityMicronuclei, which contain faulty chromosomes or chromosome fragments and occur outside the main cellular nucleus, are prone to rupturing, which leads to DNA changes that can drive tumor development. A team led by Mijung Kwon from Ewha Womans University in Seoul and Jae-Ho Lee of Ajou University School of Medicine in Suwon, both in South Korea, review how these micronuclei tend to burst, spilling their contents into the cell with devastating consequences. The chromosomes they contain break into tiny fragments and this broken DNA finds its way into the main nucleus, leading to chromosomal rearrangements that can permanently alter genomic function. The rupture of micronuclei also activates a part of the innate immune system that can promote cancer cell invasion and spread. Drugs targeting these processes could aid in the treatment of cancer.

To evaluate the changes of vaginal microbiota during cervical carcinogenesis in women with high-risk human papillomavirus infection. Vaginal microbiota was analyzed using next-generation sequencing in women with normal, cervical intraepithelial neoplasia (CIN), or cervical cancer. A marked decrease of Lactobacillus crispatus was found in the CIN/cancer groups compared with that in the normal group. The diversity of microorganisms increased in patients with CIN or cervical cancer with HPV infection. Atopobium vaginae (OR 4.33, 95% CI 1.15-16.32), Dialister invisus (OR 4.89, 95% CI 1.20-19.94), Finegoldia magna (OR 6.00, 95% CI 1.08-33.27), Gardnerella vaginalis (OR 7.43, 95% CI 1.78-31.04), Prevotella buccalis (OR 11.00, 95% CI 2.00-60.57), and Prevotella timonensis (OR 6.00, 95% CI 1.46-24.69) were significantly associated with the risk of CIN 2/3 or cervical cancer. Women with the CIN and cervical cancer showed a high diversity in vaginal microbiota. Depletion of Lactobacillus crispatus and increased abundance of anaerobic bacteria were detected in women with cervical disease.

Sterol regulatory element binding protein (SREBP) cleavage activating protein (SCAP) is a key regulator of SREBP maturation. SCAP induces translocation of SREBP from the endoplasmic reticulum to the Golgi apparatus, allowing it to regulate cellular triglyceride and cholesterol levels. Previous studies have shown that suppression of SREBP activation in SCAP conditional knockout mice reduced the accumulation of intracellular triglycerides, which eventually causes the development of metabolic diseases such as atherosclerosis, diabetes, hepatic steatosis, and insulin resistance. However, despite the significance of SCAP as a regulator of SREBP, its function has not been thoroughly discussed. In this review, we have summarized the function of SCAP and its regulatory proteins. Furthermore, we discuss recent studies regarding SCAP as a possible therapeutic target for hypertriglyceridemia and hyperlipidemia.Metabolic diseases: blocking fat and cholesterol productionThe complex cellular functions of a membrane protein that influences fat and cholesterol levels have been reviewed by researchers in South Korea. The main role of this protein, SCAP, is to move certain transcription factors between organelles within cells, allowing them to regulate the synthesis of triglycerides (fat molecules) and cholesterol. Seung-Soon Im and co-workers at Keimyung University School of Medicine in Daegu reviewed studies of the numerous signalling pathways that influence SCAP activity, and of insulin-induced genes that bind to SCAP and inhibit its function. Genetic studies have shown that blocking SCAP in mice can reduce the development of diabetes, fatty liver disease and atherosclerosis. Several drugs for these metabolic conditions have been shown to indirectly inhibit SCAP activity, and therefore drugs that directly target SCAP should be a focus of future research.

Although depression and anxiety represent significant yet treatable comorbidities in patients with idiopathic pulmonary fibrosis (IPF), their impact on the clinical course and prognosis of IPF remain unclear. We investigated the prevalence and clinical significance of depression and anxiety in patients with IPF. The present study included a prospective cohort comprising 112 Korean patients with IPF who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. Symptoms of depression and anxiety were present in 25.9% and 21.4% of patients with IPF, respectively (HADS scores ≥8). No significant differences in demographic data, age, sex, smoking status, Modified Medical Research Council Dyspnea Scale (MMRC) scores, pulmonary function tests, or Gender-Age-Physiology Index for IPF were observed between patients with depression or anxiety and those without. However, in patients with anxiety, St. George's Respiratory Questionnaire (SGRQ) scores were significantly higher than those of patients without anxiety (40.5 versus 23.5; p = 0.003). The survival rate and total number of hospital admissions did not significantly differ between patients with depression/anxiety and those without. Our findings indicate that depression and anxiety are relatively common in patients with IPF. Although no significant differences were noted with regard to survival rate and hospitalization, the present study suggests that depression and anxiety significantly influence quality of life in patients with IPF.

