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Sodium glucose cotransporter‐2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon‐like peptide‐1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, −0.41%, P, In the randomized controlled trial, long‐term ipragliflozin treatment ameliorates hepatic outcomes, including fibrosis, in patients with type 2 diabetes with NAFLD. Ipragliflozin also ameliorates obesity and glycemic control in patients with type 2 diabetes with NAFLD.

Little is known about the long-term impact of apolipoprotein E (apoE) on residual cardiovascular risk in patients with chronic coronary syndrome (CCS) receiving statin treatment.A total of 1109 consecutive patients (mean age, 67 ± 10 years; 83% men) with CCS who underwent their first intervention between 2000 and 2016 were included in this study. All patients had achieved low-density lipoprotein cholesterol (LDL-C)100 mg/dL on statin treatment and were divided into two groups based on median serum apoE values. We evaluated the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, and target vessel revascularization.A total of 552 and 557 patients were categorized to the higher and lower apoE groups, respectively. There were significant relationships between apoE levels and total cholesterol levels, triglyceride levels, high-density lipoprotein cholesterol levels, and estimated remnant cholesterol, except for LDL-C levels. During the median follow-up period of 5.1 years, 195 patients (17.6%) developed MACEs. Kaplan-Meier analysis revealed that the cumulative incidence of MACEs in the higher apoE group was significantly higher than in the lower apoE group (29.5% vs.23.8% log-rank test, p = 0.019). Using multivariable Cox hazard analysis, serum apoE level (1-mg/dL increase) (hazard ratio 1.15; 95% confidence interval 1.03-1.29, p = 0.013) was the strongest independent predictor of MACEs.Serum apoE level could be a strong predictor of residual cardiovascular risk in patients with CCS long-term, even if LDL-C levels are controlled with statin treatment.

Modification of titania supports for iridium catalysts by phosphorus species greatly enhanced the activity for the synthesis of benzimidazoles via hydrogen transfer. Two series of phosphorus-modified titanias were used: The iridium catalysts supported on phosphorus-doped rutile titania prepared by the hydrothermal method showed nearly 5 times higher activity for the reaction of 2-nitroaniline (1a) and benzyl alcohol (2a) to 2-phenylbenzimidazole (3aa) than the catalysts supported on unmodified rutile. XPS depth profile study substantiated that the dopant was present mainly on the surface of the rutile support. Therefore, a facile wet impregnation method was applied to modify the surface of anatase titania with phosphoric acid. The use of thus-modified titania enhanced the activity of the iridium catalysts by more than 2.7 times. The FTIR and XPS studies revealed the presence of bidentate phosphorus species on the surface of titania, and the H2-TPR study indicated that phosphorus-modification promoted the formation of iridium species reduced at higher temperature, which would be suitable for the present catalysis.

Magnesium silicide (Mg2Si) is a promising eco-friendly thermoelectric material, which has been extensively studied in recent times. However, its phase behavior at high pressures and temperatures remains unclear. To this end, in this study, in situ X-ray diffraction analysis was conducted at high pressures ranging from 0 to 11.3 GPa and high temperatures ranging from 296 to 1524 K, followed by quenching. The antifluorite-phase Mg2Si decomposed to Mg9Si5 and Mg at pressures above 3 GPa and temperatures above 970 K. The antifluorite-phase Mg2Si underwent a structural phase transition to yield a high-pressure room-temperature (HPRT) phase at pressures above 10.5 GPa and at room temperature. This HPRT phase also decomposed to Mg9Si5 and Mg when heated at ∼11 GPa. When 5Mg2Si decomposed to Mg9Si5 and Mg, the volume reduced by ∼6%. Mg9Si5 synthesized at high pressures and high temperatures was quenchable under ambient conditions. Thermoelectric property measurements of Mg9Si5 at temperatures ranging from 10 to 390 K revealed that it was a p-type semiconductor having a dimensionless thermoelectric figure of merit (ZT) of 3.4 × 10-4 at 283 K.

Fluorescent probes are powerful tools for visualizing cellular and subcellular structures, their dynamics and cellular molecules in living cells and enable us to monitor cellular processes in a spatiotemporal manner within complex and crowded systems. In addition to popular fluorescent proteins, a wide variety of small-molecule dyes have been synthesized through close association with the interdisciplinary field of chemistry and biology, ranging from those suitable for labeling cellular compartments such as organelles to those for labeling intracellular biochemical and biophysical processes and signaling. In recent years, self-labeling technologies including the SNAP-tag system have allowed us to attach these dyes to cellular domains or specific proteins and are beginning to be employed in plant studies. In this mini review, we will discuss the current range of synthetic fluorescent probes that have been exploited for live-cell imaging and the recent advances in the application that enable genetical tagging of synthetic probes in plant research.

