The Regulation of Nitrate Reductases in Response to Abiotic Stress in Arabidopsis TRANSLATE Journal: International Journ

The two homologous genes, NIA1 and NIA2, encode nitrate reductases in Arabidopsis, which govern the reduction of nitrate to nitrite. This step is the rate-limiting step of the nitrate assimilation and utilization. Therefore, the regulation of NIA1 and NIA2 is important for plant development and growth. Although they are similar in sequence and structure, their regulations are different. Genetic analysis uncovers that NIA1, rather than NIA2, plays a predominant role in adopting to ABA stress. Although both long-term stress conditions can cause an improvement in NIA1 levels, a decrease in NIA1 levels under short-term treatments seems to be necessary for plants to switch from the growth status into the adopting status. Interestingly, the downregulation of the NR is distinct under different stress conditions. Under ABA treatment, the NR proteins are degraded via a 26S-proteasome dependent manner, while the transcriptional regulation is the main manner to rapidly reduce the NIA1 levels under nitrogen deficiency and NaCl stress conditions. These results indicate that under stress conditions, the regulation of NIA1 is complex, and it plays a key role in regulating the balance between growth and adaptation.

Evaluation of the Simpson’s Method to Determine Left Ventricular Ejection Fraction Using the Transgastric Two-Chamber View

Introduction: Left ventricular chamber size and functional assessment by transesophageal echocardiography can be difficult if visualization is poor in the mid-esophageal views. However, the accuracy of using the Simpson’s method in the transgastric 2-chamber (TG2C) as an alternative approach has not been assessed.
Methods: The Simpson’s method was performed by 2 independent reviewers using midesophageal 2-chamber (ME2C) and TG2C views. Echocardiographic images were retrieved retrospectively for 49 adult cardiac surgical patients.
Results: Two-way random effects intraclass correlation coefficients demonstrated no significant interobserver variability. Linear mixed effects models showed no significant differences in ME2C and TG2C measurements with regard to EDV (P=.4407), ESV (P=.5113), or EF (P=.0610).Compared to the ME2C view, the TG2C view had better image quality of the LV walls (image quality score median [interquartile range]: 2.00 [.00] vs 1.00 [1.00]; P<.0001), but worse image quality of the mitral annulus (1.00 [1.00] vs 2.00 [.00]; P<.0001) and LV apex (.00 [1.00] vs 2.00 [1.00]; P<.0001).
Conclusions: This study suggests the Simpson’s method can be applied to the TG2C view as an alternative to the standard midesophageal method to estimate chamber volumes and EF.
Keywords: Simpson’s method; intraoperative assessment; left ventricular ejection fraction; monitoring; research; transesophageal echocardiography.

Intracellular MUC20 variant 2 maintains mitochondrial calcium homeostasis and enhances drug resistance in gastric cancer

Background: Signet ring cell carcinoma (SRCC) is a particular histologic variant of gastric cancer (GC). However, the critical factor related to the aggressive characteristics of SRCC has not been determined.
Methods: We collected surgically resected tissues from 360 GC patients in the Kumamoto University cohort and generated survival curves via the Kaplan-Meier method. In vitro, we identified the specific transcript variant of MUC20 in SRCC cells by direct sequencing and investigated the role of MUC20 in GC progression using GC cells with MUC20 silencing and forced expression. In vivo, we examined chemoresistance using MUC20 variant 2 (MUC20v2)-overexpressing non-SRCC cells to construct a xenograft mouse model.
Results: We analyzed a comprehensive GC cell line database to identify the specifically expressed genes in gastric SRCC. We focused on MUC20 and investigated its role in GC progression. Survival analysis revealed that GC patients with high MUC20 expression exhibited a poor prognosis and that MUC20 expression was significantly correlated with SRCC histological type. Moreover, we found that gastric SRCC cells specifically expressed MUC20v2, which was dominantly expressed in the cytoplasm. Silencing MUC20v2 caused cell death with characteristic morphological changes in gastric SRCC cells. To further determine the types of cell death, we examined apoptosis, pyroptosis and ferroptosis by detecting cleaved PARP, gasdermin E-N-terminal (GSDME-N), and lipid reactive oxygen species (ROS) levels, respectively. We found that apoptosis and pyroptosis occurred in MUC20-silenced gastric SRCC cells. In addition, MUC20v2-overexpressing GC cells exhibited chemoresistance to cisplatin (CDDP) and paclitaxel (PTX). RNA sequencing revealed that the pathways involved in intracellular calcium regulation were significantly upregulated in MUC20v2-overexpressing GC cells.
Notably, forced expression of MUC20v2 in the cytoplasm of GC cells led to the maintenance of mitochondrial calcium homeostasis and mitochondrial membrane potential (MMP), which promoted cell survival and chemoresistance by suppressing apoptosis and pyroptosis. Finally, we investigated the significance of MUC20v2 in a xenograft model treated with CDDP and showed that MUC20v2 overexpression caused chemoresistance by inhibiting cell death.
Conclusion: These findings highlight the novel functions of MUC20v2, which may confer cell survival and drug resistance in GC cells.
Significance: MUC20v2 protects GC cells from apoptosis and pyroptosis by maintaining mitochondrial calcium levels and mitochondrial membrane potential and subsequently induces drug resistance.
Keywords: Drug resistance; Intracellular mucin 20; Mitochondrial calcium homeostasis; Mitochondrial membrane potential; Signet ring cell carcinoma.

