Leonurus japonicus Houtt. Modulates Neuronal Apoptosis in Intracerebral Hemorrhage: Insights from Network Pharmacology and Molecular Docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique,molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Polyethylene microplastics induced inflammation via the miR-21/IRAK4/NF-κB axis resulting to endoplasmic reticulum stress and apoptosis in muscle of carp.

As a widespread environmental pollutant, microplastics pose a great threat to the tissues and organs of aquatic animals. The carp's muscles are necessary for movement and survival. However, the mechanism of injury of polyethylene microplastics (PE-MPs) to carp muscle remains unclear. Therefore, in this study, PE-MPs with the diameter of 8 µm and the concentration of 1000 ng/L were used to feed carp for 21 days, and polyethylene microplastic treatment groups was established. The results showed that PE-MPs could cause structural abnormalities and disarrangement of muscle fibers, and aggravate oxidative stress in muscles. Exposure to PE-MPs reduced microRNA (miR-21) in muscle tissue, negatively regulated Interleukin-1 Receptor Associated Kinase 4 (IRAK4), activated Nuclear Factor Kappa-B (NF-κB) pathway, induced inflammation, and led to endoplasmic reticulum stress and apoptosis. The present study provides different targets for the prevention of muscle injury induced by polyethylene microplastics.

Subtractionless compressed-sensing-accelerated whole-body MR angiography using two-point Dixon fat suppression with single-pass half-reduced contrast dose: feasibility study and initial experience.

PURPOSE: To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). MATERIALS AND METHODS: This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. RESULTS: The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P < 0.001). In total, 1776 and 1406 arterial segments in the CS-WBMRA and conventional-WBMRA group were evaluated. Qualitative image scores for 7 (of 15) vessel segments in the CS-WMBRA group had statistically significantly increased values compared to those of the conventional-WBMRA groups (P < 0.05). Scores from the other 8 segments showed similar image quality (P > 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P < 0.001), while overall apparent CNRs were not significantly different in these two groups (CS vs conventional: 107.13 ± 72.323 vs 161.24 ± 118.64; P > 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and < 30 s for the conventional WBMRA group, respectively. The contrast agent dose used in the CS-WBMRA protocol was reduced by half compared to conventional-WBMRA protocol (18.7 ± 3.5 ml vs 37.2 ± 5.4 ml, P = 0.008). CONCLUSION: The CS-WBMRA protocol provides excellent image quality and sufficient diagnostic accuracy for whole-body arterial disease, with relatively faster workflow and half-dose reduction of contrast agent, which has greater potential in clinical practice compared with conventional-WBMRA.

Strongly fluorescent conjugated polymer nanoparticles in aqueous colloidal solution for universal, efficient and effective development of sebaceous and blood fingerprints.

Taking the same developing strategy for different types of latent fingerprints is helpful in improving the efficiency of criminal investigation. Here we advanced a new strategy based on amino-functionalized poly(p-phenylenevinylene) nanoparticles (PPV-brPEI NPs) in aqueous colloidal solution as the developing reagent. The desirable amino functionality and strong emission of NPs were simultaneously realized by adding branched polyethyleneimine (brPEI) during the process of thermal elimination of the PPV polymer precursor. The NPs were demonstrated to have negligible effects on the extraction of biological information from DNA. Using the PPV-brPEI NPs-soaked cotton pad, both latent sebaceous fingerprints (LSFPs) and latent blood fingerprints (LBFPs) can be effectively developed on different nonporous substrates. This strategy was highly sensitive and effective for aged, contaminated and moldy fingerprints. Additionally, the developed fingerprints could tolerate humidity environment and the alcohol atmosphere. The mechanism investigation suggests that interaction between PPV-brPEI NPs and sebum ingredients contributes to the development of LSFPs and interaction between PPV-brPEI NPs and proteins in blood contributes to the development of LBFPs, but the former is not as stable as the latter. This work provides a simple, environment/operator-friendly strategy for efficient fingerprint development, which is very promising for practical criminal investigations.

Arabidopsis Sec14 proteins (SFH5 and SFH7) mediate interorganelle transport of phosphatidic acid and regulate chloroplast development.

