Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry.

BACKGROUND: We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR. RESULTS: Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122-1.316), systolic blood pressure (OR 1.203, 95% CI 1.117-1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023-1.129) and triglyceride (OR 2.18, 95% CI 1.485-3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found. CONCLUSIONS: We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.

Gas exchange and chlorophyll fluorescence responses of Camellia sinensis grown under various cultivations in different seasons.

Sod culture (SC) and conventional agriculture (CA) represent two distinct field management approaches utilized in the cultivation of tea plants in Taiwan. In this study, we employed gas exchange and chlorophyll fluorescence techniques to assess the impact of SC and CA methods on the photosynthetic machinery of Camellia sinensis cv. TTES No.12 (Jhinhsuan) in response to variable light intensities across different seasons. In spring, at photosynthetic photon flux densities (PPFD) ranging from 800 to 2,000 µmol photon m-2 s-1, the net photosynthesis rate (Pn, 10.43 µmol CO2 m-2 s-1), stomatal conductance (Gs, 126.11 mmol H2O m-2 s-1), electron transport rate (ETR, 137.94), and ΔF/Fm' and Fv/Fm (50.37) values for plants grown using SC were comparatively higher than those cultivated under CA. Conversely, the non-photochemical quenching (NPQ) values for SC-grown plants were relatively lower (3.11) compared to those grown under CA at 800 to 2,000 PPFD in spring. Additionally, when tea plants were exposed to PPFD levels below 1,500 µmol photon m- 2 s- 1, there was a concurrent increase in Pn, Gs, ETR, and NPQ. These photosynthetic parameters are crucial for devising models that optimize cultivation practices across varying seasons and specific tillage requirements, and for predicting photosynthetic and respiratory responses of tea plants to seasonally or artificially altered light irradiances. The observed positive impacts of SC on maximum photosynthetic rate (Amax), Fv/Fm, Gs, water-use efficiency (WUE), and ETR suggest that SC is advantageous for enhancing the productivity of tea plants, thereby offering a more adaptable management model for tea gardens.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

A simple, organized web-based system improved the transfer efficiency and patient outcomes for endovascular thrombectomy in regional stroke network.

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

Lysophosphatidic Acid Receptor 3 Activation Is Involved in the Regulation of Ferroptosis.

Ferroptosis, a unique form of programmed cell death trigged by lipid peroxidation and iron accumulation, has been implicated in embryonic erythropoiesis and aging. Our previous research demonstrated that lysophosphatidic acid receptor 3 (LPA3) activation mitigated oxidative stress in progeria cells and accelerated the recovery of acute anemia in mice. Given that both processes involve iron metabolism, we hypothesized that LPA3 activation might mediate cellular ferroptosis. In this study, we used an LPA3 agonist, 1-Oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT), to activate LPA3 and examine its effects on the ferroptosis process. OMPT treatment elevated anti-ferroptosis gene protein expression, including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), heme oxygenase-1 (HO-1), and ferritin heavy chain (FTH1), in erastin-induced cells. Furthermore, OMPT reduced lipid peroxidation and intracellular ferrous iron accumulation, as evidenced by C11 BODIPY™ 581/591 Lipid Peroxidation Sensor and FerroOrange staining. These observations were validated by applying LPAR3 siRNA in the experiments mentioned above. In addition, the protein expression level of nuclear factor erythroid 2-related factor (NRF2), a key regulator of oxidative stress, was also enhanced in OMPT-treated cells. Lastly, we verified that LPA3 plays a critical role in erastin-induced ferroptotic human erythroleukemia K562 cells. OMPT rescued the erythropoiesis defect caused by erastin in K562 cells based on a Gly A promoter luciferase assay. Taken together, our findings suggest that LPA3 activation inhibits cell ferroptosis by suppressing lipid oxidation and iron accumulation, indicating that ferroptosis could potentially serve as a link among LPA3, erythropoiesis, and aging.

