Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.

Loss of SREBP-1c ameliorates iron-induced liver fibrosis by decreasing lipocalin-2.

Sterol regulatory element-binding protein (SREBP)-1c is involved in cellular lipid homeostasis and cholesterol biosynthesis and is highly increased in nonalcoholic steatohepatitis (NASH). However, the molecular mechanism by which SREBP-1c regulates hepatic stellate cells (HSCs) activation in NASH animal models and patients have not been fully elucidated. In this study, we examined the role of SREBP-1c in NASH and the regulation of LCN2 gene expression. Wild-type and SREBP-1c knockout (1cKO) mice were fed a high-fat/high-sucrose diet, treated with carbon tetrachloride (CCl4), and subjected to lipocalin-2 (LCN2) overexpression. The role of LCN2 in NASH progression was assessed using mouse primary hepatocytes, Kupffer cells, and HSCs. LCN2 expression was examined in samples from normal patients and those with NASH. LCN2 gene expression and secretion increased in CCl4-induced liver fibrosis mice model, and SREBP-1c regulated LCN2 gene transcription. Moreover, treatment with holo-LCN2 stimulated intracellular iron accumulation and fibrosis-related gene expression in mouse primary HSCs, but these effects were not observed in 1cKO HSCs, indicating that SREBP-1c-induced LCN2 expression and secretion could stimulate HSCs activation through iron accumulation. Furthermore, LCN2 expression was strongly correlated with inflammation and fibrosis in patients with NASH. Our findings indicate that SREBP-1c regulates Lcn2 gene expression, contributing to diet-induced NASH. Reduced Lcn2 expression in 1cKO mice protects against NASH development. Therefore, the activation of Lcn2 by SREBP-1c establishes a new connection between iron and lipid metabolism, affecting inflammation and HSCs activation. These findings may lead to new therapeutic strategies for NASH.

Phloroglucinol Enhances Anagen Signaling and Alleviates H2O2-Induced Oxidative Stress in Human Dermal Papilla Cells.

Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of ß-Catenin. Since several anagen-inductive genes are regulated by ß-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated ß-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3ß/ß-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H2O2)-induced HDPCs. The senescence-associated ß-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H2O2-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.

Comparison of the Usefulness of Computer-Assisted Three-Dimensional Analysis and Weight-Bearing Radiographs in Ankle Osteoarthritis.

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.

Therapeutic effects of a novel electrode for transcranial direct current stimulation in ischemic stroke mice.

Rationale: Non-invasive transcranial direct current stimulation (tDCS), a promising stimulation tool to modulate a wide range of brain disorders, has major limitations, such as poor cortical stimulation intensity and focality. We designed a novel electrode for tDCS by conjugating a needle to a conventional ring-based high-definition (HD) electrode to enhance cortical stimulation efficacy. Method: HD-tDCS (43 µA/mm2, charge density 51.6 kC/m2, 20 min) was administered to male C57BL/6J mice subjected to early-stage ischemic stroke. Behavioral tests were employed to determine the therapeutic effects, and the underlying mechanisms of HD-tDCS were determined by performing RNA sequencing and other biomedical analyses. Results: The new HD-tDCS application, showing a higher electric potential and spatial focality based on computational modeling, demonstrated better therapeutic effects than conventional HD-tDCS in alleviating motor and cognitive deficits, with a decrease in infarct volume and inflammatory response. We assessed different electrode configurations in the new HD electrode; the configurations variously showed potent therapeutic effects, ameliorating neuronal death in the peri-infarct region via N-methyl-D-aspartate-dependent sterol regulatory element-binding protein 1 signaling and related inflammatory factors, further alleviating motor and cognitive deficits in stroke. Conclusion: This new HD-tDCS application showed better therapeutic effects than those with conventional HD-tDCS in early-stage stroke via the amelioration of neuronal death in the penumbra. It may be applied in the early stages of stroke to alleviate neurological impairment.

Is prophylactic intraoperative transfusion needed in unilateral total knee arthroplasty? Comparison of hematologic data and postoperative transfusion rate between a prophylactic allogenic or autologous transfusion group with a no-transfusion group: A preliminary retrospective cohort study.

