The role of 2'-5'-oligoadenylate synthase-like protein (OASL1) in biliary and hepatotoxin-induced liver injury in mice.

Following an injury, the liver embarks on a process that drives the accumulation and reformation of the extracellular matrix, leading to hepatic fibrosis. Type I interferons (IFNs), including IFN-α and IFN-ß, play a crucial role in averting chronic liver injury through the activation of IFN-stimulated genes (ISGs), which are instrumental in sculpting adaptive immunity. The role of 2'-5'-oligoadenylate synthase-like protein 1 (OASL1), an antiviral ISG, in the context of liver fibrosis remains to be elucidated. To elicit liver fibrosis, a diet containing 0.1% diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4) were employed to induce cholestatic- and hepatotoxin-mediated liver fibrosis, respectively. Histological analyses of both models revealed that OASL1-/- mice exhibited reduced liver damage and, consequently, expressed lower levels of fibrotic mediators, notably α-smooth muscle actin. OASL1-/- mice demonstrated significantly elevated IFN-α and IFN-ß mRNA levels, regulated by the IFN regulatory factor 7 (IRF7). Additionally, OASL1-/- ameliorated chronic liver fibrosis through the modulation of nuclear factor-κB (NF-κB) signaling. The effect of OASL1 on type I IFN production in acute liver damage was further explored and OASL1-/- mice consistently showed lower alanine transaminase levels and pro-inflammatory cytokines, but IFN-α and IFN-ß mRNA levels were upregulated, leading to amelioration of acute liver injury. Additionally, the study discovered that F4/80-positive cells were observed more frequently in OASL1-/- CCl4 acutely treated mice. This implies that there is a significant synergy in the function of macrophages and OASL1 deficiency. These results demonstrate that in instances of liver injury, OASL1 inhibits the production of type I IFN by modulating the NF-κB signaling pathway, thereby worsening disease.

Predicting Lung Cancer in Korean Never-Smokers With Polygenic Risk Scores.

In the last few decades, genome-wide association studies (GWAS) with more than 10,000 subjects have identified several loci associated with lung cancer and these loci have been used to develop novel risk prediction tools for cancer. The present study aimed to establish a lung cancer prediction model for Korean never-smokers using polygenic risk scores (PRSs); PRSs were calculated using a pruning-thresholding-based approach based on 11 genome-wide significant single nucleotide polymorphisms (SNPs). Overall, the odds ratios tended to increase as PRSs were larger, with the odds ratio of the top 5% PRSs being 1.71 (95% confidence interval: 1.31-2.23) using the 40%-60% percentile group as the reference, and the area under the curve (AUC) of the prediction model being of 0.76 (95% confidence interval: 0.747-0.774). The receiver operating characteristic (ROC) curves of the prediction model with and without PRSs as covariates were compared using DeLong's test, and a significant difference was observed. Our results suggest that PRSs can be valuable tools for predicting the risk of lung cancer.

Hepatocyte-Specific Casein Kinase 1 Epsilon Ablation Ameliorates Metabolic Dysfunction-Associated Steatohepatitis by Up-Regulating Tumor Necrosis Factor Receptor-Associated Factor 3 in Mice.

Casein kinase 1 epsilon (CK1ε), a member of the serine/threonine protein kinase family, is known to phosphorylate a broad range of substrates. However, its role in the development of chronic liver diseases remains elusive. This study aimed to investigate the role of CK1ε in the development and progression of metabolic dysfunction-associated steatohepatitis (MASH). Hepatocyte-specific CK1ε knockout (CK1εΔHEP) mice were generated by crossbreeding mice with floxed CK1ε alleles (CK1εfl/fl) and Cre-expressing albumin mice. Mice were fed either a Western diet (WD) or a methionine- and choline-deficient diet to induce MASH. CK1εΔHEP was associated with a decreased severity of WD- or methionine- and choline-deficient diet-induced MASH, as confirmed by reduced incidence of hepatic lesions and significantly lower levels of alanine aminotransferase, aspartate aminotransferase, and proinflammatory cytokine tumor necrosis factor (TNF)-α. CK1εΔHEP WD-fed mice exhibited significant amelioration of total cholesterol, triglycerides, and de novo lipogenic genes, indicating that CK1ε could influence lipid metabolism. CK1εΔHEP WD-fed mice showed significantly down-regulated TNF receptor-associated factor 3, phosphorylated (p) transforming growth factor-ß-activated kinase 1, p-TANK-binding kinase 1, and p-AKT levels, thereby affecting downstream mitogen-activated protein kinase signaling, indicating a potential mechanism for the observed rescue. Finally, pharmacologic inhibition of CK1ε with PF670462 improved palmitic acid-induced steatohepatitis in vitro and attenuated WD-induced metabolic profile in vivo. In conclusion, CK1ε up-regulates TNF receptor-associated factor 3, which, in turn, causes transforming growth factor-ß-activated kinase 1-dependent signaling, amplifies downstream mitogen-activated protein kinase signaling, modifies p-c-Jun levels, and exacerbates inflammation, all of which are factors in WD-induced metabolic dysfunction-associated steatotic liver disease.

