Stearoyl-CoA desaturase 1 inhibition induces ER stress-mediated apoptosis in ovarian cancer cells.

Ovarian cancer is a leading cause of death among gynecologic tumors, often detected at advanced stages. Metabolic reprogramming and increased lipid biosynthesis are key factors driving cancer cell growth. Stearoyl-CoA desaturase 1 (SCD1) is a crucial enzyme involved in de novo lipid synthesis, producing mono-unsaturated fatty acids (MUFAs). Here, we aimed to investigate the expression and significance of SCD1 in epithelial ovarian cancer (EOC). Comparative analysis of normal ovarian surface epithelial (NOSE) tissues and cell lines revealed elevated SCD1 expression in EOC tissues and cells. Inhibition of SCD1 significantly reduced the proliferation of EOC cells and patient-derived organoids and induced apoptotic cell death. Interestingly, SCD1 inhibition did not affect the viability of non-cancer cells, indicating selective cytotoxicity against EOC cells. SCD1 inhibition on EOC cells induced endoplasmic reticulum (ER) stress by activating the unfolded protein response (UPR) sensors and resulted in apoptosis. The addition of exogenous oleic acid, a product of SCD1, rescued EOC cells from ER stress-mediated apoptosis induced by SCD1 inhibition, underscoring the importance of lipid desaturation for cancer cell survival. Taken together, our findings suggest that the inhibition of SCD1 is a promising biomarker as well as a novel therapeutic target for ovarian cancer by regulating ER stress and inducing cancer cell apoptosis.

Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.

The BMAL1/HIF2A heterodimer modulates circadian variations of myocardial injury.

Acute myocardial infarction stands as a prominent cause of morbidity and mortality worldwide1-6. Clinical studies have demonstrated that the severity of cardiac injury following myocardial infarction exhibits a circadian pattern, with larger infarct sizes and poorer outcomes in patients experiencing morning onset myocardial infarctions7-14. However, the molecular mechanisms that govern circadian variations of myocardial injury remain unclear. Here, we show that BMAL114-20, a core circadian transcription factor, orchestrates diurnal variability in myocardial injury. Unexpectedly, BMAL1 modulates circadian-dependent cardiac injury by forming a transcriptionally active heterodimer with a non-canonical partner, hypoxia-inducible factor 2 alpha (HIF2A)6,21-23, in a diurnal manner. Substantiating this finding, we determined the cryo-EM structure of the BMAL1/HIF2A/DNA complex, revealing a previously unknown capacity for structural rearrangement within BMAL1, which enables the crosstalk between circadian rhythms and hypoxia signaling. Furthermore, we identified amphiregulin (AREG) as a rhythmic transcriptional target of the BMAL1/HIF2A heterodimer, critical for regulating circadian variations of myocardial injury. Finally, pharmacologically targeting the BMAL1/HIF2A-AREG pathway provides effective cardioprotection, with maximum efficacy when aligned with the pathway's circadian trough. Our findings not only uncover a novel mechanism governing the circadian variations of myocardial injury but also pave the way for innovative circadian-based treatment strategies, potentially shifting current treatment paradigms for myocardial infarction.

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer.

Obesity is recognized as a significant risk factor for ovarian cancer, with accumulating evidence highlighting its impact on disease progression and chemoresistance. This review synthesizes current research elucidating the link between obesity-induced lysosomal dysfunction and ovarian cancer chemoresistance. Epidemiological studies consistently demonstrate a positive correlation between body mass index (BMI) and ovarian cancer risk, attributed in part to the predilection of epithelial ovarian cancer cells for adipose tissue, particularly the omentum. Adipokines released from the omentum contribute to cancer-associated characteristics, including energy supply to cancer cells. Moreover, obesity-induced alterations in lysosomal function have been implicated in systemic inflammation and lipid metabolism dysregulation, further exacerbating cancer progression. Lysosomes play a crucial role in drug resistance, as evidenced by studies demonstrating their involvement in mediating resistance to chemotherapy in ovarian cancer cells. Recent findings suggest that pharmacological inhibition of lysosomal calcium channels sensitizes drug-resistant ovarian cancer cells to cisplatin treatment, highlighting the therapeutic potential of targeting lysosomal dysfunction in obesity-related chemoresistance. This review underscores the importance of understanding the multifaceted roles of lysosomes in obesity-related drug resistance and their implications for the development of targeted therapeutic interventions in ovarian cancer management.