OBJECTIVES: To determine whether prophylactic intra-operative allogenic or autologous transfusion could prevent postoperative anemia and additional transfusion comparing to the control group without receiving any prophylactic intervention in unilateral total knee arthroplasty. MATERIALS AND METHODS: This study included 711 patients who underwent unilateral TKA. They were divided into four groups: allogeneic transfusion group (group AL), autologous transfusion group (group AT), tranexamic acid group (group TA), and control group (group C). The primary outcome was rate of postoperative allogeneic blood transfusions. Secondary outcomes were postoperative hemoglobin and hematocrit levels, postoperative bleeding amount. RESULTS: Groups AT and AL did not exhibit a significant reduction in postoperative allogenic blood transfusion rate compared to group C (28/108 vs. 20/108, p = 0.21 and 37/159 vs. 34/159, p = 0.78 respectively). However, group TA demonstrated a significantly lower rate of postoperative allogenic blood transfusions than group C (22/125 vs. 3/125, p = 0.0001). Postoperative hemoglobin and hematocrit levels were statistically higher in group TA than in group C. However, those levels in group AT and AL did not differ significantly from those of group C. CONCLUSION: Intra-operative prophylactic transfusions did not decrease postoperative anemia or additional postoperative transfusion compared to the control group in patients undergoing total knee arthroplasty. However, the group receiving tranexamic acid showed lower transfusion rate and higher levels of hemoglobin and hematocrit.

Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain.

Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain's biology - the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Pan-EGFR Inhibitor Dacomitinib Resensitizes Paclitaxel and Induces Apoptosis via Elevating Intracellular ROS Levels in Ovarian Cancer SKOV3-TR Cells.

Paclitaxel is still used as a standard first-line treatment for ovarian cancer. Although paclitaxel is effective for many types of cancer, the emergence of chemoresistant cells represents a major challenge in chemotherapy. Our study aimed to analyze the cellular mechanism of dacomitinib, a pan-epidermal growth factor receptor (EGFR) inhibitor, which resensitized paclitaxel and induced cell cytotoxicity in paclitaxel-resistant ovarian cancer SKOV3-TR cells. We investigated the significant reduction in cell viability cotreated with dacomitinib and paclitaxel by WST-1 assay and flow cytometry analysis. Dacomitinib inhibited EGFR family proteins, including EGFR and HER2, as well as its downstream signaling proteins, including AKT, STAT3, ERK, and p38. In addition, dacomitinib inhibited the phosphorylation of Bad, and combination treatment with paclitaxel effectively suppressed the expression of Mcl-1. A 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay revealed a substantial elevation in cellular reactive oxygen species (ROS) levels in SKOV3-TR cells cotreated with dacomitinib and paclitaxel, which subsequently mediated cell cytotoxicity. Additionally, we confirmed that dacomitinib inhibits chemoresistance in paclitaxel-resistant ovarian cancer HeyA8-MDR cells. Collectively, our research indicated that dacomitinib effectively resensitized paclitaxel in SKOV3-TR cells by inhibiting EGFR signaling and elevating intracellular ROS levels.

Natal factors affecting developmental defects of enamel in preterm infants: a prospective cohort study.

This study investigated natal factors influencing developmental defects of enamel (DDE) in premature infants using a newly refined preterm developmental defects of enamel (PDDE) index. Dental examinations were conducted on a cohort of 118 preterm infants (average age 3.5 ± 1.4 years) to record PDDE scores, while reviewing their medical records to examine natal factors. According to the logistic regression analysis, factors related to DDE prevalence were advanced maternal age, gestational age < 28 weeks, birth weight < 1000 g, 1 min APGAR score < 7, and hospitalization period > 2 months, which were significantly higher by 2.91, 5.53, 7.63, 10.02, and 4.0 times, respectively. According to regression analysis with generalized linear models, the PDDE scores were approximately 7.65, 4.96, and 15.0 points higher in premature children diagnosed with bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, respectively. When endotracheal intubation was performed, the PDDE score was 5.06 points higher. The prevalence of PDDE was primarily observed bilaterally in the maxillary anterior teeth. Extremely preterm infants showed significantly delayed tooth eruption, suggesting that the influence of gestational age on dental development rates. Identifying the factors related to DDE in premature children can inform early dental interventions to support the oral health of high-risk children.