The 70% ethanol extract of Artemisia campestris was screened to find PPARγ ligands using the PPARγ ligand-responsive chimera luciferase reporter system. Capillartemisin B was identified as a PPARγ ligand that stimulated lipid accumulation in 3T3-L1 cells. By further purification of PPARγ ligands from a large-scale preparation of the methanol extract of Artemisia campestris, we isolated and identified eupatilin and santaflavone as PPARγ ligands. Weak PPARγ ligand activity of eupatilin or santaflavone in reporter assay was enhanced by a PPARγ antagonist, GW9662, suggesting that santaflavone or eupatilin and GW9662 bound simultaneously to the multiple sub-pockets of the PPARγ ligand-binding domain (LBD) and cooperatively activated PPARγ. Docking simulation suggested that eupatilin binds to the Ω-pocket but not to the AF-2 pocket of Y-shaped PPARγ LBD where artepillin C that differs from capillartemisin B at the C-5′ position without hydroxy group binds. Eupatilin or santaflavone with or without GW9662 did not stimulate lipid accumulation in differentiated 3T3-L1 cells, suggesting that binding of each compound alone or with GW9662 to the Ω-pocket which stimulated the PPARγ-responsive reporter expression was not enough to stimulate lipid accumulation. The PPARγ ligands found in this study have a potential to design the fragment-based drug design of a novel PPARγ ligand that cover the Y-shaped PPARγ LBD.

Metals contents were determined in 18 samples of Extra Virgin Olive Oil (EVOO) collected from different regions in Tunisia, after microwave digestion with nitric acid and hydrogen peroxide. In oil obtained by the detection power of the ICP–MS technique was sufficient for the determination of trace metals. Oils were extracted using Lab Olive Oil Extractor Machine. The amounts of trace metals in EVOO were lower than the maximum values recommended by FAO/WHO expert committee on food and addictives and US environmental protection agency. Acidity value, K270 and K232 were also determined. The assessment of metal contents in EVOO showed significant differences (p

The aim of this study was to investigate the antioxidant, anti-inflammatory, and anticancer properties of two Tunisian Ephedra species (E. alata and E. fragilis) through their phytochemical constituents. The ethanol extract of E. alata exhibited potent antioxidant power activities and highpolyphenol contents. The ethyl acetate extract of this species possessedanticancer activity against cancerous cells MCF-7 (IC50 = 26 and 16 µg/mL in MTT and resazurin tests, respectively) as well as non cancerous cells Vero and H9C2 (IC50 = 143 and 22 µg/mL using MTT assay and 49 and 12 µg/mL using resazurin test, respectively). Besides, the ethyl acetate extracts 1 E. alata and E. fragilis showed an important anti-inflammatory effect inhibiting NO (62% and 70% at 50 µg/mL, respectively). Subsequent analysis of the active fractions using LC-DAD revealed that chlorogenic acid, caffeic acid, gallic acid, quercetin and isoquercitrin were the main bioactive molecules which might be responsible for their antioxidant, anticancer and anti-inflammatory properties. Overall, the results suggested that the two Ephedra species are valuable sources of natural agents beneficial for human health.

Cerebral malaria is one of the most severe pathologies of malaria; it induces neuro-cognitive sequelae and has a high mortality rate. Although many factors involved in the development of cerebral malaria have been discovered, its pathogenic mechanisms are still not completely understood. Most studies on cerebral malaria have focused on the blood-brain barrier, despite the importance of the blood-cerebrospinal fluid barrier, which protects the brain from peripheral inflammation. Consequently, the pathological role of the blood-cerebrospinal fluid barrier in cerebral malaria is currently unknown. To examine the status of the blood-cerebrospinal fluid barrier in cerebral malaria and malaria without this pathology (non-cerebral malaria), we developed a new method for evaluating the permeabilization of the blood-cerebrospinal fluid barrier during cerebral malaria in mice, using Evans blue dye and a software-assisted image analysis. Using C57BL/6J (B6) mice infected with Plasmodium berghei ANKA strain as an experimental cerebral malaria model and B6 mice infected with P. berghei NK65 strain or Plasmodium yoelii as non-cerebral malaria models, we revealed that the permeability of the blood-cerebrospinal fluid barrier increased during experimental cerebral malaria but not during non-cerebral malaria. We observed haemorrhaging in the cerebral ventricles and hemozoin-like structures in the choroid plexus, which is a key component of the blood-cerebrospinal fluid barrier, in cerebral malaria mice. Taken together, this evidence indicates that the blood-cerebrospinal fluid barrier is disrupted in experimental cerebral malaria, whereas it remains intact in non-cerebral malaria. We also found that P. berghei ANKA parasites and CD8+ T cells are involved in the blood-cerebrospinal fluid barrier disruption in experimental cerebral malaria. An understanding of the mechanisms underlying cerebral malaria might help in the development of effective strategies to prevent and manage cerebral malaria in humans.

