Purpose: While TP53 mutations are well known to be associated with adverse prognosis in hematological diseases, their functional impact remains incompletely understood. This study examines the spectrum of TP53 mutations across various hematologic malignancies and evaluates their functional impact. Materials and Methods: Using targeted sequencing panels, we analyzed TP53 mutations in the bone marrow aspiration samples of a retrospective cohort of 856 patients diagnosed with hematologic malignancies. To assess the impact of TP53 mutations, we applied the evolutionary action (EAp53) score and the relative fitness score (RFS), previously proposed functional scoring methods. The effects of variant allele frequency (VAF), disruptive mutations, EAp53 score, and RFS on overall survival (OS) were evaluated. Results: TP53 mutations were associated with inferior OS compared with wildtype TP53 (median OS 10.0 months versus not estimable; hazard ratio (HR) 4.6; p<0.001). In the acute myeloid leukemia, multiple myeloma, and myelodysplastic syndrome subgroups, TP53 mutations had a significant adverse impact on OS. (HRs 3.8, 4.2, 6.0, respectively; p<0.001, p=0.005, p<0.001, respectively). Patients with VAF >50% had significantly poorer OS compared to those with VAF ≤50% (median OS 7.5 months versus 22.8 months; HR 2.2, p=0.016). Moreover, patients in the high-risk RFS group (RFS >0.22) had significantly worse OS compared to those in the low-risk RFS group (RFS ≤0.22) (median OS 5.6 months versus 16.3 months; HR 2.2, p=0.041). However, no significant survival difference was observed between the EAp53 high-risk (>75) and low-risk (≤75) groups, or between patients with disruptive and non-disruptive mutations. Conclusion Our findings highlight VAF and RFS as valuable tools for stratifying TP53-mutant patients into high-risk and low-risk groups.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal-dominant neurodegenerative disorder caused by an expanded polyglutamine repeat in the ataxin-3 gene. The resulting mutant ataxin-3 protein forms intraneuronal inclusions that lead to neurodegeneration in the cerebellum and other brain regions. This study aimed to develop a novel nonhuman primate model of SCA3 to address the limitations of existing knock-in and transgenic models using an adeno-associated virus (AAV) to deliver the mutant gene. AAV viral vectors carrying mutant ataxin-3 were stereotaxically injected into the cerebellum of monkeys. The animals were monitored over an 8-week period, during which behavioral and neuroimaging assessments were conducted. This was followed by a detailed pathological examination. The AAV vector successfully spread throughout the cerebellum, and the expression of mutant ataxin-3 was confirmed. Neuroimaging revealed a reduction in N-acetylaspartate (NAA) levels, whereas histological analysis showed significant damage to the Purkinje cell layer. Notably, the monkeys exhibited sleep disturbances, a prodromal symptom commonly observed in human patients with SCA3. AAV-mediated delivery of mutant ataxin-3 can effectively replicate the key pathological and clinical features of SCA3 in primates. This approach offers a promising new model for studying disease mechanisms and evaluating potential therapies.

Purpose: We investigated the ophthalmic manifestations observed in patients diagnosed with ocular myasthenia gravis. Methods: In total, 58 patients diagnosed with ocular myasthenia gravis visited the ophthalmology and neurology departments between January 2011 and August 2022. Patients were followed for > 6 months; their ophthalmic manifestations were analyzed retrospectively. Results: The study included 29 males and 29 females with a mean age of 55.52 ± 15.60 years. Among the patients, 31 tested positive for anti-acetylcholine receptor antibodies, resulting in a positive rate of 53.45%. Abnormalities in repeated nerve stimulation tests were observed in 33.33% of the patients. The antibody-positive group exhibited a higher frequency of progression to generalized myasthenia gravis (p = 0.011) and a higher incidence of chest abnormalities (p < 0.001) compared to the antibody-negative group. Horizontal and vertical diplopia were commonly observed in a complex group of patients with diplopia and blepharoptosis (p < 0.001); there was a difference in the pattern of strabismus between the diplopia single group with esotropia and the complex group with exotropia (p = 0.029). In addition, the combination group demonstrated a higher antibody titer (p = 0.034), a higher frequency of abnormalities in repeated nerve stimulation tests (p = 0.022), and a higher incidence of chest abnormalities (p = 0.022). Conclusions The anti-acetylcholine receptor antibody-positive group had a higher incidence of progression to generalized myasthenia gravis; moreover, the complex group of patients with diplopia and ptosis exhibited elevated levels of anti-acetylcholine receptor antibodies and frequently accompanied both horizontal and vertical strabismus.

Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality. Twin pregnancy and cesarean delivery are well-known risk factors for PPH. However, few studies have investigated PPH risk factors in mothers who have undergone cesarean delivery for twin pregnancies. Therefore, this study investigated the risk factors associated with severe PPH after cesarean delivery for twin pregnancies. Methods: We searched and reviewed the Korean Health Insurance Review and Assessment Service’s claims data from July 2008 to June 2021 using the code corresponding to cesarean delivery for twin pregnancy. Severe PPH was defined as hemorrhage requiring red blood cell (RBC) transfusion during the peripartum period. The risk factors associated with severe PPH were identified among the procedure and diagnosis code variables and analyzed using univariate and multivariate logistic regressions. Results: We analyzed 31,074 cesarean deliveries for twin pregnancies, and 4,892 patients who underwent cesarean deliveries for twin pregnancies and received RBC transfusions for severe PPH were included. According to the multivariate analysis, placental disorders (odds ratio, 4.50; 95% confidence interval, 4.09– 4.95; P < 0.001), general anesthesia (2.33, 2.18–2.49; P < 0.001), preeclampsia (2.20, 1.99–2.43; P < 0.001), hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (2.12, 1.22–3.68; P = 0.008), induction failure (1.37, 1.07–1.76; P = 0.014), and hypertension (1.31, 1.18–1.44; P < 0.001) predicted severe PPH. Conclusions: Placental disorders, hypertensive disorders such as preeclampsia and HELLP syndrome, and induction failure increased the risk of severe PPH after cesarean delivery for twin pregnancy

Cadmium (Cd) exposure primarily occurs through inhalation, either by smoking or occupational exposure to contaminated air. Upon inhalation, Cd ultimately reaches the prostate through the bloodstream. In this review, we investigate the carcinogenic potential of Cd in both respiratory organs and the prostate. Specifically, this review examines cellular metabolism, comprehensive toxicity, and carcinogenic mechanisms by exploring gene ontology, biological networks, and adverse outcome pathways. In the respiratory organs, Cd induces lung cancer by altering the expression of IL1B and FGF2, causing DNA damage, reducing cell junction integrity, and promoting apoptosis. In the prostate, Cd induces prostate cancer by modifying the expression of EDN1 and HMOX1, leading to abnormal protein activities and maturation, suppressing tumor suppressors, and inducing apoptosis. Collectively, this review provides a comprehensive understanding of the carcinogenic mechanisms of Cd in two different organs by adopting toxicogenomic approaches. These insights can serve as a foundation for further research on cadmium-induced cancer, contributing to the establishment of future cancer prevention strategies.