Post-treatment Radiographic Severity and Mortality in Mycobacterium avium Complex Pulmonary Disease.

Rationale: Imaging studies are widely performed when treating Mycobacterium avium complex pulmonary disease (MAC-PD); however, the clinical significance of post-treatment radiographic change is unknown. Objectives: To determine whether a deep neural network trained with pulmonary tuberculosis could adequately score the radiographic severity of MAC-PD and then to examine relationships between post-treatment radiographic severity and its change from baseline and long-term prognosis. Methods: We retrospectively collected chest radiographs of adult patients with MAC-PD treated for ⩾6 months at baseline and at 3, 6, 9, and 12 months of treatment. We correlated the radiographic severity score generated by a deep neural network with visual and clinical severity as determined by radiologists and mycobacterial culture status, respectively. The associations between the score, improvement from baseline, and mortality were analyzed using Cox proportional hazards regression. Results: In total, 342 and 120 patients were included in the derivation and validation cohorts, respectively. The network's severity score correlated with radiologists' grading (Spearman coefficient, 0.40) and mycobacterial culture results (odds ratio, 1.02; 95% confidence interval [CI], 1.0-1.05). A significant decreasing trend in the severity score was observed over time (P < 0.001). A higher score at 12 months of treatment was independently associated with higher mortality (adjusted hazard ratio, 1.07; 95% CI, 1.03-1.10). Improvements in radiographic scores from baseline were associated with reduced mortality, regardless of culture conversion (adjusted hazard ratio, 0.42; 95% CI, 0.22-0.80). These findings were replicated in the validation cohort. Conclusions: Post-treatment radiographic severity and improvement from baseline in patients with MAC-PD were associated with long-term survival.

Mitochondrial E3 ligase MARCH5 is a safeguard against DNA-PKcs-mediated immune signaling in mitochondria-damaged cells.

Mitochondrial dysfunction is important in various chronic degenerative disorders, and aberrant immune responses elicited by cytoplasmic mitochondrial DNA (mtDNA) may be related. Here, we developed mtDNA-targeted MTERF1-FokI and TFAM-FokI endonuclease systems to induce mitochondrial DNA double-strand breaks (mtDSBs). In these cells, the mtDNA copy number was significantly reduced upon mtDSB induction. Interestingly, in cGAS knockout cells, synthesis of interferon ß1 and interferon-stimulated gene was increased upon mtDSB induction. We found that mtDSBs activated DNA-PKcs and HSPA8 in a VDAC1-dependent manner. Importantly, the mitochondrial E3 ligase MARCH5 bound active DNA-PKcs in cells with mtDSBs and reduced the type І interferon response through the degradation of DNA-PKcs. Likewise, mitochondrial damage caused by LPS treatment in RAW264.7 macrophage cells increased phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA in a DNA-PKcs-dependent manner. Accordingly, in March5 knockout macrophages, phospho-HSPA8 levels and the synthesis of mIFNB1 mRNA were prolonged after LPS stimulation. Together, cytoplasmic mtDNA elicits a cellular immune response through DNA-PKcs, and mitochondrial MARCH5 may be a safeguard to prevent persistent inflammatory reactions.

Tephrosin Suppresses the Chemoresistance of Paclitaxel-Resistant Ovarian Cancer via Inhibition of FGFR1 Signaling Pathway.