Modulation of Cisplatin Sensitivity through TRPML1-Mediated Lysosomal Exocytosis in Ovarian Cancer Cells: A Comprehensive Metabolomic Approach.

BACKGROUND: The lysosome has emerged as a promising target for overcoming chemoresistance, owing to its role in facilitating the lysosomal sequestration of drugs. The lysosomal calcium channel TRPML1 not only influences lysosomal biogenesis but also coordinates both endocytosis and exocytosis. This study explored the modulation of cisplatin sensitivity by regulating TRPML1-mediated lysosomal exocytosis and identified the metabolomic profile altered by TRPML1 inhibition. METHODS: We used four types of ovarian cancer cells: two cancer cell lines (OVCAR8 and TOV21G) and two patient-derived ovarian cancer cells. Metabolomic analyses were conducted to identify altered metabolites by TRPML1 inhibition. RESULTS: Lysosomal exocytosis in response to cisplatin was observed in resistant cancer cells, whereas the phenomenon was absent in sensitive cancer cells. Through the pharmacological intervention of TRPML1, lysosomal exocytosis was interrupted, leading to the sensitization of resistant cancer cells to cisplatin treatment. To assess the impact of lysosomal exocytosis on chemoresistance, we conducted an untargeted metabolomic analysis on cisplatin-resistant ovarian cancer cells with TRPML1 inhibition. Among the 1446 differentially identified metabolites, we focused on 84 significant metabolites. Metabolite set analysis revealed their involvement in diverse pathways. CONCLUSIONS: These findings collectively have the potential to enhance our understanding of the interplay between lysosomal exocytosis and chemoresistance, providing valuable insights for the development of innovative therapeutic strategies.

Approximate Bayesian computation and ecological niche models elucidate the demographic history and current fragmented population distribution of a Korean endemic shrub.

Climatic fluctuations and geological events since the LGM are believed to have significantly impacted the population size, distribution, and mobility of many species that we observe today. In this paper, we determined the processes driving the phylogeographic structure of the Korean endemic white forsythia by combining the use of genome-wide SNPs and predicting paleoclimatic habitats during the LGM (21 kya), Early Holocene (10 kya), Mid-Holocene (6 kya), and Late Holocene (3 kya). Using a maximum of 1897 SNPs retrieved from 124 samples across nine wild populations, five environmental predictors, and the species' natural occurrence records, we aimed to infer the species' demographic history and reconstruct its possible paleodistributions with the use of approximate Bayesian computation and ecological niche models, respectively. Under this integrated framework, we found strong evidence for patterns of range shift and expansion, and population divergence events from the onset of the Holocene, resulting in the formation of its five distinct genetic units. The most highly supported model inferred that after the split of an ancestral population into the southern group and a larger central metapopulation lineage, the latter gave rise to the eastern and northern clusters, before finally dividing into two sub-central groups. While the use of molecular data allowed us to identify and refine the (phylo)genetic relationships of the species' lineages and populations, the use of ecological data helped us infer a past LGM refugium and the directions of post-glacial range dynamics. The time frames of these demographic events were shown to be congruent with climatic and geological events that affected the central Korean Peninsula during these periods. These findings gave us a better understanding of the consequences of past spatiotemporal factors that may have resulted in the current fragmented population distribution of this endangered plant.

Yeast Hydrolysate Inhibits Lipid Accumulation via Regulation of Lipid Accumulation-Related Genes in a Drosophila Model of High-Sugar Diet-Induced Obesity.

The increasing frequency of processed food consumption has led to the higher ingestion of sugar, increasing the risk of chronic diseases, such as obesity. Yeast hydrolysates (YHs) inhibit body fat accumulation. However, the action mechanism of YH in relation to high-sugar diet-induced obesity is still unclear. Therefore, this study aimed to evaluate the biological effects of YH on lipid accumulation and verify behavioral changes and carbohydrate metabolic gene regulation in high-sugar diet-fed fruit flies. Adult male flies (Drosophila melanogaster; 2-5 days old) were exposed to 20% sucrose for obesity induction. In high-sugar-fed Drosophila, the effect of YH was compared with that of yeast extract. The effects of YH on body conditions and lipid droplet size were quantified and analyzed. Behavioral factors were evaluated by analyzing circadian rhythm patterns and neurotransmitter content, and a molecular approach was used to analyze the expression of metabolism-related genes. Dietary supplementation with YH did not reduce total sugar content, but significantly decreased the triglyceride (TG) levels in Drosophila. A behavioral analysis showed that the total number of night-time activities increased significantly with YH treatment in a dose-dependent manner. In addition, YH effectively regulated the gene expression of insulin-like peptides related to carbohydrate metabolism as well as genes related to lipogenesis. The TG content was significantly reduced at a YH concentration of 0.5%, confirming that the active compound in YH effectively suppresses fat accumulation. These findings support that YH is a potential anti-obesity food material via regulating carbohydrate metabolism in Drosophila.