Mung bean (Vigna radiata) is an immunomodulatory medicinal plant, which is recognized as a component of a traditional postpartum diet. The liver plays a crucial role in fatty acid synthesis under t...

Although highly challenging, spontaneous crystallization without racemization can be an innovative strategy for the facile preparation of an enantioselective conglomerate with planar chirality. The...

Stretchable physical sensors are crucial for the development of advanced electrical systems, particularly wearable devices and soft robotics. Currently available stretchable sensors that detect both pressure and strain are based on piezoelectric, piezoresistive, or piezocapacitive effects. The range of pressure sensing is 1–800 kPa with large deformations being within the range of deformations of parts of the human body, such as elbows and knees. However, these devices cannot easily allow simultaneous and independent detection of pressure and strain with sensor arrays at large tensions (> 50%) because strain affects the pressure signal. In this study, we propose a monolithic silicone-based array of pressure and strain sensors that can simultaneously and independently detect the in-plane biaxial tensile deformation and pressure. To realize these functionalities, the deformation of the device structure was optimized using a hetero-silicone substrate made of two types of silicone with different hardness characteristics and porous silicone bodies. In addition, the resistances of the sensors were controlled by adjusting a mixture based on carbon nanoparticles to improve the sensitivity and independence between the pressure and strain sensors. These concepts demonstrate the potential of this approach and its compatibility with the current architectures of stretchable physical sensors.

Artemisia herba-alba (Aha) is an aromatic and medicinal plant rich in health-promoting flavonoids compounds that play an important role as antioxidant. For better utilization of this resource, the ...

Stylissatin A (SA) is a cyclic heptapeptide isolated from the marine sponge Stylissa massa. SA shows anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells, but the detailed mechanism of action remains unclear. Here we report that D-Tyr1-tBuSA, a more potent SA derivative, inhibited production of the proinflammatory cytokines Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in LPS-stimulated RAW264.7 cells (EC50 = 1.4 and 5.9 μM, respectively). This compound also inhibited the LPS-stimulated expression of inducible nitric oxide synthase (iNOS) at 20 μM. Using a biotin derivative of SA, acyl-CoA dehydrogenase long chain (ACADL) was identified as a target protein of SA and its derivatives. It is proposed that SA and its derivatives might suppress the β-oxidation of fatty acids by ACADL, and the accumulation of fatty acids on macrophages would inhibit the nuclear factor-kappa B (NF-κB) signaling pathway and iNOS expression to show anti-inflammatory activity. Our research might provide a new mechanism of inflammation in macrophages, and contribute to the development of treatments for inflammatory diseases.

The skin color is imparted by the pigment melanin produced in the melanosomes of melanocytes, through the catalytic action of melanogenesis enzymes tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase. Disruptions in the melanogenesis process may result to hypopigmentation, as observed in cutaneous postinflammatory conditions. Here, the bioactivity of tara tannin, specifically on melanogenesis, was evaluated in vitro using human epidermal melanocytes (HEM) and B16F10 murine melanoma cells in order to determine the possibility that it may be used as a treatment against hypopigmentation. The melanin content of tara tannin-treated B16F10 cells and the expression level of melanogenesis enzymes and melanosome transport proteins were determined. To elucidate the underlying mechanism of tara tannin’s effect on melanogenesis, DNA microarray analysis was performed. Tara tannin significantly increased melanogenesis in both murine and human pigment cell models by upregulating melanogenesis-associated enzymes’ (tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase) protein and mRNA expression levels, as well as the melanosome transport proteins (myosin Va and RAB27A) expression, both attributed to increased microphthalmia-associated transcription factor (MITF) expression. Global gene expression analysis results revealed the modulation of genes (p≤0.05; fold-change ≥2.0 and ≤−2.0) that are under the transcriptional regulation of MITF and genes relevant for MAPK signaling, metabolic pathways, and cell cycle. Tara tannin has a significant effective melanogenesis-promoting effect, making it a potential therapeutic agent against hypopigmentation disorders. This is the first report on the melanogenesis regulatory effect of tara tannin in vitro.