Melatonin Relieves Paclitaxel-Induced Neuropathic Pain by Regulating pNEK2-Dependent Epigenetic Pathways in DRG Neurons.

The neurohormone melatonin (MLT) demonstrates promising potential in ameliorating neuropathic pain induced by paclitaxel (PTX) chemotherapy. However, little is known about its protective effect on dorsal root ganglion (DRG) neurons in neuropathic pain resulting from the chemotherapeutic drug PTX. Here, PTX-treated rats revealed that intrathecal administration of MLT dose-dependently elevated hind paw withdrawal thresholds and latency, indicating that MLT significantly reversed PTX-induced neuropathic pain. Mechanistically, the analgesic effects of MLT were found to be mediated via melatonin receptor 2 (MT2), as pretreatment with an MT2 receptor antagonist inhibited these effects. Moreover, intrathecal MLT injection reversed the pNEK2-dependent epigenetic program induced by PTX. All of the effects caused by MLT were blocked by pretreatment with an MT2 receptor-selective antagonist, 4P-PDOT. Remarkably, multiple MLT administered during PTX treatment (PTX+MLTs) exhibited not only rapid but also lasting reversal of allodynia/hyperalgesia compared to single-bolus MLT administered after PTX treatment (PTX+MLT). In addition, PTX+MLTs exhibited greater efficacy in reversing PTX-induced alterations in pRSK2, pNEK2, JMJD3, H3K27me3, and TRPV1 expression and interaction in DRG neurons than PTX+MLT. These results indicated that MLT administered during PTX treatment reduced the incidence and/or severity of neuropathy and had a better inhibitory effect on the pNEK2-dependent epigenetic program compared to MLT administered after PTX treatment. In conclusion, MLT/MT2 is a promising therapy for the treatment of pNEK2-dependent painful neuropathy resulting from PTX treatment. MLT administered during PTX chemotherapy may be more effective in the prevention or reduction of PTX-induced neuropathy and maintaining quality.

Low-Density Lipoprotein Cholesterol Is Not a Major Determinant of High-Sensitivity C-Reactive Protein Levels in People Without Known Diabetes Mellitus.

Background: It has been well established that high-sensitivity C-reactive protein (hs-CRP) is strongly associated with obesity, insulin resistance, high blood pressure, and dyslipidemia. However, the effects of different lipid parameters on hs-CRP levels are less deliberated. The purpose of the study was to compare the relative contribution of triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) to the levels of hs-CRP. Methods: Three hundred seventy-eight subjects without known history of diabetes were recruited for the study. No concomitant antilipid or antidiabetes agents were allowed. Each subject received anthropometric measurements, fasting sampling for lipid profile and hs-CRP, and a 75-gram oral glucose tolerance test for the measurements of insulin resistance (surrogated by insulin sensitivity index ISI0,120). Results: Levels of hs-CRP levels were positively correlated with Log (TG) and negatively correlated with HDL-C in partial correlation after adjustments for confounding variables, but not with LDL-C. The hs-CRP levels in the three groups by tertiles of LDL-C were similar. Subsequently, we found that body mass index (first step), Log (ISI0,120) (second step), and Log (TG) (third step) independently predicted the variance of Log (hs-CRP) in stepwise multiple regression. However, both HDL-C and LDL-C failed to be entered into the models to explain Log (hs-CRP). Conclusions: Our data demonstrated that Log (TG) was a major lipid determinant of hs-CRP levels. The contribution of LDL-C to the levels of hs-CRP might be insignificant.

Optimization of aqueous extraction of antioxidants from Chrysanthemum (C. morifolium Ramat and C. indicum L.) flowers and evaluation of their protection from glycoxidation damage on human αA-crystallin.