Enhanced recellularization by using albumin coating with roller bottle cell culture.

Introduction: The decellularization and recellularization is a promising approach for tissue engineering and regenerative medicine. However, the decellularization process depletes important components like glycosaminoglycans (GAGs), affecting cell attachment and causing immunogenicity. Studies have explored various surface modification strategies to enhance recellularization. Methods: To optimize the decellularization method, we employed whole kidney perfusion and slice kidney immersion/agitation techniques. The decellularized extracellular matrix (dECM) was then analyzed using hematoxylin and eosin (H&E) staining, scanning electron microscope (SEM), and DNA quantification. To enhance cell proliferation efficiency, albumin coating and rotating culture were applied. Also, we evaluated in vitro blood clot formation on the albumin-coated dECM by immersing it in blood. Results: After decellularization, the unique structures of the kidney were preserved whether cellular components were removed. Subsequently, we utilized albumin coating and rotating culture for recellularization, and observed that albumin-coated dECM not only promoted high cell proliferation rates but also prevented blood clot formation. Conclusion: The albumin-coated dECM promoted cell proliferation and reduced blood clot formation in vitro. Also, dynamic culture condition using rotating culture allowed for improved cellular penetration into the dECM, leading to a conductive environment for enhanced tissue infiltration. This new approach suggests that the combined utilization of albumin coating and rotating culture conditions can improve the efficiency of recellularization.

The complete chloroplast genome sequences of six Hylotelephium species: Comparative genomic analysis and phylogenetic relationships.

To evaluate the phylogenetic relationships between Hylotelephium and Orostachys, and to provide important information for further studies, we analyzed the complete chloroplast genomes of six Hylotelephium species and compared the sequences to those of published chloroplast genomes of congeneric species and species of the closely related genus, Orostachys. The total chloroplast genome length of nineteen species, including the six Hylotelephium species analyzed in this study and the thirteen Hylotelephium and Orostachys species analyzed in previous studies, ranged from 150,369 bp (O. minuta) to 151,739 bp (H. spectabile). Their overall GC contents were almost identical (37.7-37.8%). The chloroplast genomes of the nineteen species contained 113 unique genes comprising 79 protein-coding genes (PCGs), 30 transfer RNA genes (tRNAs), and four ribosomal RNA genes (rRNAs). Among the annotated genes, fourteen genes contained one intron, and two genes contained two introns. The chloroplast genomes of the nineteen Hylotelephium and Orostachys species had identical structures. Additionally, the large single copy (LSC), inverted repeat (IR), and small single copy (SSC) junction regions were conserved in the Hylotelephium and Orostachys species. The nucleotide diversity between the Hylotelephium chloroplast genomes was extremely low in all regions, and only one region showed a high Pi value (>0.03). In all nineteen chloroplast genomes, six regions had a high Pi value (>0.03). The phylogenetic analysis showed that the genus delimitation could not be clearly observed even in this study because Hylotelephium formed a paraphyly with subsect. Orostachys of the genus Orostachys. Additionally, the data supported the taxonomic position of Sedum taqeutii, which was treated as a synonym for H. viridescens in previous studies, as an independent taxon.

Functional Analysis of Pheromone Biosynthesis Activating Neuropeptide Receptor Isoforms in Maruca vitrata.

Insect sex pheromones are volatile chemicals that induce mating behavior between conspecific individuals. In moths, sex pheromone biosynthesis is initiated when pheromone biosynthesis-activating neuropeptide (PBAN) synthesized in the suboesophageal ganglion binds to its receptor on the epithelial cell membrane of the pheromone gland. To investigate the function of PBAN receptor (PBANR), we identified two PBANR isoforms, MviPBANR-B and MviPBANR-C, in the pheromone glands of Maruca vitrata. These two genes belong to G protein-coupled receptors (GPCRs) and have differences in the C-terminus but share a 7-transmembrane region and GPCR family 1 signature. These isoforms were expressed in all developmental stages and adult tissues. MviPBANR-C had the highest expression level in pheromone glands among the examined tissues. Through in vitro heterologous expression in HeLa cell lines, only MviPBANR-C-transfected cells responded to MviPBAN (≥5 µM MviPBAN), inducing Ca2+ influx. Sex pheromone production and mating behavior were investigated using gas chromatography and a bioassay after MviPBANR-C suppression by RNA interference, which resulted in the major sex pheromone component, E10E12-16:Ald, being quantitatively reduced compared to the control, thereby decreasing the mating rate. Our findings indicate that MviPBANR-C is involved in the signal transduction of sex pheromone biosynthesis in M. vitrata and that the C-terminal tail plays an important role in its function.