Diabetes mellitus, especially type 2 (T2DM), is a major public health problem globally. DM is characterized by high levels of glycemia and insulinemia due to impaired insulin secretion and insulin sensitivity of the cells, known as insulin resistance. T2DM causes multiple and severe complications such as nephropathy, neuropathy, and retinopathy causing cell oxidative damages in different internal tissues, particularly the pancreas, heart, adipose tissue, liver, and kidneys. Plant extracts and their bioactive phytochemicals are gaining interest as new therapeutic and preventive alternatives for T2DM and its associated complications. In this regard, isorhamnetin, a plant flavonoid, has long been studied for its potential anti-diabetic effects. This review describes its impact on reducing diabetes-related disorders by decreasing glucose levels, ameliorating the oxidative status, alleviating inflammation, and modulating lipid metabolism and adipocyte differentiation by regulating involved signaling pathways reported in the in vitro and in vivo studies. Additionally, we include a post hoc whole-genome transcriptome analysis of biological activities of isorhamnetin using a stem cell-based tool.

Background Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevacizumab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment. Case presentation A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient’s thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis. Conclusions Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.

Prohydrojasmon has been reported to improve the quality of crops. However, most previous studies have investigated its application on fruits. Here, we evaluated the effect of prohydrojasmon on the growth and total phenolic content, anthocyanin content, and antioxidant activity in komatsuna (Brassica rapa var. periviridis) and lettuce (Lactuca sativa L.). Prohydrojasmon did not show any serious inhibitory effect. Prohydrojasmon applied to komatsuna at a concentration of 0.5 µM significantly increased the total phenolic content and anthocyanin content, and a concentration of 1 µM increased the antioxidant activity. In lettuce, prohydrojasmon at a concentration of 400 µM significantly increased the total phenolic content and anthocyanin content, while a concentration of 0.5 µM significantly increased the antioxidant activity. These results suggest that prohydrojasmon positively affects the phenolic compound and anthocyanin accumulation and antioxidant activity in komatsuna and lettuce without adversely affecting growth.

We examined whether the acetylenic fatty acids 6-octadecynoic acid (6-ODA) and 9-octadecynoic acid (9-ODA) perform as ligands for free fatty acid receptors of medium- and long-chain fatty acids FFAR1 and FFAR4, previously called GPR40 and GPR120, respectively. Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 was increased through FFAR1 but not through FFAR4 expressed in HEK 293 cells, suggesting that 6-ODA and 9-ODA function as an FFAR1 ligand, but not as an FFAR4 ligand. Activation of ERK in FFAR1-expressing HEK293 cells by 6-ODA and 9-ODA peaked at 10 min after stimulation followed by a slow decrease, similar to ERK activation by rosiglitazone, which peaked at 10 min after stimulation and lasted longer. Glucose-dependent production of insulin from MIN6 insulinoma cells was induced by 6-ODA and 9-ODA in an FFAR1-dependent manner. In this process, 6-ODA and 9-ODA stimulated the production of insulin not in the first phase that occurred within 10 min after stimulation but in the second phase. F-actin-remodeling that reflects insulin granule recruiting to the plasma membrane in the second phase of insulin secretion by 6-ODA and 9-ODA suggested that they have an FFAR1-dependent function in insulin secretion from MIN6 cells.

Objectives: To measure phosphorus metabolites in human parotid glands by 31P-MRS using three-dimensional chemical-shift imaging (3D-CSI), and ascertain whether this method can capture changes in adenosine triphosphate (ATP) and phosphocreatine (PCr) levels due to saliva secretion. Study Design: The parotid glands of 20 volunteers were assessed by 31P-MRS using 3D-CSI on 3T MRI. After obtaining a first (baseline) measurement, the participants took vitamin-C tablets and measurements were obtained twice more, in a continuous manner. The peak area ratios of PCr and β-ATP were evaluated. Results: A high proportion of PCr (0.26 ± 0.08) and ATP (α: 0.16 ± 0.06; β: 0.27 ± 0.06; γ: 0.21 ± 0.03) was noted at baseline. A significant decrease in β-ATP was observed between baseline (“pre”; 0.27 ± 0.06) and the first scan after vitamin-C stimulation (“post-1”; 0.19 ± 0.07, p Conclusions: 31P-MRS with 3D-CSI can assess the major phosphorus metabolites in human parotid glands and capture changes in their levels due to saliva secretion. This technique is simple, non-invasive, and provides new information regarding saliva secretion.