Lipids establish the specialized thylakoid membrane of chloroplast in eukaryotic photosynthetic organisms, while the molecular basis of lipid transfer from other organelles to chloroplast remains further elucidation. Here we revealed the structural basis of Arabidopsis Sec14 homology proteins AtSFH5 and AtSFH7 in transferring phosphatidic acid (PA) from endoplasmic reticulum (ER) to chloroplast, and whose function in regulating the lipid composition of chloroplast and thylakoid development. AtSFH5 and AtSFH7 localize at both ER and chloroplast, whose deficiency resulted in an abnormal chloroplast structure and a decreased thickness of stacked thylakoid membranes. We demonstrated that AtSFH5, but not yeast and human Sec14 proteins, could specifically recognize and transfer PA in vitro. Crystal structures of the AtSFH5-Sec14 domain in complex with L-α-phosphatidic acid (L-α-PA) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) revealed that two PA ligands nestled in the central cavity with different configurations, elucidating the specific binding mode of PA to AtSFH5, different from the reported phosphatidylethanolamine (PE)/phosphatidylcholine (PC)/phosphatidylinositol (PI) binding modes. Quantitative lipidomic analysis of chloroplast lipids showed that PA and monogalactosyldiacylglycerol (MGDG), particularly the C18 fatty acids at sn-2 position in MGDG were significantly decreased, indicating a disrupted ER-to-plastid (chloroplast) lipid transfer, under deficiency of AtSFH5 and AtSFH7. Our studies identified the role and elucidated the structural basis of plant SFH proteins in transferring PA between organelles, and suggested a model for ER-chloroplast interorganelle phospholipid transport from inherent ER to chloroplast derived from endosymbiosis of a cyanobacteriumproviding a mechanism involved in the adaptive evolution of cellular plastids.

Sleep disorder as a clinical risk factor of major depression: associated with cognitive impairment.

BACKGROUND: This research aims explored the sleep disorder (SD) role in major depressive disorder (MDD), and the SD influencing their cognition. METHODS: 372 MDD patients and 457 healthy controls (HCs) were enrolled. RESULTS: Patients increased a 38.88 times SD risk compared with HCs. In patients, visuospatial/constructional score was lower in SD than non-SD, and PSQI score was negatively associated with visuospatial/constructional score of SD. In SD and non-SD, RBANS scores were lower in MDD than HCs, excepted for visuospatial/constructional in non-SD. CONCLUSION: The SD as a MDD risk factor, has more serious visuospatial/constructional impairment alleviated via improving sleep/depression in patients.

Crystal structure of the phosphorylated Arabidopsis MKK5 reveals activation mechanism of MAPK kinases.

The mitogen-activated protein kinase (MAPK) signaling pathways are highly conserved in eukaryotes, regulating various cellular processes. The MAPK kinases (MKKs) are dual specificity kinases, serving as convergence and divergence points of the tripartite MAPK cascades. Here, we investigate the biochemical characteristics and three-dimensional structure of MKK5 in Arabidopsis (AtMKK5). The recombinant full-length AtMKK5 is phosphorylated and can activate its physiological substrate AtMPK6. There is a conserved kinase interacting motif (KIM) at the N-terminus of AtMKK5, indispensable for specific recognition of AtMPK6. The kinase domain of AtMKK5 adopts active conformation, of which the extended activation segment is stabilized by the phosphorylated Ser221 and Thr215 residues. In line with sequence divergence from other MKKs, the αD and αK helices are missing in AtMKK5, suggesting that the AtMKK5 may adopt distinct modes of upstream kinase/substrate binding. Our data shed lights on the molecular mechanisms of MKK activation and substrate recognition, which may help design specific inhibitors targeting human and plant MKKs.

Octreotide-based therapies effectively protect mice from acute and chronic gastritis.

Gastritis is a common inflammation of stomach with multiple pathogenesis. This study was designed to investigate the protective effects of oral octreotide (OCT) against ethanol-induced acute gastric injury and H. pylori-induced chronic gastritis via promoting gastric mucosa restoration, reducing gastric acid secretion and inflammation. Male C57BL/6J mice were randomly divided and treated with three doses of OCT (0.5, 2.5, 10 mg/kg) alone or combined respectively with 10 mg/kg omeprazole (OME), 0.2 g/L metronidazole (MTZ)/0.1 g/L clarithromycin (CLR) in drinking water. Oxidative stress analysis, bacterial load analysis, qPCR, gastric histopathology examinations were performed in our study. Ethanol-induced acute gastric ulcer was restored by OCT alone at doses of 2.5 mg/kg, or combined with OME as indicated by markedly reducing Gastrin, Il-6 and Il1b expression through induction of Muc5ac and Occludin, significantly improving hyperacidity and gastric bleeding. As well, OCT combined with MTZ/CLR restored the integrity of gastric mucosa damaged by H. pylori via elevating the expression of Muc5ac and somatostatin receptor 2, decreasing inflammation and increasing the number of chorionic or glands. Besides, OCT is more suitable for long-term medication in the treatment of chronic gastritis than OME. In conclusion, our results proved that the newly developed oral OCT-based therapies were more effective to reverse gastric mucosa damage and inflammation in ethanol and H. pylori infection-induced gastric injury, it is of great significance for supplementing new clinical regimens for the treatment of acute and chronic gastritis.