Zinc oxide nanoparticles trigger autophagy-mediated cell death through activating lysosomal TRPML1 in normal kidney cells.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey's post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity.

Safety assessment of a three-dimensional-printed autologous omentum patch: An application on the kidneys as a new treatment approach.

Recently, the field of regenerative medicine has made great strides in the development of new treatments for various organ dysfunctions. One of the most promising new approaches is the use of three-dimensional (3D) printing and autologous tissues. In this study, we evaluated the safety of a 3D-printed autologous omentum patch to kidneys using large animals. A total of seven micropigs underwent transplantation of the 3D-printed autologous omentum patch. Twelve weeks after transplantation, the safety was evaluated by measuring body weight, blood, and the renal resistive index. In addition, biopsy samples were histologically analyzed. The results showed no surgical complications, renal functional hematological changes, or inflammatory responses. Therefore, this study provides important insights into direct therapy to kidneys with a 3D-printed patch made of autologous tissue. Furthermore, it has the potential for the development of new therapies for various organ dysfunction.

Isolation and Characterization of the Genes Involved in the Berberine Synthesis Pathway in Asian Blue Cohosh, Caulophyllum robustum.

Caulophyllum robustum, commonly named Asian blue cohosh, is a perennial herb in the family Berberidaceae. It has traditionally been used for folk medicine in China. We isolated berberine from the leaves, stem, roots, and fruits of C. robustum, and this is the first report on berberine in this species. Transcriptome analysis was conducted for the characterization of berberine biosynthesis genes in C. robustum, in which, all the genes for berberine biosynthesis were identified. From 40,094 transcripts, using gene ontology (GO) analysis, 26,750 transcripts were assigned their functions in the categories of biological process, molecular function, and cellular component. In the analysis of genes expressed in different tissues, the numbers of genes in the categories of intrinsic component of membrane and transferase activity were up-regulated in leaves versus stem. The berberine synthesis genes in C. robustum were characterized by phylogenetic analysis with corresponding genes from other berberine-producing species. The co-existence of genes from different plant families in the deepest branch subclade implies that the differentiation of berberine synthesis genes occurred early in the evolution of berberine-producing plants. Furthermore, the copy number increment of the berberine synthesis genes was detected at the species level.

Flexible Organic Photodetectors with Mechanically Robust Zinc Oxide Nanoparticle Thin Films.

Zinc oxide nanoparticle (ZnO-NP) thin films have been intensively used as electron transport layers (ETLs) in organic optoelectronic devices, but their moderate mechanical flexibility hinders their application to flexible electronic devices. This study reveals that the multivalent interaction between ZnO-NPs and multicharged conjugated electrolytes, such as diphenylfluorene pyridinium bromide derivative (DFPBr-6), can significantly improve the mechanical flexibility of ZnO-NP thin films. Intermixing ZnO-NPs and DFPBr-6 facilitates the coordination between bromide anions (from the DFPBr-6) and zinc cations on ZnO-NP surfaces, forming Zn2+-Br- bonds. Different from a conventional electrolyte (e.g., KBr), DFPBr-6 with six pyridinium ionic side chains holds the Br--chelated ZnO-NPs adjacent to DFP+ through Zn2+-Br--N+ bonds. Consequently, ZnO-NP:DFPBr-6 thin films exhibit improved mechanical flexibility with a critical bending radius as low as 1.5 mm under tensile bending conditions. Flexible organic photodetectors with ZnO-NP:DFPBr-6 thin films as ETLs demonstrate reliable device performances with high R (0.34 A/W) and D* (3.03 × 1012 Jones) even after 1000 times repetitive bending at a bending radius of 4.0 mm, whereas devices with ZnO-NP and ZnO-NP:KBr ETLs yield >85% reduction in R and D* under the same bending condition.

Genetic and demographic signatures accompanying the evolution of the selfing syndrome in Daphne kiusiana, an evergreen shrub.