There are many perspectives on the advantages of introducing blockchain in the medical field, but there are no published feasibility studies regarding the storage, propagation, and management of personal health records (PHRs) using blockchain technology. The purpose of this study was to investigate the usefulness of blockchains in the medical field in relation to transactions with and propagation of PHRs in a private blockchain. We constructed a private blockchain network using Ethereum version 1.8.4 and conducted verification using the de-identified PHRs of 300 patients. The private blockchain network consisted of one hospital node and 300 patient nodes. In order to verify the effectiveness of blockchain-based PHR management, PHRs at a time were loaded in a transaction between the hospital and patient nodes and propagated to the whole network. We obtained and analyzed the time and gas required for data transaction and propagation on the blockchain network. For reproducibility, these processes were repeated 100 times. Of 300 patient records, 74 (24.7%) were not loaded in the private blockchain due to the data block size of the transaction block. The remaining 226 individual health records were classified into groups A (80 patients with outpatient visit data less than 1 year old), B (84 patients with outpatient data from between 1 and 3 years before data collection), and C (62 patients with outpatient data 3 to 5 years old). With respect to mean transaction time in the blockchain, C (128.7 seconds) had the shortest time, followed by A (132.2 seconds) and then B (159.0 seconds). The mean propagation times for groups A, B, and C were 1494.2 seconds, 2138.9 seconds, and 4111.4 seconds, respectively; mean file sizes were 5.6 KB, 18.6 KB, and 45.38 KB, respectively. The mean gas consumption values were 1,900,767; 4,224,341; and 4,112,784 for groups A, B, and C, respectively. This study confirms that it is possible to exchange PHR data in a private blockchain network. However, to develop a blockchain-based PHR platform that can be used in practice, many improvements are required, including reductions in data size, improved personal information protection, and reduced operating costs.

Chromosomal instability (CIN) in cancer cells has been reported to activate the cGAS–STING innate immunity pathway via micronuclei formation, thus affecting tumor immunity and tumor progression. However, adverse effects of the cGAS/STING pathway as they relate to CIN have not yet been investigated. We addressed this issue using knockdown and add-back approaches to analyze each component of the cGAS/STING/TBK1/IRF3 pathway, and we monitored the extent of CIN by measuring micronuclei formation after release from nocodazole-induced mitotic arrest. Interestingly, knockdown of cGAS (cyclic GMP-AMP synthase) along with induction of mitotic arrest in HeLa and U2OS cancer cells clearly resulted in increased micronuclei formation and chromosome missegregation. Knockdown of STING (stimulator of interferon genes), TBK1 (TANK-binding kinase-1), or IRF3 (interferon regulatory factor-3) also resulted in increased micronuclei formation. Moreover, transfection with cGAMP, the product of cGAS enzymatic activity, as well as add-back of cGAS WT (but not catalytic-dead mutant cGAS), or WT or constitutively active STING (but not an inactive STING mutant) rescued the micronuclei phenotype, demonstrating that all components of the cGAS/STING/TBK1/IRF3 pathway play a role in preventing CIN. Moreover, p21 levels were decreased in cGAS-, STING-, TBK1-, and IRF3-knockdown cells, which was accompanied by the precocious G2/M transition of cells and the enhanced micronuclei phenotype. Overexpression of p21 or inhibition of CDK1 in cGAS-depleted cells reduced micronuclei formation and abrogated the precocious G2/M transition, indicating that the decrease in p21 and the subsequent precocious G2/M transition is the main mechanism underlying the induction of CIN through disruption of cGAS/STING signaling.Cancer: Keeping chromosomes stable during cell divisionSignaling through cGAS, a protein that detects DNA in the cytosol, prevents chromosome instability (CIN) in cancer cells by regulating the levels of the cell-cycle inhibitor p21. Alterations in chromosome number or structure are hallmarks of cancer cells, but their contribution to disease is unclear. Previous studies have shown that CIN activates cGAS, triggering the activation of an immune response and cell death. However, Jae-Ho Lee at Ajou University, Suwon, South Korea and colleagues now show that defects in cGAS signaling in cells treated with a drug that stops cell-cycle progression leads to CIN and the formation of extra-nuclear bodies containing damaged chromosome fragments, known as micronuclei. Restoring cGAS activity or increasing p21 expression levels prevented micronuclei formation, highlighting a mechanism through which cancer cells can maintain chromosomal stability.