Tunable photosalient behaviours within coordination polymers via functional molecular prearrangements.

Four Cd(II)/diene coordination polymers (CPs) with similar 1D chain motifs exhibit different photosalient (PS) behaviours in response to UV light. The [2+2] photoreaction between the CC groups within these CPs results in diverse PS behaviours of their crystals with different CC pair arrangements. The interesting PS behaviours of these CPs can be applied in design and fabrication of advanced photoactuating materials.

ATPase inhibitory factor 1 protects the heart from acute myocardial ischemia/reperfusion injury through activating AMPK signaling pathway.

Rationale: Myocardial ischemia/reperfusion (I/R) injury is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction (AMI). The mitochondrial F1Fo-ATPase inhibitory factor 1 (IF1) blocks the reversal of the F1Fo-ATP synthase to prevent detrimental consumption of cellular ATP and associated demise. In the present study, we study the role and mechanism of IF1 in myocardial I/R injury. Methods: Mice were ligated the left anterior descending coronary artery to build the I/R model in vivo. Rat hearts were isolated and perfused with constant pressure according to Langendorff. Also, neonatal cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, cellular function, and cell viability was conducted and compared. Results: Our data revealed that IF1 is upregulated in hearts after I/R and cardiomyocytes with hypoxia/re-oxygenation (H/R). IF1 delivered with adenovirus and adeno-associated virus serotype 9 (AAV9) ameliorated cardiac dysfunction and pathological development induced by I/R ex vivo and in vivo. Mechanistically, IF1 stimulates glucose uptake and glycolysis activity and stimulates AMPK activation during in vivo basal and I/R and in vitro OGD/R conditions, and activation of AMPK by IF1 is responsible for its cardioprotective effects against H/R-induced injury. Conclusions: These results suggest that increased IF1 in the I/R heart confer cardioprotective effects via activating AMPK signaling. Therefore, IF1 can be used as a potential therapeutic target for the treatment of pathological ischemic injury and heart failure.

Taxonomic revision of Amolops chunganensis (Pope, 1929) (Amphibia: Anura) and description of a new species from southwestern China, with discussion on Amolops monticola group and assignment of species groups of the genus Amolops.

Amolops chunganensis is a species complex and reported widely from eastern, southern, and southwestern China. Based on molecular data of 19 populations of A. chunganensis sensu lato from China, including the population from Mt. Wuyi (type locality), we recognize A. chunganensis sensu stricto and provide an expanded description based on the topotypic specimens. Combining morphological and molecular data, we describe a new species, Amolops chaochin sp. nov., from southwestern China, which was previously identified as A. chunganensis. The new species is distinguished from all other species in the A. monticola group by: (1) moderate body size, SVL 35.3-39.2 mm in males (n=7), and 50.5-54.4 mm in females (n=7); (2) distinct tympanum, larger than half of eye diameter; (3) small tooth-like projection on anteromedial edge of mandible; (4) circummarginal groove on all fingers; (5) white tubercles on dorsal side of posterior body in both sexes; (6) distinct tubercles on dorsal thigh and white spinose tubercles on dorsal tibia in both sexes; (7) white tubercles on posterior region of tympanum in males; (8) toe webbing reaching disk by dermal fringe on inner side of toe II; (9) vomerine teeth present; (10) transverse bands on dorsal limbs; (11) external vocal sacs present in males. We further reviewed the assignment of Amolops groups, with an overall revision of membership and diagnosis of all species groups.

UCHL1 inhibition attenuates cardiac fibrosis via modulation of nuclear factor-κB signaling in fibroblasts.