Chrysanthemum tea is commonly consumed by Chinese consumers mainly due to the Chrysanthemum flower being a potential source of antioxidants. The current study investigates the effects of extraction time and temperature on Chrysanthemum flower aqueous extract (CFAE) antioxidant capacity, including Trolox equivalent antioxidant capacity (TEAC), ferrous iron-chelating activity, and superoxide radical scavenging capacity (SRSC) using a two-factor, three-level factorial design of the response surface method (RSM). The TEAC and SRSC of CFAE are higher at higher temperatures and longer times up to a certain point, and the highest TEAC and SRSC are achieved at a 100 °C extraction temperature for 45 min. The fructose induced-αA-crystallin (Cry) glycation model system was used to evaluate the effects of the CFAE on anti-glycoxidation activities. The antioxidant ingredients obtained from CFAE significantly impede the production of advanced glycation end products from protein glycoxidation products (dityrosine, kynurenine, and N'-methylkynurenine) in the glycation process of αA-Cry and exhibit strong anti-glycating activity. The glycation inhibitory effects of CFAE are concentration-dependent. C. indicum L. exhibits greater potential for preventing cataracts compared to C. morifolium Ramat CFAE's antioxidant and anti-glycation properties suggest its potential application as a natural ingredient in the development of agents to combat glycation.

Photo-protection and photo-inhibition during light induction in Barbula indica and Conocephalum conicum under different light gradients.

The objectives of this study were to measure the chlorophyll fluorescence (ChlF) parameters of Barbula indica (Hook.) Spreng and Conocephalum conicum (L.) Dumort subjected to various light intensities (LI) as a reflection of their adaptability to their habitats. The electron transport rate (ETR) of all plants under 500 µmol m-2 s-1 photosynthetic photon flux density (PPFD) was significantly higher than other LI treatments, implying that these plants could be grown under a specific and optimal light intensity adapted to 500 PPFD conditions. As LI increased from 50 to 2,000 PPFD, we observed in all plants increased non-photochemical quenching (NPQ) and photo-inhibitory quenching (qI) and decreased photosystem II efficiency (ΦPSII), potential quantum efficiency of PSII (Fv/Fm), actual PSII efficiency (ΔF/Fm'%), and Fv/Fm%. In addition, energy-dependent quenching (qE), the light protection system (qE + qZ + qT), and qI increased as ΦPSII decreased and photo-inhibition% increased under 1000, 1500, and 2000 PPFD conditions, suggesting that these plants had higher photo-protective ability under high LI treatments to maintain higher photosynthetic system performance. B. indica plants remained photochemically active and maintained higher qE under 300, 500, and 1000 PPFD, whereas C. conicum qZ + qT exhibited higher photo-protection under 500, 1000, and 1500 PPFD conditions. These ChlF indices can be used for predicting photosynthetic responses to light induction in different bryophytes and provide a theoretical basis for ecological monitoring.

E2F7 drives autotaxin/Enpp2 transcription via chromosome looping: Repression by p53 in murine but not in human carcinomas.

Dysregulation of the autotaxin (ATX, Enpp2)-lysophosphatidic acid (LPA) signaling in cancerous cells contributes to tumorigenesis and therapy resistance. We previously found that ATX activity was elevated in p53-KO mice compared to wild-type (WT) mice. Here, we report that ATX expression was upregulated in mouse embryonic fibroblasts from p53-KO and p53R172H mutant mice. ATX promoter analysis combined with yeast one-hybrid testing revealed that WT p53 directly inhibits ATX expression via E2F7. Knockdown of E2F7 reduced ATX expression and chromosome immunoprecipitation showed that E2F7 promotes Enpp2 transcription through cooperative binding to two E2F7 sites (promoter region -1393 bp and second intron 996 bp). Using chromosome conformation capture, we found that chromosome looping brings together the two E2F7 binding sites. We discovered a p53 binding site in the first intron of murine Enpp2, but not in human ENPP2. Binding of p53 disrupted the E2F7-mediated chromosomal looping and repressed Enpp2 transcription in murine cells. In contrast, we found no disruption of E2F7-mediated ENPP2 transcription via direct p53 binding in human carcinoma cells. In summary, E2F7 is a common transcription factor that upregulates ATX in human and mouse cells but is subject to steric interference by direct intronic p53 binding only in mice.

