Enhanced Expression of Glycolytic Enzymes and Succinate Dehydrogenase Complex Flavoprotein Subunit A by Mesothelin Promotes Glycolysis and Mitochondrial Respiration in Myeloblasts of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from the bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, a higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to the reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating the acquisition of a rapid supply of ATP for proliferation in AML. Therefore, the targeting of mesothelin presents a potentially promising approach to mitigating the progression of AML through the inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Bilateral epididymal tuberculosis causing abscess formation and male infertility: a case report and literature review.

Background: Epididymal tuberculosis (TB) is an uncommon form of TB, although it is known to develop frequently in the male reproductive system. Infertility is rare but important among subsequent possible complications caused by the disease, particularly in young males. Moreover, it is difficult to differentiate epididymal TB from other epididymo-testicular diseases. Herein, we report a rare case of a young patient recently diagnosed with bilateral epididymal TB causing male infertility. Case Description: We report the case of a 37-year-old patient who presented with left testicular pain and swelling lasting for about 8 months. He had no comorbidities, including pulmonary TB. Additionally, he had no children and was worried about infertility. Physical examination revealed a firm and tender mass, which was palpable in the left epididymal area, measuring 3.5 cm × 2.2 cm in diameter. Acid-fast bacilli staining and polymerase chain reaction of the urine were negative. Semen analysis showed no sperm in the semen, implying azoospermia diagnosis. Scrotal ultrasonography was suggestive of severe left epididymitis with abscess formation without abnormal appearance of the testicle. Due to persistent testicular pain, intermittent fever, and severe epididymitis with abscess formation, the patient underwent epididymectomy. Surgical exploration of the testicle revealed a severely swollen and firm epididymis with abscess materials and hard and dilated vas deferens connected to the epididymis, implying severe inflammatory reactions. The histopathological examination revealed chronic granulomatous inflammation with caseous necrosis in the epididymis tissue. According to histopathological results, the patient was treated with anti-TB pharmacological treatment. About 1 month after the surgery, he presented with pain in the right testicular area, implying bilateral TB epididymis. After completion of the pharmacological treatment, the patient had no complaints, such as pain or swelling in both testicular areas. Conclusions: Physicians should consider the possibility of epididymal TB in patients with persistent testicular symptoms for early diagnosis. When a definitive diagnosis of epididymal TB is established, or clinically suspected, immediate treatment initiation, including pharmacological and, if needed, surgical treatment, should be performed to prevent subsequent complications, including abscess formation or male infertility, particularly in young males.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea.

BACKGROUND: Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study. METHODS: Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53. RESULTS: CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history. CONCLUSIONS: Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

[Radiologic Manifestations of Pulmonary Nuclear Protein in Testis Midline Carcinoma: A Case Report]. / 폐에 발생한 ê³ í™˜ 핵단백질 ì •ì¤‘ì„ ì•”ì˜ ì˜ìƒì˜í•™ì  소견: 증례 ë³´ê³ .

Nuclear portein in testis (NUT) midline carcinoma is a very rare and low-differentiating malignant epithelial tumor that differentiates very aggressively and has poor prognosis. NUT midline carcinoma occurring in the lungs in particular can be confused with other cancers because few cases have been reported in Korea to date and can show various histological forms. Reports of radiology findings are very rare worldwide. Here we report the imaging findings of pulmonary NUT midline carcinoma in a 25-year-old female along with pathological findings.

Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Effects of Farrerol in a Mouse Model of Obstructive Uropathy.