Ovarian cancer is the leading cause of death among gynecologic cancers. Paclitaxel is used as a standard first-line therapeutic agent for ovarian cancer. However, chemotherapeutic resistance and high recurrence rates are major obstacles to treating ovarian cancer. We have found that tephrosin, a natural rotenoid isoflavonoid, can resensitize paclitaxel-resistant ovarian cancer cells to paclitaxel. Cell viability, immunoblotting, and a flow cytometric analysis showed that a combination treatment made up of paclitaxel and tephrosin induced apoptotic death. Tephrosin inhibited the phosphorylation of AKT, STAT3, ERK, and p38 MAPK, all of which simultaneously play important roles in survival signaling pathways. Notably, tephrosin downregulated the phosphorylation of FGFR1 and its specific adapter protein FRS2, but it had no effect on the phosphorylation of the EGFR. Immunoblotting and a fluo-3 acetoxymethyl assay showed that tephrosin did not affect the expression or function of P-glycoprotein. Additionally, treatment with N-acetylcysteine did not restore cell cytotoxicity caused by a treatment combination made up of paclitaxel and tephrosin, showing that tephrosin did not affect the reactive oxygen species scavenging pathway. Interestingly, tephrosin reduced the expression of the anti-apoptotic factor XIAP. This study demonstrates that tephrosin is a potent antitumor agent that can be used in the treatment of paclitaxel-resistant ovarian cancer via the inhibition of the FGFR1 signaling pathway.

Evaluating the Landscape of Personal Health Records in Korea: Results of the National Health Informatization Survey.

OBJECTIVES: This study examined the adoption and utilization of personal health records (PHR) across Korean medical institutions using data from the 2020 National Health and Medical Informatization Survey. METHODS: Spearheaded by the Ministry of Health and Welfare and prominent academic societies, this study surveyed PHR utilization in 574 medical institutions. RESULTS: Among these institutions, 84.9% (487 hospitals) maintained medical portals. However, just 14.1% (81 hospitals) had web-based or mobile PHRs, with 66.7% (28 of 42) of tertiary care hospitals adopting them. Tertiary hospitals led in PHR services: 87.8% offered certification issuance, 51.2% provided educational information, 63.4% supported online payment, and 95.1% managed appointment reservations. In contrast, general and smaller hospitals had lower rates. Online medical information viewing was prominent in tertiary hospitals (64.3%). Most patients accessed test results via PHRs, but other data types were less frequent, and only a few allowed downloads. Despite the widespread access to medical data through PHRs, integration with wearables and biometric data transfers to electronic medical records remained low, with limited plans for expansion in the coming three years. CONCLUSIONS: Approximately two-thirds of the surveyed medical institutions provided PHRs, but hospitals and clinics in charge of community care had very limited PHR implementation. Government-led leadership is required to invigorate the use of PHRs in medical institutions.

A map matching algorithm based on modified hidden Markov model considering time series dependency over larger time span.

With the advancement of geopositioning systems and mobile devices, much research with geopositioning data are currently ongoing. Along with the research applications, map matching is a technology that infers the actual position of error-prone trajectory data. It is a core preprocessing technique for trajectory data. Among various map matching algorithms, map matching using Hidden Markov Model (HMM) has gained high attention. However, the HMM model simplifies the dependency of time series data excessively, which leads to inferring incorrect matching results for various situations. For example, complex road relationships or movement patterns, such as in urban areas, or serious observation errors and sampling intervals make matching more difficult. In this research, we propose a new algorithm called trendHMM map matching, which complements the assumptions of HMM. This algorithm considers a wider range of dependencies of geopositioning data by incorporating the movements of neighboring data into the matching process. For this purpose, the concept of the window containing adjacent geopositioning data is introduced. Thus trendHMM can utilize relationships among continuous geopositioning data and showed considerable enhancement over HMM-based algorithm. Through experiments, we demonstrated that trendHMM map matching provides more accurate results than the existing HMM map matching for various environments and geopositioning data sets. Our trendHMM algorithm shows up to 17.58% of performance enhancement compared to HMM based one in terms of Route Mismatch Fraction.

Impact of lung cancer screening with low-dose chest computed tomography on an older population: a retrospective cohort study.