BACKGROUND AND AIMS: The evolution of mating systems from outcrossing to self-fertilization is a common transition in flowering plants. This shift is often associated with the 'selfing syndrome', which is characterized by less visible flowers with functional changes to control outcrossing. In most cases, the evolutionary history and demographic dynamics underlying the evolution of the selfing syndrome remain poorly understood. METHODS: Here, we characterize differences in the demographic genetic consequences and associated floral-specific traits between two distinct geographical groups of a wild shrub, Daphne kiusiana, endemic to East Asia; plants in the eastern region (southeastern Korea and Kyushu, Japan) exhibit smaller and fewer flowers compared to those of plants in the western region (southwestern Korea). Genetic analyses were conducted using nuclear microsatellites and chloroplast DNA (multiplexed phylogenetic marker sequencing) datasets. KEY RESULTS: A high selfing rate with significantly increased homozygosity characterized the eastern lineage, associated with lower levels of visibility and herkogamy in the floral traits. The two lineages harboured independent phylogeographical histories. In contrast to the western lineage, the eastern lineage showed a gradual reduction in the effective population size with no signs of a severe bottleneck despite its extreme range contraction during the last glacial period. CONCLUSIONS: Our results suggest that the selfing-associated morphological changes in D. kiusiana are of relatively old origin (at least 100 000 years ago) and were driven by directional selection for efficient self-pollination. We provide evidence that the evolution of the selfing syndrome in D. kiusiana is not strongly associated with a severe population bottleneck.

The complete chloroplast genome sequences of eight Orostachys species: Comparative analysis and assessment of phylogenetic relationships.

We analyzed the complete chloroplast genomes of eight Orostachys species and compared the sequences to those of published chloroplast genomes of the congeneric and closely related genera, Meterostachys and Hylotelephium. The total chloroplast genome length of thirteen species, including the eight species analyzed in this study and the five species analyzed in previous studies, ranged from 149,860 (M. sikokianus) to 151,707 bp (H. verticillatum). The overall GC contents of the genomes were almost identical (37.6 to 37.8%). The thirteen chloroplast genomes each contained 113 unique genes comprising 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Among the annotated genes, sixteen genes contained one or two introns. Although the genome structures of all Orostachys and Hylotelephium species were identical, Meterostachys differed in structure due to a relatively large gene block (trnS-GCU-trnS-GGA) inversion. The nucleotide diversity among the subsect. Orostachys chloroplast genomes was extremely low in all regions, and among the subsect. Appendiculatae, genus Orostachys, and all thirteen chloroplast genomes showed high values of Pi (>0.03) in one, five, or three regions. The phylogenetic analysis showed that Orostachys formed polyphyly, and subsect. Orostachys and Appendiculatae were clustered with Hylotelephium and Meterostachys, respectively, supporting the conclusion that each subsection should be considered as an independent genus. Furthermore, the data supported the taxonomic position of O. margaritifolia and O. iwarenge f. magnus, which were treated as synonyms for O. iwarenge in a previous study, as independent taxa. Our results suggested that O. ramosa and O. japonica f. polycephala were individual variations of O. malacophylla and O. japonica, respectively. The exact taxonomic position of O. latielliptica and the phylogenetic relationship among the three species, O. chongsunensis, O. malacophylla and O. ramosa, should be a topic of future study.

The complete plastid genome sequence of Chloranthus fortunei (A. Gray) Solms-Laub. in Chloranthaceae.

Chloranthus fortunei (A. Gray) Solms-Laub. is a perennial herb in a basal angiosperm family Chloranthaceae. Here, we reported the complete plastid genome of C. fortunei using Illumina short-read data. The total genome size was 157,063 bp in length, containing 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. The gene content and order were consistent with previously reported Chloranthus plastid genomes. The overall GC content of the C. fortunei plastid genome was 39.0%. In the phylogenetic result, genus Chloranthus was monophyletic and divided into two subclades: C. japonicus+C. angustifolius+C. fortunei, and C. henryi+C. spicatus+C. erectus. Our phylogenetic result was consistent with previous phylogenetic studies, and was supported by a previously proposed infrageneric classification of the genus Chloranthus.

The complete chloroplast genome sequence of Orostachys minuta (Crassulaceae).