Prenatal cigarette smoke exposure sensitizes acetaminophen-induced liver injury by modulating miR-34a-5p in male offspring mice.

Introduction: Cigarette smoke (CS) exacerbates the severity of diseases not only in lungs, but also in systemic organs having no direct contact with smoke. In addition, smoking during pregnancy can have severe health consequences for both the mother and the fetus. Therefore, our aim was to evaluate effects of prenatal exposure to CS on acetaminophen (APAP)-induced acute liver injury (ALI) in offspring. Methods: Female C57BL/6 mice on day 6 of gestation were exposed to mainstream CS (MSCS) at 0, 150, 300, or 600 µg/L for 2 h a day, 5 days a week for 2 weeks using a nose-only exposure system. At four weeks old, male offspring mice were injected intraperitoneally with a single dose of APAP at 300 mg/kg body weight to induce ALI. Results: Maternal MSCS exposure significantly amplified pathological effects associated with ALI as evidenced by elevated serum alanine aminotransferase levels, increased hepatocellular apoptosis, higher oxidative stress, and increased inflammation. Interestingly, maternal MSCS exposure reduced microRNA (miR)-34a-5p expression in livers of offspring. Moreover, treatment with a miR-34a-5p mimic significantly mitigated the severity of APAP-induced hepatotoxicity. Overexpression of miR-34a-5p completely abrogated adverse effects of maternal MSCS exposure in offspring with ALI. Mechanistically, miR-34a-5p significantly decreased expression levels of hepatocyte nuclear factor 4 alpha, leading to down-regulated expression of cytochrome P450 (CYP)1A2 and CYP3A11. Discussion: Prenatal exposure to MSCS can alter the expression of miRNAs, even in the absence of additional MSCS exposure, potentially increasing susceptibility to APAP exposure in male offspring mice.

Cholesin and GPR146 in Modulating Cholesterol Biosynthesis.

BACKGROUND: Cholesterol homeostasis in the human body is a crucial process that involves a delicate balance between dietary cholesterol absorption in the intestine and de novo cholesterol synthesis in the liver. Both pathways contribute significantly to the overall pool of cholesterol in the body, influencing plasma cholesterol levels and impacting cardiovascular health. Elevated absorption of cholesterol in the intestines has a suppressive impact on the synthesis of cholesterol in the liver, serving to preserve cholesterol balance. Nonetheless, the precise mechanisms driving this phenomenon remain largely unclear. SUMMARY: This review aimed to discuss the previously unrecognized role of cholesin and GPR146 in the regulation of cholesterol biosynthesis, providing a novel conceptual framework for understanding cholesterol homeostasis. KEY MESSAGES: The discovery of cholesin, a novel protein implicated in the regulation of cholesterol homeostasis, represents a significant advancement in our understanding of cholesterol biosynthesis and its associated pathways. The cholesin-GPR146 axis could have profound implications across various therapeutic areas concerning abnormal cholesterol metabolism, offering new hope for patients and improving overall healthcare outcomes.

Evaluation of Droplet Digital PCR for the Detection of BRAF V600E in Fine-Needle Aspiration Specimens of Thyroid Nodules.