N-Formimidoylation/-iminoacetylation modification in aminoglycosides requires FAD-dependent and ligand-protein NOS bridge dual chemistry.

Oxidized cysteine residues are highly reactive and can form functional covalent conjugates, of which the allosteric redox switch formed by the lysine-cysteine NOS bridge is an example. Here, we report a noncanonical FAD-dependent enzyme Orf1 that adds a glycine-derived N-formimidoyl group to glycinothricin to form the antibiotic BD-12. X-ray crystallography was used to investigate this complex enzymatic process, which showed Orf1 has two substrate-binding sites that sit 13.5 Å apart unlike canonical FAD-dependent oxidoreductases. One site could accommodate glycine and the other glycinothricin or glycylthricin. Moreover, an intermediate-enzyme adduct with a NOS-covalent linkage was observed in the later site, where it acts as a two-scissile-bond linkage facilitating nucleophilic addition and cofactor-free decarboxylation. The chain length of nucleophilic acceptors vies with bond cleavage sites at either N-O or O-S accounting for N-formimidoylation or N-iminoacetylation. The resultant product is no longer sensitive to aminoglycoside-modifying enzymes, a strategy that antibiotic-producing species employ to counter drug resistance in competing species.

Asiatic acid exhibits antimetastatic activity in human prostate cancer cells by modulating the MZF-1/Elk-1/Snail signaling axis.

Prostate cancer metastasis is associated with poor prognosis and is difficult to treat clinically. Numerous studies have shown that Asiatic Acid (AA) has antibacterial, anti-inflammatory, and antioxidant effects. However, the effect of AA on prostate cancer metastasis is still unclear. This purpose of this study is to investigate the effect of AA on prostate cancer metastasis and to better understand its molecular mechanisms of action. Our results indicate that AA ≤ 30 µM did not influence cell viability and cell cycle distribution in PC3, 22Rv1 and DU145 cells. AA inhibited the migratory and invasive capabilities of three prostate cancer cells to be due to its effects on Snail, but did not have activity on Slug. We observed that AA inhibited the Myeloid zinc finger 1 (MZF-1) and ETS Like-1 (Elk-1) protein interaction and affected the complex's binding capacity to the Snail promoter region, ultimately blocking Snail transcription activity. Kinase cascade analysis revealed that phosphorylation of MEK3/6 and p38MAPK was inhibited by AA treatment. Moreover, knockdown of p38MAPK enhanced AA-suppressed protein levels of MZF-1, Elk-1, and Snail, suggesting that p38MAPK influences prostate cancer cell metastasis. These results provide promise for AA as a future candidate in the development of drug therapies to prevent or treat prostate cancer metastasis.

Paclitaxel exerts antiplatelet and antithrombotic activities: Additional benefit from use of paclitaxel-coated balloons and -eluting stents in coronary revascularization and prevention of in-stent restenosis.

INTRODUCTION: Paclitaxel is a microtubule-stabilizing drug used to treat several types of cancer, including ovarian and breast cancer. Because of its antiproliferative effect on vascular smooth muscle cells, balloons and stents are coated with paclitaxel for use in coronary revascularization and prevention of in-stent restenosis (ISR). However, mechanisms underlying ISR are complicated. Platelet activation is one of the major causes of ISR after percutaneous coronary intervention. Although the antiplatelet activity of paclitaxel was noted in rabbit platelets, the effect of paclitaxel on platelets remains unclear. This study investigated whether paclitaxel exhibits antiplatelet activity in human platelets. METHODS AND RESULTS: Paclitaxel inhibited platelet aggregation induced by collagen but not that induced by thrombin, arachidonic acid, or U46619, suggesting that paclitaxel is more sensitive to the inhibition of collagen-induced platelet activation. Moreover, paclitaxel blocked collagen receptor glycoprotein (GP) VI downstream signaling molecules, including Lyn, Fyn, PLCγ2, PKC, Akt, and MAPKs. However, paclitaxel did not directly bind to GPVI and cause GPVI shedding, as detected by surface plasmon resonance and flow cytometry, respectively, indicating that paclitaxel may interfere with GPVI downstream signaling molecules, such as Lyn and Fyn. Paclitaxel also prevented granule release and GPIIbIIIa activation induced by collagen and low convulxin doses. Moreover, paclitaxel attenuated pulmonary thrombosis and delayed platelet thrombus formation in mesenteric microvessels without significantly affecting hemostasis. CONCLUSION: Paclitaxel exerts antiplatelet and antithrombotic effects. Thus, paclitaxel may provide additional benefits beyond its antiproliferative effect when used in drug-coated balloons and drug-eluting stents for coronary revascularization and prevention of ISR.