The chloroplast (cp) genome sequence is determined and analyzed for Orostachys minuta for the first time. The cp genome was 150,369 bp in length, containing a large single-copy (LSC) of 82,795 bp and a small single-copy (SSC) of 16,854 bp, which were separated by a pair of 25,360 bp inverted repeats (IRs). The overall G + C content of the O. minuta cp genome amounted to 37.7%. In total, 113 unique genes were annotated, consisting of 79 protein-coding genes (PCGs), 30 transfer RNAs (tRNAs), and four ribosomal RNAs (rRNAs). Among these genes, 18 contained one or two introns. A maximum-likelihood (ML) phylogenetic analysis based on 33 taxa showed that O. minuta formed a clade with O. japonica. This study will provide a baseline as well as valuable molecular phylogenomic information for various future studies to determine the taxonomic position and phylogenetic relationships of the genus Orostachys.

Three-Dimensional Bio-Printed Autologous Omentum Patch Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis.

Recent advances in the field of tissue engineering and regenerative medicine have contributed to the repair of damaged tissues and organs. Renal dysfunctions such as chronic kidney disease (CKD) are considered intractable owing to its cellular heterogeneity. In addition, the absence of definitive treatment options other than dialysis or kidney transplantation in advanced CKD. In this study, we investigated therapeutic effects of a three-dimensional (3D) bio-printed omentum patch as treatment source. Because omentum contains a lot of biological sources for immune regulation and tissue regeneration, it has been used in clinic for >100 years. By using autologous tissue as a bio-ink, the patch could minimize the immune response. The mechanically micronized omentum without any additives became small enough to print, but the original components could be preserved. Then, the 3D printed omentum patch was transplanted under renal subcapsular layer in unilateral ureteral obstruction (UUO) rat model. After 14 days of patch transplantation, the kidneys were analyzed through bulk RNA sequencing and histopathological staining. From the results, decreased tubular injury was observed in the omentum patch group. In addition, the omentum patch significantly altered biological process of gene ontology such as fibrosis-related gene and growth factors. RNA sequencing confirmed the antifibrotic effect by inhibiting fibrosis-inducing mechanisms within PI3K-AKT and JAK-STAT pathways. In conclusion, the omentum patch showed the effect of antitubular injury and antifibrosis on UUO kidneys. In particular, the omentum patch is expected to protect the organ from further degeneration and loss of function by inhibiting the progression of fibrosis. The omentum patch can be a novel therapeutic option for renal dysfunction. Impact statement Many studies and clinical trials are being conducted to develop new treatments for kidney disease. However, there are no newly developed renal replacement therapies. In this study, we developed a new treatment that can ameliorate renal interstitial fibrosis using three-dimensional (3D) bio-printed autologous omentum patch. The 3D printer enables precise patch printing, and the bio-ink made of autologous tissue minimizes the immune response after transplantation. The whole kidneys were analyzed by RNA sequencing and histopathological staining 14 days after transplantation. From the results, the omentum patch had the effect of relieving tubular injury in the injured state. Also, the omentum patch significantly altered biological process of gene ontology. In particular, genes related to fibrosis were observed to be downregulated by the omentum patch. RNA sequencing confirmed that the antifibrotic effect was owing to inducing mechanisms of PI3K-AKT and JAK-STAT pathways. The findings reported in this study represent a significant advancement in the application of 3D bio-printer to damaged organ treatments, especially fibrosis-related diseases.

Comparative Transcriptomics for Genes Related to Berberine and Berbamine Biosynthesis in Berberidaceae.

Berberine and berbamine are bioactive compounds of benzylisoquinoline alkaloids (BIAs) present in Berberis species. The contents of berbamine are 20 times higher than berberine in leaf tissues in three closely related species: Berberis koreana, B. thunbergii and B. amurensis. This is the first report on the quantification of berberine compared to the berbamine in the Berberis species. Comparative transcriptome analyses were carried out with mRNAs from the leaf tissues of the three-species. The comparison of the transcriptomes of B. thunbergii and B. amurensis to those of B. koreana, B. thunbergii showed a consistently higher number of differentially expressed genes than B. amurensis in KEGG and DEG analyses. All genes encoding enzymes involved in berberine synthesis were identified and their expressions were variable among the three species. There was a single copy of CYP80A/berbamunine synthase in B. koreana. Methyltransferases and cytochrome P450 mono-oxidases (CYPs) are key enzymes for BIA biosynthesis. The current report contains the copy numbers and other genomic characteristics of the methyltransferases and CYPs in Berberis species. Thus, the contents of the current research are valuable for molecular characterization for the medicinal utilization of the Berberis species.