Obstructive uropathy is a clinical condition that can lead to chronic kidney disease. However, treatments that can prevent the progression of renal injury and fibrosis are limited. Farrerol (FA) is a natural flavone with potent antioxidant and anti-inflammatory properties. Here, we investigated the effect of FA on renal injury and fibrosis in a mouse model of unilateral ureteral obstruction (UUO). Mice underwent a sham or UUO operation and received intraperitoneal injections of FA (20 mg/kg) daily for 8 consecutive days. Histochemistry, immunohistochemistry and immunofluorescence staining, TdT-mediated dUTP nick end labeling assay, Western blotting, gene expression analysis, and biochemical tests were performed. FA attenuated renal dysfunction (p < 0.05) and ameliorated renal tubular injury (p < 0.01) and interstitial fibrosis (p < 0.001) in UUO mice. FA alleviated 4-hydroxynonenal expression (p < 0.001) and malondialdehyde levels (p < 0.01) by regulating pro-oxidant and antioxidant enzymes. Apoptosis in the kidneys of UUO mice was inhibited by FA (p < 0.001), and this action was accompanied by decreased expression of cleaved caspase-3 (p < 0.01). Moreover, FA alleviated pro-inflammatory cytokine production (p < 0.001) and macrophage infiltration (p < 0.01) in the kidneys of UUO mice. These results suggest that FA ameliorates renal injury and fibrosis in the UUO model by inhibiting oxidative stress, apoptosis, and inflammation.

Dynamic landscape of long noncoding RNAs during leaf aging in Arabidopsis.

Leaf senescence, the last stage of leaf development, is essential for whole-plant fitness as it marks the relocation of nutrients from senescing leaves to reproductive or other developing organs. Temporally coordinated physiological and functional changes along leaf aging are fine-tuned by a highly regulated genetic program involving multi-layered regulatory mechanisms. Long noncoding RNAs (lncRNAs) are newly emerging as hidden players in many biological processes; however, their contribution to leaf senescence has been largely unknown. Here, we performed comprehensive analyses of RNA-seq data representing all developmental stages of leaves to determine the genome-wide lncRNA landscape along leaf aging. A total of 771 lncRNAs, including 232 unannotated lncRNAs, were identified. Time-course analysis revealed 446 among 771 developmental age-related lncRNAs (AR-lncRNAs). Intriguingly, the expression of AR-lncRNAs was regulated more dynamically in senescing leaves than in growing leaves, revealing the relevant contribution of these lncRNAs to leaf senescence. Further analyses enabled us to infer the function of lncRNAs, based on their interacting miRNA or mRNA partners. We considered functionally diverse lncRNAs including antisense lncRNAs (which regulate overlapping protein-coding genes), competitive endogenous RNAs (ceRNAs; which regulate paired mRNAs using miRNAs as anchors), and mRNA-interacting lncRNAs (which affect the stability of mRNAs). Furthermore, we experimentally validated the senescence regulatory function of three novel AR-lncRNAs including one antisense lncRNA and two mRNA-interacting lncRNAs through molecular and phenotypic analyses. Our study provides a valuable resource of AR-lncRNAs and potential regulatory networks that link the function of coding mRNA and AR-lncRNAs. Together, our results reveal AR-lncRNAs as important elements in the leaf senescence process.

Zebrafish EEG predicts the efficacy of antiepileptic drugs.

Background: Pharmacological evaluation of antiepileptic drugs (AEDs) using mammalian animals takes long time and is expensive. The zebrafish is a species commonly used to study brain functions, neurological diseases, and drug toxicity, and attracts more attention as an alternative animal model to substitute or supplement mammalian animals in drug development. Electroencephalogram (EEG) is a key indicator for diagnosing brain diseases such as epilepsy, by directly measuring the brain activity. We propose a novel method for pharmacological evaluation of AEDs based on EEG from adult zebrafish, which allows researchers to select more clinically valuable drugs at the early stage of AED screening. Methods: To evaluate the efficacy of AEDs, zebrafish EEG signals were measured after administering six AEDs (valproate acid, gabapentin, ethosuximide, oxcarbazepine, tiagabine, and topiramate) at various doses to pentylenetetrazol (PTZ)-induced seizure models. The change in seizure activity was investigated according to doses. The antiepileptic effect was determined by observing a significant decrease in at least one out of three indicators of the number, total duration, and mean duration of ictal events. Results: Using EEG signals from adult zebrafish, antiepileptic effects were observed with all six AEDs. Among them, antiepileptic effects depending on dose were confirmed with valproate acid, gabapentin, ethosuximide, and tiagabine. Moreover, the 50% effective doses (ED50) of valproate acid and tiagabine were determined based on zebrafish EEG for the first time, indicating that the quantitative inter-species comparison of the AED efficacy is possible between zebrafish and mammals such as rodents. Significance: The results show that zebrafish can be used to effectively and quantitatively evaluate the efficacy of AEDs based on EEG, the same method to evaluate antiepileptic effects in mammals, suggesting that the proposed method can contribute in reducing the cost and duration of search for AEDs and thus accelerate the drug development cycles.