A novel method for visualizing in-vivo rates of protein degradation provides insight into how TRIM28 regulates muscle size.

Skeletal muscle size is controlled by the balance between protein synthesis and protein degradation. Given the essential role of skeletal muscle in maintaining a high quality of life, understanding the mechanisms that modulate this balance are of critical importance. Previously, we demonstrated that muscle-specific knockout of TRIM28 reduces muscle size and function and in the current study, we discovered that this effect is associated with an increase in protein degradation and a dramatic reduction in the expression of Mettl21c. Importantly, we also determined that overexpression of Mettl21c is sufficient to induce hypertrophy in both control and TRIM28 knockout muscles. Moreover, we developed a simple pulse-chase biorthogonal non-canonical amino acid tagging technique that enabled us to visualize the in vivo rate of protein degradation, and with this technique were able to conclude that the hypertrophic effect of Mettl21c is due, at least in part, to an inhibition of protein degradation.

Responses of photosynthesis and chlorophyll fluorescence during light induction in different seedling ages of Mahonia oiwakensis.

BACKGROUND: The aim of this study was to determine the actual state of the photosynthetic apparatus and exhibit distinguishable differences in the chlorophyll fluorescence (ChlF) components in different seedling ages of M. oiwakensis plants subjected to different light intensity (LI). Potted 6-month-old greenhouse seedlings and field collected 2.4-year-old seedlings with 5 cm heights were selected and randomly separated into seven groups for photosynthesis measurements illuminated with 50, 100 (assigned as low LI), 300, 500, 1,000 (as moderate LI), 1,500 and 2,000 (as high LI) µmol m-2 s-1 photosynthetic photon flux density (PPFD) treatments. RESULTS: n 6-month-old seedlings, as LI increased from 50 to 2,000 PPFD, the values of non-photochemical quenching and photo-inhibitory quenching (qI) increased but potential quantum efficiency of PSII (Fv/Fm) and photochemical efficiency of photosystem II (ΦPSII) values decreased. High electron transport rate and percentage of actual PSII efficiency by Fv/Fm values were observed in 2.4-year-old seedlings at high LI conditions. Furthermore, higher ΦPSII was detected under low LI conditions, with lower energy-dependent quenching (qE) and qI values and photo-inhibition % decreased as well. However, qE and qI increased as ΦPSII decreased and photo-inhibition% increased under high LI treatments. CONCLUSIONS: These results could be useful for predicting the changes in growth and distribution of Mahonia species grown in controlled environments and open fields with various combinations of varying light illuminations, and ecological monitoring of their restoration and habitat creation is important for provenance conservation and helps to formulate better conservation strategies for the seedlings.

Phosphorylated Upstream Frameshift 1-dependent Nonsense-mediated µ-Opioid Receptor mRNA Decay in the Spinal Cord Contributes to the Development of Neuropathic Allodynia-like Behavior in Rats.