Background: The older population is at high risk of lung cancer (LC). However, the importance of lung cancer screening (LCS) in this population is rarely investigated. Herein, we evaluated the effect of LCS with low-dose computed tomography (LDCT) in the older population. Methods: This retrospective cohort study was conducted in a single center and included patients aged 70-80 years who had undergone LCS with LDCT. They were categorized into the early 70s (70-74 years) and late 70s (75-80 years) groups based on their age. Using propensity score matching, the control group included patients with non-screening-detected LC from an LC cohort. LC detection, characteristics, and treatment were compared between the early and late 70s groups and between screening-detected LC and non-screening-detected LC. Results: The study included 1,281 participants who underwent LDCT for LCS, of whom 1,020 were in their early 70s and 261 in their late 70s. Among the screening groups, 87.7% of the patients were ever-smokers. The overall LC detection rate was 2.8%. Interestingly, the LC detection rate in the late 70s group was similar to that in the early 70s group (3.4% vs. 2.7%, P=0.485). Furthermore, the incidence of LC was 6.1 cases and 8.3 cases per 1,000 person-years in the early 70s and late 70s groups, respectively (P=0.428). When comparing LC characteristics, patients with screening-detected LC showed a higher proportion of stage I LC (52.8% vs. 30.6%, P=0.010) and a lower proportion of stage IV LC (19.4% vs. 42.2%, P=0.010) than those with non-screening-detected LC. Moreover, 80.6% of patients with screening-detected LC received appropriate tumor reduction treatment based on the cancer stage. Conclusions: In the older population, LCS using LDCT showed remarkable detection of LC, with a higher proportion of cases detected at an early stage.

Comprehensive Analysis of NKX3.2 in Liver Hepatocellular Carcinoma by Bigdata.

Background and Objectives: The gene NKX3.2 plays a role in determining cell fate during development, and mutations of NKX3.2 have been studied in relation to human skeletal diseases. However, due to the lack of studies on the link between NKX3.2 and cancer, we aimed to provide insights into NKX3.2 as a new prognostic biomarker for liver hepatocellular carcinoma (LIHC). Materials and Methods: The clinical significance of LIHC was investigated using open gene expression databases. We comprehensively analyzed NKX3.2 expression in LIHC using Gene Expression Profiling Interactive Analysis 2, Tumor Immune Estimation Resource (TIMER), and Kaplan-Meier plotter databases. Then, we investigated the association between NKX3.2 expression and tumor-infiltrating immune cells (TIICs). Results: NKX3.2 expression was higher in the primary tumor group compared to the normal group, and expression was higher in fibrolamellar carcinoma (FLC) compared to other subtypes. When the prognostic value of NKX3.2 was evaluated, highly expressed NKX3.2 significantly improved the overall survival and had an unfavorable prognosis. In addition, NKX3.2 expression was associated with immune cell infiltration. Patients with low gene expression and high macrophage expression had a poorer survival rate than those with low NKX3.2 and low macrophage expression (p = 0.0309). Conclusions: High NKX3.2 expression may induce poorer prognosis in LIHC. In addition, these findings can be used as basic data due to the lack of available related research. However, further in vivo studies are essential to gain a deeper understanding of the biological role of NKX3.2 in LIHC and its potential implications for cancer development and progression.

Mitigating Age-Related Ovarian Dysfunction with the Anti-Inflammatory Agent MIT-001.

Ovarian aging is a major obstacle in assisted reproductive medicine because it leads to ovarian dysfunction in women of advanced age. Currently, there are no effective treatments to cure age-related ovarian dysfunction. In this study, we investigated the effect of MIT-001 on the function of aged ovaries. Young and old mice were utilized in this study. MIT-001 was intraperitoneally administered, and the number of follicles and oocytes was analyzed. Each group was then retrieved for RNA and protein isolation. Total RNA was subjected to mRNA next-generation sequencing. Protein extracts from ovarian lysates were used to evaluate various cytokine levels in the ovaries. MIT-001 enhanced follicles and the number of oocytes were compared with non-treated old mice. MIT-001 downregulated immune response-related transcripts and cytokines in the ovaries of old mice. MIT-001 modulates the immune complex responsible for generating inflammatory signals and has the potential to restore the function of old ovaries and improve female fertility.