Background: Droplet digital (dd)PCR is a new-generation PCR technique with high precision and sensitivity; however, the positive and negative droplets are not always effectively separated because of the "rain" phenomenon. We aimed to develop a practical optimization and evaluation process for the ddPCR assay and to apply it to the detection of BRAF V600E in fine-needle aspiration (FNA) specimens of thyroid nodules, as an example. Methods: We optimized seven ddPCR parameters that can affect "rain." Analytical and clinical performance were analyzed based on histological diagnosis after thyroidectomy using a consecutive prospective series of 242 FNA specimens. Results: The annealing time and temperature, number of PCR cycles, and primer and probe concentrations were found to be more important considerations for assay optimization than the denaturation time and ramp rate. The limit of blank and 95% limit of detection were 0% and 0.027%, respectively. The sensitivity of ddPCR for histological papillary thyroid carcinoma (PTC) was 82.4% (95% confidence interval [CI], 73.6%-89.2%). The pooled sensitivity of BRAF V600E in FNA specimens for histological PTC was 78.6% (95% CI, 75.9%-81.2%, I2=60.6%). Conclusions: We present a practical approach for optimizing ddPCR parameters that affect the separation of positive and negative droplets to reduce rain. Our approach to optimizing ddPCR parameters can be expanded to general ddPCR assays for specific mutations in clinical laboratories. The highly sensitive ddPCR can compensate for uncertainty in cytological diagnosis by detecting low levels of BRAF V600E.

Changes in the Remaining Iliac Artery According to Retrograde Flow after Aorto-Femoral Bypass in Abdominal Aortic Aneurysms.

BACKGROUND: Considering a patient's anatomy and vascular conditions, aorto-femoral bypass is a treatment approach for the open repair of abdominal aortic aneurysms. This study aimed at evaluating changes in the remnant iliac artery and their correlation with the preservation state of retrograde flow from femoral anastomosis. METHODS: Of 221 patients who underwent abdominal aortic aneurysm surgery between 2007 and 2022 in Pusan National University Hospital, 29 patients who underwent aorto-femoral bypass were included in this retrospective cohort study. Of these patients, 21 underwent aortobifemoral bypass and 8 underwent aortoiliac-and-femoral bypass. The change in size of the iliac artery from preoperative to postoperative and whether this difference in size depended on the status of postoperative retrograde flow were investigated. Additionally, factors affecting overall mortality and ischemic complications were identified. RESULTS: The median duration from operation to the last follow-up was 2069.5 days (about 5.7 years). The average age of the patients was 78.1 years, and the proportion of males was 75.9%. In cases of disappearance of postoperative retrograde flow from the femoral anastomosis, the postoperative iliac artery size was significantly reduced compared to its preoperative size (18.4 ± 18.9 mm vs. 13.2 ± 7.9 mm, respectively; P = 0.04). The group with maintained retrograde flow had significantly larger residual common iliac artery size than the group with disappearance of flow. (20.0 ± 28.0 mm vs. 14.6 ± 8.5 mm, respectively; P = 0.02). Disappearance of retrograde flow was a significant factor in the iliac artery size reduction after surgery (odds ratio, 2.5; 95% confidence interval, 1.9-5.3; P = 0.02). Three patients with maintained retrograde flow (18.8%) required intervention owing to an increase in the size of the iliac artery. The factors that significantly influenced overall death as analyzed by Cox proportional hazard regression were chronic obstructive pulmonary disease (hazard ratio, 36.8; 95% confidence interval, 1.6-870.0; P = 0.03), peripheral arterial occlusive disease (hazard ratio, 12.7; 95% confidence interval, 1.4-115.8; P = 0.02), and disappearance of retrograde flow (hazard ratio, 8.7; 95% confidence interval, 1.2-63.9; P = 0.03). CONCLUSIONS: Among the open repair methods for abdominal aortic aneurysms, if retrograde flow was not maintained through femoral anastomosis when aorto-femoral bypass was performed, the size of the remaining iliac artery decreased. However, loss of retrograde flow increased long-term mortality. When aorto-femoral bypass is performed, regular imaging follow-up is necessary at appropriate intervals to check the remnant iliac artery and retrograde flow.

Effects of public transportation use on non-exercise activity thermogenesis and health promotion: a mini-review.

PURPOSE: Public transportation (PT) systems significantly shape urban mobility and have garnered attention owing to their potential impact on public health, particularly the promotion of physical activity. Beyond their transportation functions, PT systems also affect daily energy expenditure through non-exercise activity thermogenesis (NEAT). This mini-review surveys the existing literature to explore the effects of PT use on NEAT levels and subsequent health outcomes. METHODS: A comprehensive literature search was conducted using the electronic databases PubMed, Google Scholar, and Web of Science. Keywords including "public transportation," "non-exercise activity thermogenesis," "physical activity," "health promotion," and related terms were used to identify relevant studies. RESULTS: This review highlights the multifaceted relationship between PT use and health promotion, emphasizing the potential benefits and challenges of increasing NEAT through public transit utilization. Overall, the findings suggest that PT use contributes positively to NEAT levels, and thus improves health outcomes. However, the extent of this impact may vary depending on individual and contextual factors. CONCLUSION: Interventions promoting active transportation modes, including public transit, hold promise for addressing sedentary behavior and fostering healthier lifestyles at the population level.