Protective Effects of Orexin A in a Murine Model of Cisplatin-Induced Acute Kidney Injury.

Cisplatin is a chemotherapeutic agent widely used in the treatment of various cancers, but its application is often limited due to complications such as acute kidney injury (AKI). Orexins are hypothalamic neuropeptides that modulate the sleep-wake cycle, neuroendocrine function, and the autonomic nervous system. Emerging evidence suggests that orexin A (OXA) has anti-inflammatory and neuroprotective effects in animal models of neuroinflammatory diseases of the central nervous system. However, the effect of OXA on kidney diseases has not been examined. Here, we investigated whether OXA has a protective effect in a murine model of cisplatin-induced AKI. Intraperitoneal administration of OXA ameliorated renal dysfunction, and histological abnormalities in mice injected with cisplatin. OXA inhibited cisplatin-induced oxidative stress through the modulation of prooxidant and antioxidant enzymes. This peptide reduced apoptotic cell death by inhibiting the p53-mediated pathway in mice injected with cisplatin. OXA also alleviated cisplatin-induced cytokine production and macrophage infiltration into injured kidneys. Taken together, these results showed that OXA ameliorates cisplatin-induced AKI via antioxidant, anti-apoptotic, and anti-inflammatory actions. This peptide could be a potential therapeutic agent for cisplatin-induced AKI.

MSeg-Net: A Melanoma Mole Segmentation Network Using CornerNet and Fuzzy K-Means Clustering.

Melanoma is a dangerous form of skin cancer that results in the demise of patients at the developed stage. Researchers have attempted to develop automated systems for the timely recognition of this deadly disease. However, reliable and precise identification of melanoma moles is a tedious and complex activity as there exist huge differences in the mass, structure, and color of the skin lesions. Additionally, the incidence of noise, blurring, and chrominance changes in the suspected images further enhance the complexity of the detection procedure. In the proposed work, we try to overcome the limitations of the existing work by presenting a deep learning (DL) model. Descriptively, after accomplishing the preprocessing task, we have utilized an object detection approach named CornerNet model to detect melanoma lesions. Then the localized moles are passed as input to the fuzzy K-means (FLM) clustering approach to perform the segmentation task. To assess the segmentation power of the proposed approach, two standard databases named ISIC-2017 and ISIC-2018 are employed. Extensive experimentation has been conducted to demonstrate the robustness of the proposed approach through both numeric and pictorial results. The proposed approach is capable of detecting and segmenting the moles of arbitrary shapes and orientations. Furthermore, the presented work can tackle the presence of noise, blurring, and brightness variations as well. We have attained the segmentation accuracy values of 99.32% and 99.63% over the ISIC-2017 and ISIC-2018 databases correspondingly which clearly depicts the effectiveness of our model for the melanoma mole segmentation.

Reaction-Based Scalable Inorganic Patterning on Rigid and Soft Substrates for Photovoltaic Roofs with Minimal Optical Loss and Sustainable Sunlight-Driven-Cleaning Windows.

Recently developed fabrication methods for inorganic patterns (such as laser printing and optical lithography) can avoid some patterning processes conducted by conventional etching and lithography (such as substrate etching and modulation) and are thereby useful for applications in which the substrates and materials must not be damaged during patterning. Simultaneously, it is also necessary to develop facile and economical methods producing inorganic patterns on various substrates without requiring a special apparatus while attaining the above-mentioned advantages. The present study proposes a reaction-based method for fabricating inorganic patterns by immersing substrates coated with a colloidal nanosheet into an aqueous solution containing inorganic precursors. Silica and TiO2 patterns spontaneously developed during the conversion of each inorganic precursor. These patterns were successful on rigid and flexible substrates. We fabricated these patterns on a wafer-sized silicon and large flexible poly(ethylene terephthalate) film, suggesting the scalability. We fabricated a biomimetic pattern on both sides of a glass window, as a photovoltaic roof, for minimal optical losses to maximally present photovoltaic effects of a solar cell. The TiO2 pattern on glass window exhibits sustainable sunlight-driven-cleaning activity for contaminants. The method could provide a platform for economical high-performance inorganic patterns for energy, environmental, electronics, and other areas.