The ubiquitin-proteasome system (UPS) plays an essential role in cellular homeostasis and myocardial function. Ubiquitin carboxy-terminal hydrolase 1 (UCHL1) is involved in cardiac remodeling, but its underlying mechanisms are largely unknown. Here, we observed that the UCHL1 was significantly up-regulated in angiotensin II-infused heart and primary cardiac fibroblast (CF). Systemic administration of the UCHL1 inhibitor LDN57444 significantly ameliorated cardiac fibrosis and improved cardiac function induced by angiotensin II. Also, LDN57444 inhibited CF cell proliferation as well as attenuated collagen I, and CTGF gene expression in the presence of Ang II. Mechanistically, UCHL1 promotes angiotensin II-induced fibrotic responses by way of activating nuclear factor kappa B (NF-κB) signaling. Moreover, suppression of the NF-κB pathway interfered with UCHL1 overexpression-mediated fibrotic responses. Besides, the chromatin immunoprecipitation assay demonstrated that NF-κB can bind to the UCHL1 promoter and trigger its transcription in cardiac fibroblasts. These findings suggest that UCHL1 positively regulates cardiac fibrosis by modulating NF-κB signaling pathway and identify UCHL1 could be a new treatment strategy for cardiac fibrosis.

Optimal exercise parameters of tai chi for balance performance in older adults: A meta-analysis.

BACKGROUND: Tai chi is considered a safe and low-cost treatment for improving balance ability among an older population. However, there is no existing evidence on the optimal exercise parameters of tai chi for improving balance in older adults. OBJECTIVES: To investigate the optimal parameters of a tai chi intervention to improve balance performance of older adults. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: PubMed, Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Periodical and China Biology Medicine were searched from inception until November 30, 2020. PARTICIPANTS: Adults aged 60 years and over. MEASUREMENTS: Two reviewers independently extracted the data and assessed the quality of the included studies according to the Physiotherapy Evidence Database (PEDro) scale. Subgroup analyses and meta-regressions were conducted to elucidate the impact of tai chi training programs on balance measures. RESULTS: Twenty-six eligible RCTs were included in the meta-analysis. Pooled results showed that tai chi has moderate effects for improving proactive balance (weighted mean standardized mean differences [SMDwm ] = 0.61, 95% CI 0.33-0.89) and static steady-state balance (SMDwm  = 0.62, 95% CI 0.30-0.95) and small effects for improving dynamic steady-state balance (SMDwm  = 0.38, 95% CI 0.03-0.73) and balance test batteries (SMDwm  = 0.47, 95% CI 0.13-0.81) in adults over 60 years of age. The practice frequency could predict the effects of tai chi on static steady-state balance, and the 24-form simplified Yang style tai chi (45-60 min/session, more than four sessions per week and at least 8 weeks) was the most optimal. CONCLUSIONS: Tai chi is effective at improving the balance ability of adults over 60 years of age. A medium duration and high frequency of 24-form tai chi may be the optimal program for improving balance, but this evidence should be recommended with caution due to limitations of the methodology and small sample sizes.

Highly Stable, Nondestructive, and Simple Visualization of Latent Blood Fingerprints Based on Covalent Bonding Between the Fluorescent Conjugated Polymer and Proteins in Blood.

Latent blood fingerprints (LBFPs) can provide critical information of foul play and help identify the suspects at violent crime scenes. The current methods for LBFP visualization are still not satisfactory because of the low sensitivity or complicated protocol. This study demonstrates a simple and effective LBFP visualization strategy by integrating a new amphiphilic fluorescent amino-functionalized conjugated polymer with the cotton-pad developing protocol. LBFPs on various substrates are visualized by simply covering them with the polymer solution-soaked cotton pads. The images display clear fingerprint patterns, ridge details, and sweat pores, even on very challenging substrates such as painted wood and multicolored can. The gray value analysis confirms semiquantitatively the enhancement of the contrast between ridges and furrows. Even LBFPs with various contaminations or aged for more than 600 days are effectively developed and visualized. The developed fingerprint images show superior stability over long storage time and against solvent washing. Moreover, the polymer causes no degradation of DNAs in the blood, suggesting the possibility of further DNA profiling and identification after development. The mechanistic investigation suggests that the formation of positive or inverted images can be attributed to the synergistic effects from the affinity between polymer and blood, and the affinity betwen polymer and substrate, as well as the slight quenching of polymer fluorescence by blood. Furthermore, the covalent bonding between the protonated primary amino group and proteins in blood endows the stability of the developed fingerprints. The result rationalizes the molecular design of the fluorescent polymer and sheds new light on the future strategies to effective LBFP visualization in practical applications.