Staged angioplasty using a full-length balloon catheter to achieve maturation of arteriovenous fistulas.

PURPOSE: To evaluate the efficacy of staged full-length balloon-assisted maturation (BAM) for the maturation of arteriovenous fistulas (AVFs) on entire segmental veins, including stenosis, causing primary AVF failure. METHODS: This study included patients who underwent AVF surgery using an autogenous vein between February 2020 and June 2021 and received staged angioplasty with a full-length balloon catheter. To minimize balloon overlap and the risk of barotrauma to the immature vein, serial-staged upsizing balloon angioplasty with a long balloon catheter covering the entire vein segment was employed approximately 2 weeks apart. RESULTS: Twenty-three patients (mean age, 69.50 years; mean follow-up, 620.62 days) with average diameters of the radial artery and cephalic vein at 2.14 ± 0.5 mm and 2.43 ± 0.5 mm, respectively, were enrolled. In the first procedure, the average AVF diameter and flow were 4.03 ± 0.57 mm and 438.08 ± 220.95 mL/min, respectively, with juxta-anastomotic stenosis (JAS) present in 61.5% of cases. After staged full-length BAM, the average fistula diameter and flow improved to 5.95 ± 0.86 mm and 717.52 ± 305.95 mL/min, respectively. Maturation was achieved in 87% of the cases. No hematomas or ruptures occurred around the arterialized veins. Despite successful maturation and cannulation, 65.2% of the patients required additional percutaneous transluminal angioplasty (PTA) during the follow-up period. The necessity for PTA was determined by the presence of JAS prior to the first staged full-length BAM, with an odds ratio of 11.74 (95% confidence interval: 1.31-104.96, P = 0.03). CONCLUSION: Staged full-length BAM can be safely used in patients with small veins requiring further maturation. Most patients achieved successful cannulation following maturation without post-procedural complications. CLINICAL SIGNIFICANCE: Staged full-length BAM is a safe and effective method for enhancing maturation in patients with underdeveloped small veins.

Analysis of football research trends using text network analysis.

This study was aimed to identify football research trends in various periods. A total of 30,946 football papers were collected from a representative academic database and search engine, the 'Web of Science'. Keyword refinement included filtering nouns, establishing synonyms and thesaurus, and excluding conjunctions, and the Cyram's Netminer 4.0 software was used for network analysis. A centrality analysis was conducted by extracting the words corresponding to the top 2% of the main research topics to obtain the degree and eigenvector centralities. The most frequently mentioned research keywords were injury, performance, and club. Keyword performance showed the highest degree centrality (0.294) and keyword world and cup showed the highest eigenvector centrality (0.710). The keyword with the highest eigenvector degree changed from injury in the 1990s and world in the 2000s to cup since the 2010s. Although various studies on football injuries have been conducted, research on the sport itself has recently been conducted. This study provides fundamental information on football trends from research published over the past 30 years.

Tongue patch angioplasty for small-caliber vein segments directly connected to juxta-anastomotic stenosis.

This study introduces a surgical method to increase the size of small vessels in patients with juxta-anastomosis stenosis (JAS) requiring full-length dissection. The small-caliber segment that is adjacent to JAS is usually expanded using balloon angioplasty or surgically resected. After resection, if the cannulation site is sufficient, only the arterial anastomosis is moved proximally; otherwise, it is replaced with a prosthetic graft. Herein, we describe the cases of two 60- and 34-year-old men with left brachio-basilar and left radiocephalic fistulas, respectively. The first and second patients needed transposition and superficialization, respectively, both of which required full-length vessel dissection. Both patients developed JAS with a long, small-caliber segment, leaving no space for arterial needle cannulation. A tongue patch with a graft on the bottom and a native vein on the top was used to resolve the JAS and make the native vein the needle cannulation site. In our cases, this method was effective for more than 2 years without adverse events in the particular surgical area. Although this method had a complicated indication, it could help ensure a sufficiently long area of the native vein for cannulation.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Rejoining Veins for Forced Maturation of Small-Caliber Arteriovenous Fistula.