BACKGROUND: Nonsense-mediated messenger RNA (mRNA) decay increases targeted mRNA degradation and has been implicated in the regulation of gene expression in neurons. The authors hypothesized that nonsense-mediated µ-opioid receptor mRNA decay in the spinal cord is involved in the development of neuropathic allodynia-like behavior in rats. METHODS: Adult Sprague-Dawley rats of both sexes received spinal nerve ligation to induce neuropathic allodynia-like behavior. The mRNA and protein expression contents in the dorsal horn of animals were measured by biochemical analyses. Nociceptive behaviors were evaluated by the von Frey test and the burrow test. RESULTS: On Day 7, spinal nerve ligation significantly increased phosphorylated upstream frameshift 1 (UPF1) expression in the dorsal horn (mean ± SD; 0.34 ± 0.19 in the sham ipsilateral group vs. 0.88 ± 0.15 in the nerve ligation ipsilateral group; P < 0.001; data in arbitrary units) and drove allodynia-like behaviors in rats (10.58 ± 1.72 g in the sham ipsilateral group vs. 1.19 ± 0.31 g in the nerve ligation ipsilateral group, P < 0.001). No sex-based differences were found in either Western blotting or behavior tests in rats. Eukaryotic translation initiation factor 4A3 (eIF4A3) triggered SMG1 kinase (0.06 ± 0.02 in the sham group vs. 0.20 ± 0.08 in the nerve ligation group, P = 0.005, data in arbitrary units)-mediated UPF1 phosphorylation, leading to increased nonsense-mediated mRNA decay factor SMG7 binding and µ-opioid receptor mRNA degradation (0.87 ± 0.11-fold in the sham group vs. 0.50 ± 0.11-fold in the nerve ligation group, P = 0.002) in the dorsal horn of the spinal cord after spinal nerve ligation. Pharmacologic or genetic inhibition of this signaling pathway in vivo ameliorated allodynia-like behaviors after spinal nerve ligation. CONCLUSIONS: This study suggests that phosphorylated UPF1-dependent nonsense-mediated µ-opioid receptor mRNA decay is involved in the pathogenesis of neuropathic pain.

Phosphate NIMA-Related Kinase 2-Dependent Epigenetic Pathways in Dorsal Root Ganglion Neurons Mediates Paclitaxel-Induced Neuropathic Pain.

BACKGROUND: The microtubule-stabilizing drug paclitaxel (PTX) is an important chemotherapeutic agent for cancer treatment and causes peripheral neuropathy as a common side effect that substantially impacts the functional status and quality of life of patients. The mechanistic role for NIMA-related kinase 2 (NEK2) in the progression of PTX-induced neuropathic pain has not been established. METHODS: Adult male Sprague-Dawley rats intraperitoneally received PTX to induce neuropathic pain. The protein expression levels in the dorsal root ganglion (DRG) of animals were measured by biochemical analyses. Nociceptive behaviors were evaluated by von Frey tests and hot plate tests. RESULTS: PTX increased phosphorylation of the important microtubule dynamics regulator NEK2 in DRG neurons and induced profound neuropathic allodynia. PTX-activated phosphorylated NEK2 (pNEK2) increased jumonji domain-containing 3 (JMJD3) protein, a histone demethylase protein, to specifically catalyze the demethylation of the repressive histone mark H3 lysine 27 trimethylation (H3K27me3) at the Trpv1 gene, thereby enhancing transient receptor potential vanilloid subtype-1 (TRPV1) expression in DRG neurons. Moreover, the pNEK2-dependent PTX response program is regulated by enhancing p90 ribosomal S6 kinase 2 (RSK2) phosphorylation. Conversely, intrathecal injections of kaempferol (a selective RSK2 activation antagonist), NCL 00017509 (a selective NEK2 inhibitor), NEK2-targeted siRNA, GSK-J4 (a selective JMJD3 inhibitor), or capsazepine (an antagonist of TRPV1 receptor) into PTX-treated rats reversed neuropathic allodynia and restored silencing of the Trpv1 gene, suggesting the hierarchy and interaction among phosphorylated RSK2 (pRSK2), pNEK2, JMJD3, H3K27me3, and TRPV1 in the DRG neurons in PTX-induced neuropathic pain. CONCLUSIONS: pRSK2/JMJD3/H3K27me3/TRPV1 signaling in the DRG neurons plays as a key regulator for PTX therapeutic approaches.