Taurine Supplementation Inhibits the Expression of Atrogin-1 and MURF-1, Protein Degradation Marker Genes, in Skeletal Muscle of C26-Induced Cachexia Mouse Model.

This study was designed to investigate the therapeutic effects of taurine in attenuating muscle atrophy. C26 carcinoma cells were cultured and injected into the scapulae of Balb/c mice with 1 × 106 cells. Taurine (200 µl suspension) was orally administered at the concentration of 200 mg/kg of body weight for 2 weeks. Femur muscle tissue, spleen, and gonadal fat tissue were collected and weighed. Muscle tissue was stained by H&E for histopathological analysis. The transcriptional expression of atrogin-1 and MuRF-1 gene was checked by real-time PCR. C26 cells, which induced tumor growth, caused a loss in muscle mass and gonadal fat tissue mass. Simultaneously, there was an increase in spleen and tumor tissue mass. In contrast, taurine supplementation showed a downregulatory effect on the transcriptional expression profile of muscle degradative factors atrogin-1 and MuRF-1. Our findings suggest that taurine has the potential to inhibit muscle atrophy and can be developed as a safe treatment option against muscle loss in sarcopenia patients.

Kahweol Protects against Acetaminophen-Induced Hepatotoxicity in Mice through Inhibiting Oxidative Stress, Hepatocyte Death, and Inflammation.

Acetaminophen (APAP) can cause acute liver failure, but treatment options are still limited. Kahweol is the main diterpene compound of coffee and possesses antioxidant and anti-inflammatory properties. Emerging evidence suggests that this natural diterpene exerts favorable effects on several inflammatory diseases. However, the action of kahweol on APAP toxicity has not been addressed. The purpose of this study was to explore whether kahweol has a protective activity against APAP-induced hepatotoxicity and to investigate the mechanism. Administration of kahweol reduced serum levels of liver injury indicators and ameliorated histological abnormalities in APAP-treated mice. Kahweol inhibited lipid peroxidation and nucleic acid oxidation with restoration of glutathione content and stimulation of nuclear factor erythroid-2-related factor 2-dependent cellular defense system. Hepatocyte death was also decreased by kahweol, which was associated with inhibition of endoplasmic reticulum (ER) stress. Moreover, kahweol reduced hepatic levels of inflammatory mediators, inhibited nuclear factor-κB activation, and attenuated infiltration of neutrophils and macrophages. These findings suggest that kahweol has a protective activity against APAP-induced liver injury and this effect is related to the suppression of oxidative stress, hepatocyte death, ER stress, and inflammation.

Genomic evidence of SARS-CoV-2 reinfection in the Republic of Korea.

As the coronavirus disease 2019 (COVID-19) pandemic continues, reinfection is likely to become increasingly common. However, confirming COVID-19 reinfection is difficult because it requires whole-genome sequencing of both infections to identify the degrees of genetic differences. Since the first reported case of reinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Republic of Korea in April 2020, four additional cases were classified as suspected reinfection cases. We performed whole-genome sequencing of viral RNA extracted from swabs obtained at the initial infection and reinfection stages of these four suspected cases. The interval between initial infection and reinfection of all four suspected cases was more than 3 months. All four patients were young (10-29 years), and they displayed mild symptoms or were asymptomatic during the initial infection and reinfection episodes. The analysis of genome sequences combined with the epidemiological results revealed that only two of the four cases were confirmed as reinfection, and both were reinfected with the Epsilon variant. Due to the prolonged COVID-19 pandemic, the possibility of reinfections with SARS-CoV-2 variants is increasing, as reported in our study. Therefore, continuous monitoring of cases is necessary.

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

Effect of Process Control Parameters on the Filtration Performance of PAN-CTAB Nanofiber/Nanonet Web Combined with Meltblown Nonwoven.