Hypoxia-inducible factor 2-alpha-dependent induction of IL-6 protects the heart from ischemia/reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) results in increased myocardial infarct size and leads to poor clinical outcomes. Hypoxia-inducible factor 2-alpha (HIF2α) exerts myocardial protective effects during MIRI through as yet unclear mechanisms. Here, we show that knockdown of HIF2α with cardiotropic recombinant adeno-associated virus serotype 9 (rAAV9) in mouse hearts significantly increased the infarct sizes during myocardial ischemia/reperfusion (MI/R). In addition, HIF2α transcriptionally regulated the expression of interleukin 6 (IL-6) in cardiomyocytes to elicit cardioprotection. Likewise, IL-6 deficiency aggravated MIRI, while treatment with recombinant IL-6 had cardioprotective effects and rescued the mice with HIF2α knockdown. Furthermore, IL-6 treatment significantly activated the PI3K/Akt and STAT3 signaling pathways in the myocardium during MI/R, and the specific inhibitors wortmannin (specific phosphoinositide 3-kinase inhibitor) and Stattic (specific STAT3 inhibitor) substantially abolished HIF2α/IL-6-induced cardioprotection. These studies suggest that HIF2α transcription regulates the expression of IL-6 in cardiomyocytes and plays a protective role during MI/R.

Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure.

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Ac-DMPD-CMK and Ac-DMLD-CMK could directly bind to the catalytic domains of caspase-3 and specifically inhibit caspase-3 activity, exhibiting a lower IC50 than that of Z-DEVD-FMK. Functionally, Ac-DMPD/DMLD-CMK substantially inhibited both GSDME and PARP cleavage by caspase-3, preventing apoptotic and pyroptotic events in hepatocytes and macrophages. Furthermore, in a mouse model of bile duct ligation that mimics intrahepatic cholestasis-related acute hepatic failure, Ac-DMPD/DMLD-CMK significantly alleviated liver injury. Together, this study not only identified two specific inhibitors of caspase-3 for investigating PCD but also, more importantly, shed light on novel lead compounds for treating liver failure and organ dysfunctions caused by PCD.

Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum.

Plasmodium species, the causative agent of malaria, rely on glucose for energy supply during blood stage. Inhibition of glucose uptake thus represents a potential strategy for the development of antimalarial drugs. Here, we present the crystal structures of PfHT1, the sole hexose transporter in the genome of Plasmodium species, at resolutions of 2.6 Å in complex with D-glucose and 3.7 Å with a moderately selective inhibitor, C3361. Although both structures exhibit occluded conformations, binding of C3361 induces marked rearrangements that result in an additional pocket. This inhibitor-binding-induced pocket presents an opportunity for the rational design of PfHT1-specific inhibitors. Among our designed C3361 derivatives, several exhibited improved inhibition of PfHT1 and cellular potency against P. falciparum, with excellent selectivity to human GLUT1. These findings serve as a proof of concept for the development of the next-generation antimalarial chemotherapeutics by simultaneously targeting the orthosteric and allosteric sites of PfHT1.

Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration.

Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration in Caenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1-dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

The omics based study for the role of superoxide dismutase 2 (SOD2) in keratinocytes: RNA sequencing, antibody-chip array and bioinformatics approaches.

In this study, we aimed to identify critical factors associated with superoxide dismutase 2 (SOD2) in human keratinocytes through gene and protein expression profiling approaches. After recombinant SOD2 was exogenously added to culture media, we conducted serial OMICS studies, which included RNA sequencing analysis, integrated antibody-chip arrays, and the implementation of bioinformatics algorithms, in order to reveal genes and proteins that are possibly associated with SOD2 in keratinocytes. These approaches identified several novel genes and proteins in keratinocytes that are associated with exogenous SOD2. These novel genes included DCT, which was up-regulated, and CD38, GPR151, HCK, KIT, and AFP, which were down-regulated. Among them, CD38 and KIT were also predicted as hub proteins in PPI mappings. By integrating the datasets obtained from these complementary high-throughput OMICS studies and utilizing the strengths of each method, we obtained new insights into the functional role of externally added SOD2 in skin cells and into several critical genes that are thought to play important roles in SOD2-associated skin function. The approach used here could help contribute to our clinical understanding of SOD2-associated applications and may be broadly applicable to a wider range of diseases. AbbreviationsSOD2superoxide dismutase 2DAVIDthe database for annotation, visualization and integrated discoveryKEGGKyoto Encyclopedia of Genes and GenomesPPIprotein-protein interactionsHTSHigh-throughput screeningCommunicated by Ramaswamy H. Sarma.