The role of satellite cell-derived TRIM28 in mechanical load- and injury-induced myogenesis.

Satellite cells are skeletal muscle stem cells that contribute to postnatal muscle growth, and they endow skeletal muscle with the ability to regenerate after a severe injury. Here we discovered that this myogenic potential of satellite cells requires a protein called tripartite motif-containing 28 (TRIM28). Unexpectedly, multiple lines of both in vitro and in vivo evidence revealed that the myogenic function of TRIM28 is not dependent on changes in the phosphorylation of its serine 473 residue. Moreover, the functions of TRIM28 were not mediated through the regulation of satellite cell proliferation or differentiation. Instead, our findings indicate that TRIM28 regulates the ability of satellite cells to progress through the process of fusion. Specifically, we discovered that TRIM28 controls the expression of a fusogenic protein called myomixer and concomitant fusion pore formation. Collectively, the outcomes of this study expose the framework of a novel regulatory pathway that is essential for myogenesis.

Physiological responses and antioxidant properties of coriander plants (Coriandrum sativum L.) under different light intensities of red and blue lights.

Coriander (Coriandrum sativum L.) contains abundant antioxidants and essential oils which can provide antibacterial, antifungal, and antioxidant activities in the pharmaceutical, health and food production industry. To improve the economic values of coriander, the relationships between optimal light treatments for maximizing both plant growth and the antioxidant and essential oil content of coriander leaves need to be determined. Plants were exposed to five light-emitting diodes spectral color mixtures, high blue light (BL) intensity induced the levels of reducing power response. The light treatments were then adjusted for the analysis of secondary metabolite compounds of coriander leaves. Among 30 identified compounds, the amounts of decamethyl-cyclopentasiloxane and dodecane were significantly reduced in the R80 + G50 + B50 condition, whereas dodecamethyl-cyclohexasiloxane level was significantly reduced in R50 + G50 + B80 condition. Various light quality and intensity combinations influenced the accumulations of chlorophyll and phytochemical contents, mediated antioxidative properties, and secondary metabolites of coriander leaves, which may be useful in developing a new LED lighting apparatus optimized for coriander production in plant factories.

Photosynthesis in Response to Different Salinities and Immersions of Two Native Rhizophoraceae Mangroves.

Mangrove ecosystems are vulnerable to rising sea levels as the plants are exposed to high salinity and tidal submergence. The ways in which these plants respond to varying salinities, immersion depths, and levels of light irradiation are poorly studied. To understand photosynthesis in response to salinity and submergence in mangroves acclimated to different tidal elevations, two-year-old seedlings of two native mangrove species, Kandelia obovata and Rhizophora stylosa, were treated at different salinity concentrations (0, 10, and 30 part per thousand, ppt) with and without immersion conditions under fifteen photosynthetic photon flux densities (PPFD µmol photon·m-2·s-1). The photosynthetic capacity and the chlorophyll fluorescence (ChlF) parameters of both species were measured. We found that under different PPFDs, electron transport rate (ETR) induction was much faster than photosynthetic rate (Pn) induction, and Pn was restricted by stomatal conductance (Gs). The Pn of the immersed K. obovata plants increased, indicating that this species is immersed-tolerant, whereas the Pn level of the R. stylosa plants is salt-tolerant with no immersion. All of the plants treated with 30 ppt salinity exhibited lower Pn but higher non-photochemical quenching (NPQ) and heat quenching (D) values, followed by increases in the excess energy and photoprotective effects. Since NPQ or D can be easily measured in the field, these values provide a useful ecological monitoring index that may provide a reference for mangrove restoration, habitat creation, and ecological monitoring.