Antioxidant, Antimicrobial Activities and Characterization of Polyphenol-Enriched Extract of Egyptian Celery ( Apium graveolens L., Apiaceae) Aerial Parts via UPLC/ESI/TOF-MS

Medicinal plant extracts are increasingly considered a major source of innovative medications and healthcare products.
This study focused on preparing a polyphenol enriched water extract of Egyptian celery “Apium graveolens L., Apiaceae” aerial parts (TAE) in an endeavor to accentuate its antioxidant capacity as well as its antimicrobial activity. (TAE) of celery was partitioned against different organic solvents to yield dichloromethane (DCM), ethyl acetate (EAC), and butanol (BUOH) fractions. (TAE) and the organic fractions thereof besides the remaining mother liquor (ML) were all screened for their antioxidant capacity using various protocols viz. monitoring the reducing amplitudes for ferric ions (FRAP), and radical scavenging potentials of oxygen (ORAC), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and metal chelation assays.
The examination procedure revealed both (TAE) extract and (DCM) fraction, to pertain the highest antioxidant potentials, where the IC50 of the (TAE) using ABTS and metal chelation assays were ca. 34.52 ± 3.25 and 246.6 ± 5.78 µg/mL, respectively. The (DCM) fraction recorded effective results using the FRAP, ORAC, and DPPH assays ca. 233.47 ± 15.14 and 1076 ± 25.73 μM Trolox equivalents/mg sample and an IC50 474.4 ± 19.8 µg/mL, respectively.
Additionally, both (TAE) and (DCM) fraction exerted antimicrobial activities recording inhibition zones (mm) (13.4 ± 1.5) and (12.0 ± 1.0) against Staphylococcus aureus and (11.0 ± 1.2) and (10.0 ± 1.3) against Escherichia coli, respectively, with no anti-fungal activity. Minimum inhibitory concentration (MIC) of (TAE) and (DCM) fraction were 1250 and 2500 µg/mL, respectively. UPLC/ESI/TOF-MS unveiled the chemical profile of both (TAE) and (DCM) fraction to encompass a myriad of active polyphenolic constituents including phenylpropanoids, coumarins, apigenin, luteolin, and chrysoeriol conjugates.

Real world data on cardiometabolic diseases in U.S. adults during the SARS-CoV-2 pandemic: a decentralized registry study

Background: Pre-existing cardiometabolic comorbidities place SARS-CoV-2 positive patients at a greater risk for poorer clinical course and mortality than those without it. We aimed to analyze real-world registry data focused primarily on participants with cardiometabolic diseases (CMD), which were remotely obtained via a digital platform.
Methods: Participants were divided into two groups: CMD or no cardiometabolic disease (non-CMD). They were evaluated based on their medical history, current medications/supplements, COVID-19 status, demographics, and baseline characteristics. The frequency of medications/supplements for CMD were compared using relative risks and 95% confidence intervals. The WHO (Five) Well-Being Index (WHO-5) were collected monthly for 6 months to assess psychological well-being which included cheerfulness, calmness, vigor, rest, and engagement with daily activities of interest.
Results: The 791 enrollees represented 49 U.S. states.
The CMD group had significantly higher (p < 0.0001) BMI (mean + 3.04 kg/m2) and age (mean + 9.15 years) compared to non-CMD group. In the CMD group, participants who tested positive for COVID-19 had lower (p < 0.0001) well-being scores than those without COVID-19. For the 274 participants on CMD medications/supplements, there was no statistical difference in risk of COVID-19 contracture based on medication/supplement type; however, all six participants who were not being treated for CMD were COVID-19 positive (RR ~ 104). For 89 participants who were on treatment for diabetes or insulin resistance, there was a 90% reduced risk of COVID-19 incidence (p = 0.0187).

Formulated DMEM

from Addexbio
C0003-01 | RT 500 mL Bottle: 98.00 EUR

Optimized DMEM

from Addexbio
C0003-02 | RT 500 mL Bottle: 100.00 EUR

Specialized DMEM

from Addexbio
C0003-03 | RT 500 mL Bottle: 104.00 EUR

DMEM, High Glucose

from GenDepot
CM001-050 | 500ml: 72.00 EUR

DMEM, High Glucose

from GenDepot
CM001-300 | 6x500ml: 158.00 EUR

DMEM, High Glucose

from GenDepot
CM001-310 | 10x500ml: 201.00 EUR

DMEM, High Glucose

from GenDepot
CM001-320 | 20x500ml: 313.00 EUR

DMEM, High Glucose

from GenDepot
CM001-350 | 50x500ml: 571.00 EUR

DMEM, High Glucose

from GenDepot
CM002-050 | 500ml: 72.00 EUR

DMEM, High Glucose

from GenDepot
CM002-300 | 6x500ml: 158.00 EUR

DMEM, High Glucose

from GenDepot
CM002-310 | 10x500ml: 201.00 EUR
Conclusion: The well-being score of the CMD group was dependent on whether they tested positive for COVID-19. Type of CMD treatment did not impact COVID-19 status, but absence of treatment significantly increased COVID-19 incidence. With respect to SARS-CoV-2, our analysis supports continued use of the statins, ACE-I, ARBs, and diabetes medications in CMD patients.
Trial registration: ClinicalTrials.gov Identifier: NCT04348942.
Keywords: Angiotensin; Cardiovascular; Diabetes; Insulin resistance; Metabolism; SARS-CoV-2.

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