BACKGROUND: To evaluate the efficacy of rejoining mainstream and accessory veins for forced maturation of autogenous arteriovenous fistula (AVF). METHODS: Twenty-three patients who underwent forced maturation through vein rejoining between January 2018 and September 2022 were included. In cases where AVF maturation failure due to the presence of accessory veins, rejoining was primarily considered when distinguishing the main branch becomes challenging. This difficulty typically occurs when the sizes of the 2 vessels are nearly equal and the combined diameters of these veins exceed 6 mm. RESULTS: The mean age and follow-up duration were 57.39 ± 16.22 years and 965.65 ± 573.42 days, respectively. Rejoining of both arterial and venous cannulation sites was performed in 11 patients (47.8%), and rejoining of only the venous cannulation site or only the arterial cannulation site was performed in 11 patients (47.8%) and 1 patient (4.3%), respectively. The mean vein size was 0.35 ± 0.06 cm before rejoining and 0.69 ± 0.07 cm after surgery, indicating a significant increase in size (P < 0.01), whereas the flow did not change significantly following rejoining surgery. Maturation and cannulation success was 100%. The 1-year primary patency rate after surgery was 82.0%. During the follow-up period, 34.8% of the patients required additional percutaneous transluminal angioplasty to maintain patency, and 2 patients (11.8%) had stenosis in the rejoined section. CONCLUSIONS: Rejoining surgery is an effective method for achieving AVF maturation in patients with accessory veins when identification of the mainstream vein is difficult, and this method may be considered when achieving maturation by sacrificing 1 vein is expected to be challenging.

An atypical case involving real, ghost, and pseudo-ghost images on a panoramic radiograph.

Purpose: This report presents a unique case featuring real, ghost, and pseudo-ghost images on the panoramic radiograph of a patient wearing earrings. It also explains the formation of these images in an easy-to-understand manner. Material and Methods: One real image and two ghost images appeared on each side of a panoramic radiograph of a patient wearing earrings on both sides. Of the two ghost images on each side, one was considered a typical ghost image and the other was considered a ghost-like real image (pseudo-ghost image). The formation zones of the real, double, and ghost images were examined based on the path and angles of the X-ray beam from the Planmeca ProMax. To simulate the pseudo-ghost and typical ghost images on panoramic radiography, a radiopaque marker was affixed to the right mandibular condyle of a dry mandible, and the position of the mandible was adjusted accordingly. Results: The center of rotation of the Planmeca ProMax extended beyond the jaw area, and the area of double image formation also reached beyond the jaw. The radiopaque-marked mandibular condyle, situated in the outwardly extending area of double image formation, exhibited triple images consisting of real, double (pseudo-ghost), and ghost images. These findings helped to explain the image formation associated with the patient's earrings observed in the panoramic radiograph. Conclusion: Dentists must understand the characteristics and principles of the panoramic equipment they use and apply this understanding to taking and interpreting panoramic radiographs.

Effects of Polybutylene Succinate Content on the Rheological Properties of Polylactic Acid/Polybutylene Succinate Blends and the Characteristics of Their Fibers.

Polylactic acid (PLA) and polybutylene succinate (PBS) are gaining prominence as environmentally friendly alternatives to petroleum-based polymers due to their inherent biodegradability. For their textile applications, this research is focused on exploring the effects of PBS content on the rheological properties of PLA/PBS blends and the characteristics of PLA/PBS blend fibers. PLA/PBS blends and fibers with varying PBS contents (0 to 10 wt.%) were prepared using melt-blending and spinning methods. Uniform morphologies of the PLA/PBS blends indicated that PBS was compatible with PLA, except at 10% PBS content, where phase separation occurred. The introduction of PBS reduced the complex viscosity of the blends, influencing fiber properties. Notably, PLA/PBS fibers with 7% PBS exhibited improved crystallinity, orientation factor, and elasticity (~16.58%), with a similar tensile strength to PLA fiber (~3.58 MPa). The results suggest that an optimal amount of PBS enhances alignment along the drawing direction and improves the molecular motion in PLA/PBS blend fiber. This study highlights the potential of strategically blending PBS to improve PLA fiber characteristics, promising advancement in textile applications.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

The evidence-based multifaceted roles of hepatic stellate cells in liver diseases: A concise review.