Nanofibers have potential applications as filters for particles with diameters <10 µm owing to their large specific surface area, macropores, and controllable geometry or diameter. The filtration efficiency can be increased by creating nanonets (<50 nm) whose diameter is smaller than that of nanofibers. This study investigates the effect of process conditions on the generation of nanonet structures from a polyacrylonitrile (PAN) solution containing cation surfactants; in addition, the filtration performance is analyzed. The applied electrospinning voltage and the electrostatic treatment of meltblown polypropylene (used as a substrate) are the most influential process parameters of nanonet formation. Electrospun polyacrylonitrile-cetylmethylammonium bromide (PAN-CTAB) showed a nanofiber/nanonet structure and improved thermal and mechanical properties compared with those of the electrospun PAN. The pore size distribution and filter efficiency of the PAN nanofiber web and PAN-CTAB nanofiber/nanonet web with meltblown were measured. The resulting PAN-CTAB nanofiber/nanonet air filter showed a high filtration efficiency of 99% and a low pressure drop of 7.7 mmH2O at an air flow rate of 80 L/min. The process control methods for the nanonet structures studied herein provide a new approach for developing functional materials for air-filtration applications.

Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation.

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In mice fed a HFD and orally administered AzA, GLP-1 plasma levels were elevated in mice. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.

Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice.

Hepatocyte apoptosis and inflammation play important roles in cholestatic liver diseases. Bee venom-derived secretory phospholipase A2 (bvPLA2) has been shown to ameliorate various inflammatory diseases. However, whether bvPLA2 has a therapeutic effect against cholestatic liver disease has not been evaluated. Therefore, we investigated the effects of bvPLA2 on cholestatic liver injury and fibrosis in a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding. The administration of bvPLA2 ameliorated liver damage, cholestasis, and fibrosis in DDC diet-fed mice, as assessed by serum biochemical tests and histological examinations. In addition, bvPLA2 reduced myofibroblast accumulation, concomitant with suppression of transforming growth factor-ß signaling cascade. The administration of bvPLA2 inhibited hepatocyte apoptosis in DDC diet-fed mice as represented by a reduction in the number of cells stained with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and suppression of caspase-3 activation. Moreover, bvPLA2 reduced cytokine production along with the inhibition of the nuclear factor kappa-B pathway. The number of regulatory T-cells was increased by bvPLA2, while the number of other immune cells, including neutrophils, macrophages, and CD8+ T-cells, was decreased. Our data indicate that the administration of bvPLA2 ameliorates cholestatic liver injury and fibrosis by inhibiting hepatocyte apoptosis and inflammation.

Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model.

Cholestatic liver diseases can progress to end-stage liver disease and reduce patients' quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-ß pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.

Standardization of the pathologic diagnosis of appendiceal mucinous neoplasms.

Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the "Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm" to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.

The Role of Light and Circadian Clock in Regulation of Leaf Senescence.

Leaf senescence is an integrated response of the cells to develop age information and various environmental signals. Thus, some of the genes involved in the response to environmental changes are expected to regulate leaf senescence. Light acts not only as the primary source of energy for photosynthesis but also as an essential environmental cue that directly control plant growth and development including leaf senescence. The molecular mechanisms linking light signaling to leaf senescence have recently emerged, exploring the role of Phytochrome-Interacting Factors (PIFs) as a central player leading to diverse senescence responses, senescence-promoting gene regulatory networks (GRNs) involving PIFs, and structural features of transcription modules in GRNs. The circadian clock is an endogenous time-keeping system for the adaptation of organisms to changing environmental signals and coordinates developmental events throughout the life of the plant. Circadian rhythms can be reset by environmental signals, such as light-dark or temperature cycles, to match the environmental cycle. Research advances have led to the discovery of the role of core clock components as senescence regulators and their underlying signaling pathways, as well as the age-dependent shortening of the circadian clock period. These discoveries highlight the close relationship between the circadian system and leaf senescence. Key issues remain to be elucidated, including the effect of light on leaf senescence in relation to the circadian clock, and the identification of key molecules linking aging, light, and the circadian clock, and integration mechanisms of various senescence-affecting signals at the multi-regulation levels in dynamics point of view.