Alcohol-induced fatty liver disease is a significant contributor to global mortality, primarily resulting from excessive alcohol consumption and subsequent hepatic damage. This study investigated the therapeutic potential of MF001, an aldehyde-reducing compound derived from the yeast Saccharomyces cerevisiae in alcohol-induced liver damage. Using a Lieber-DeCarli ethanol diet-induced live disease model, we assessed the effects of MF001 on lipogenesis, oxidative stress, and inflammation. MF001 treatment significantly reduced lipid accumulation, as indicated by decreased expression of lipogenic genes. Moreover, MF001 suppresses reactive oxygen species (ROS) production indicated by reduced malondialdehyde levels and ROS-associated inflammatory markers, including Tnf-α, Il-6, and Mcp-1. Histological analysis revealed decreased hepatic lipid deposition and inflammation following MF001 administration. Furthermore, MF001 modulated alcohol metabolism by downregulating Cyp2e1 and Adh1, thereby decreasing acetaldehyde accumulation and improving liver function, as evidenced by normalized ALT and AST levels. Our findings suggest that MF001 alleviates alcohol-induced liver damage through its anti-inflammatory, antioxidant, and lipid-lowering properties, highlighting its potential as a function agent for preventing and treating alcohol-induced fatty liver disease.

Background South Korea experiences the highest diabetes-related hospitalization rates among OECD countries. Although integrated primary care could potentially lower preventable hospitalizations and healthcare costs, the limited uptake of a usual source of care (USC) and underdeveloped primary care services in Korea have impeded progress, and the role and functions of primary care remain insufficiently defined. Methods This study investigated how having a USC affects medical expenditures in adults with diabetes by using Korea Health Panel data from 2019 to 2022, spanning the pre-pandemic (2019) and pandemic (2020–2022) periods. The analysis included 6,144 individuals. The main independent variable was the type and quality of USC, categorized into three groups: no USC, place-only USC, and physician-based USC. Quality was assessed by patient-reported comprehensiveness and coordination, combined into an integrated quality index. We applied panel regression analysis using the Hausman–Taylor estimation technique to address both time-varying and time-invariant covariates while mitigating endogeneity concerns. Results Between 2019 and 2022, the proportion of individuals with a physician at a regular location serving as their USC increased from 58.5% to 66.1%, while the proportion without a physician as their USC decreased from 15.1% to 10.9%, with larger variation among vulnerable populations. The physician-based USC group consistently incurred higher absolute expenditures but showed the smallest relative increase during the pandemic, compared with sharp rises in the no-USC and place-only USC groups. Adults with diabetes whose USC was a high-quality primary care physician—defined by favorable patient ratings of comprehensiveness and coordination—were associated with approximately 13.1% lower healthcare expenditures compared to those lacking a physician as their USC ( β = − 0.140, P  = 0.006). Moreover, community clinic–based physicians as USC were associated with lower expenditures, while hospital-based USC was associated with higher costs, though not statistically significant. Conclusion These findings underscore the importance of increasing access to high-quality primary care physicians as USC to optimize chronic disease management and maintain sustainable healthcare systems.

According to estimates by GLOBOCAN 2012, the incidence of this cancer (age standardised rate 58·3% per 100 000 population) is more than 15 times greater than that of the UK and 5·6 times that of the USA.2 The proportion of small (<1 cm) tumours detected increased from 6·1% in 1962, to 43·1% in 2009; however, mortality rates have been almost constant during the past three decades.3 Without any particular natural or man-made disasters, such as nuclear accidents, causes of this increase in thyroid cancer are difficult to account for, except because of possible overdiagnosis of slow or nonprogressing tumours;4 a result of a medical system that encourages cancer screening.5 The Korean National Cancer Center and many university affiliated hospitals recommend ultrasonography to screen asymptomatic people for thyroid cancer.6 With increases in the number of people diagnosed with thyroid cancer, the general public and doctors both feel under pressure to detect very small-sized thyroid tumours as early as possible, leading to high numbers of diagnoses for thyroid cancer.

Kiwifruit ( Actinidia deliciosa )-derived actinidin, a cysteine protease, is renowned for its meat-tenderizing and milk-clotting activities. Despite its potential in various biotechnological applications, an efficient expression platform for actinidin production has not yet been developed. Instead, actinidin has traditionally been purified directly from the fruits of various plants. This study aimed to produce kiwifruit-derived actinidin in the leaves of Nicotiana benthamiana . The expressed actinidin was directed to the lumen of the endoplasmic reticulum (ER) using the binding immunoglobulin protein (BiP) signal sequence and an ER retention signal. To facilitate cost-effective purification, the family 3 cellulose-binding module (CBM3) was employed as an affinity tag, along with microcrystalline cellulose beads that bind efficiently to CBM3. A significant portion of the expressed actinidin was recovered in the soluble fraction without proteolytic degradation. The purified actinidin exhibited β-casein-degrading activity, with optimal efficiency observed at 55°C and pH 7.0. These results establish a promising plant-based platform for the efficient production and functional application of kiwifruit-derived actinidin in diverse biotechnological processes.