Hepatic stellate cells (HSCs) play central roles in liver disease pathogenesis, spanning steatosis to cirrhosis and hepatocellular carcinoma. These cells, located in the liver's sinusoidal space of Disse, transition from a quiescent, vitamin A-rich state to an activated, myofibroblast-like phenotype in response to liver injury. This activation results from a complex interplay of cytokines, growth factors, and oxidative stress, leading to excessive collagen deposition and liver fibrosis, a hallmark of chronic liver diseases. Recently, HSCs have gained recognition for their dynamic, multifaceted roles in liver health and disease. Attention has shifted toward their involvement in various liver conditions, including acute liver injury, alcoholic and non-alcoholic fatty liver disease, and liver regeneration. This review aims to explore diverse functions of HSCs in these acute or chronic liver pathologies, with a focus on their roles beyond fibrogenesis. HSCs exhibit a wide range of actions, including lipid storage, immunomodulation, and interactions with other hepatic and extrahepatic cells, making them pivotal in the hepatic microenvironment. Understanding HSC involvement in the progression of liver diseases can offer novel insights into pathogenic mechanisms and guide targeted therapeutic strategies for various liver conditions.

Sulfation of chondroitin and bile acids converges to antagonize Wnt/ß-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis.

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology. 3'-Phosphoadenosine 5'-phosphosulfate (PAPS) synthase 2 (PAPSS2) is the primary enzyme to generate the universal sulfonate donor PAPS. The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli (APC) mutation-promoted colonic carcinogenesis has not been reported. Here, we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages, and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer. Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout (ApcΔgut-HetPapss2Δgut) mice were created, and the phenotypes were compared to the spontaneous intestinal tumorigenesis of ApcΔgut-Het mice. ApcΔgut-HetPapss2Δgut mice were more sensitive to gut tumorigenesis, which was mechanistically accounted for by the activation of Wnt/ß-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor (FXR)-transducin-like enhancer of split 3 (TLE3) gene regulatory axis. Chondroitin sulfate supplementation in ApcΔgut-HetPapss2Δgut mice alleviated intestinal tumorigenesis. In summary, we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/ß-catenin signaling. Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

Enhancing the Reliability of PMP22 Copy Number Variation Detection with an Inherited Peripheral Neuropathy Panel.

The utility of the next-generation sequencing (NGS) panel could be increased in hereditary peripheral neuropathies, given that the duplication of PMP22 is a major abnormality. In the present study, the analytical performance of an algorithm for detecting PMP22 copy number variation (CNV) from the NGS panel data was evaluated. The NGS panel covers 141 genes, including PMP22 and five genes within 1.5-megabase duplicated region at 17p11.2. CNV calling was performed using a laboratory-developed algorithm. Among the 92 cases subjected to targeted NGS panel from March 2018 to January 2021, 26 were suggestive of PMP22 CNV. Multiplex ligation-dependent probe amplification analysis was performed in 58 cases, and the results were 100% concordant with the NGS data (23 duplications, 2 deletions, and 33 negatives). Analytical performance of the pipeline was further validated by another blind data set, including 14 positive and 20 negative samples. Reliable detection of PMP22 CNV was possible by analyzing not only PMP22 but also the adjacent genes within the 1.5-megabase region of 17p11.2. On the basis of the high accuracy of CNV calling for PMP22, the testing strategy for diagnosis of peripheral polyneuropathies could be simplified by reducing the need for multiplex ligation-dependent probe amplification.

Penile Erection Morphometry: The Need for a Novel Approach.

For many males, sexual function holds significant value in determining their quality of life. Despite the importance of male erectile function, no quantitative method to measure it accurately is currently available. Standardized assessment methods such as RigiScan™, International Index of Erectile Function (IIEF-5), and the stamp test are used to evaluate sexual function, but those methods cannot repetitively and quantitatively measure erectile function. Only direct measurement can quantitatively assess the shape of an erect penis. This paper presents the essential requirements for developing an ideal measurement method for penile erection. It also introduces current approaches for diagnosing male sexual function and reviews ongoing research to quantitatively measure erectile function. The paper further summarizes and analyzes the advantages and disadvantages of each method with respect to the essential requirements. Finally, the paper discusses the future direction toward the development of Penile Erection Morphometry.