The first demonstration of a photothermal heterodyne interferometer (PHI) combined with micro-HPLC (high-performance liquid chromatography) is reported. A semiconductor laser (375 nm) was used for excitation, and the temperature change caused by heat released from photoexcited species was detected with a He-Ne laser (632.8 nm). The temperature-dependent refractive index change of the solvent modified the optical path of the probe beam. The phase difference between two arms of the interferometer, one passing through the heated sample and another as a reference, was sensitively detected with the PHI. The nitro-polycyclic aromatic hydrocarbon and vitamin mixture separated via micro-HPLC was successfully detected with the PHI as well as a UV detector. The detection limit of the PHI for riboflavin in the absorbance units was 77 times better than that of the commercial UV detector. The detection limit of the PHI with a small flow cell (6 nL) was the same as that with a large flow cell (18 nL) for 1-nitropyrene.

The fruits of Rhus tripartita had recently attracted great attention due to its notable therapeutic effects. Their potential effects are attributed to the richness of diverse classes of secondary metabolites. The objective of this research was to access the determination of chemical composition and antioxidant properties of R. tripartita fruit extracts and its partitioned fractions (absolute petroleum ether, 70% aqueous ethanol, absolute ethyl acetate and water). LC–ESI-MS/MS and FTIR–ATR were used to assess the potential of R. tripartita fruits as a source of health-promoting constituents. A total of 38 phenolics, including flavones, flavonols, flavanones, organic acids, hydroxycinnamic acids and hydroxybenzoic acids, 26 of them were reported for the first time in R. tripartita. The main compounds were apigenin7-O-glucoside, apigenin and p-coumaric acid. The FTIR–ATR analysis results revealed the presence of characteristic functional groups such as − OH, C–O, − C = C and C–H of phenolic compounds, carboxylic acids, carbohydrates, lipophilic components and proteins in R. tripartita fruits. Furthermore, the ethyl acetate fraction showed the highest level of phenolic contents and strong antioxidant activities. The present study recommends R. tripartita fruits as source of natural antioxidants which can be used as bioactive ingredient for functional foods and nutraceuticals.

Aim We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. Methods We used 6-, 12- and 24-month (6 M, 12 M and 24 M)-old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real-time polymerase chain reaction, immunoblotting and histological analyses. Results The muscle weight and myocyte cross-sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4-hydroxy-2-nonenal and 3-nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC)-α, peroxisome proliferator-activated receptor gamma coactivator-1β, sirtuin-1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin-proteasome pathway genes muscle ring finger-1 and atrogin-1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated-Akt and -p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P Conclusions These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78-84.

Glaucium flavum (Papaveraceae) is a halophyte which is known for its high importance in phytomedicine and ecology. In this work, phytochemical analysis, as well as antioxidant, antiproliferative and anti-inflammatory effects were investigated for EOH, EA and PE fractions of G. flavum shoots. Results showed that total polyphenol amounts were highest in EOH fraction (158.3 mg GAE/g DR) followed by EA and PE. This latter fraction was rich in flavonoids (128.43 mg CE/g DR), however EA produced more condensed tannins (19.83 mg CE/g DR) than other fractions. In addition, seven molecules (phenolics) have been identified: kaempferol, caffeic acid, catechin hydrate, syringic acid, chlorogenic acid, isoquercitrin, and trans-hydroxycinnamic acid. Concerning antioxidant effects, ethanol fraction was distinguished by a high total antioxidant activity (432.58 mg GAE/g DR), a lower iron reducing power (EC50 = 800 µg/ml), a capacity to inhibit the β-carotene bleaching (IC50 = 48.78 µg/ml), and an important antiradical activity (IC50 = 140 µg/ml). In addition, PE, EA and EOH fractions have strong antiproliferative effect against MCF-7 cells but with superiority of EA fraction (IC50 = 135 µg/ml). EA showed also a high anti-inflammatory effect with an amount of NO which is equal to around 29 and 20 µM/ml NO at 50 and 100 µg/ml, respectively.

Changes of nuclear localization of lineage‐specific genes from a transcriptionally inert to permissive environment are a crucial step in establishing the identity of a cell. Noncoding RNA transcription‐mediated genome folding and activation of target gene expression have been found in a variety of cell types. Noncoding RNA ThymoD (thymocyte differentiation factor) transcription at superenhancers is essential for mouse T‐cell lineage commitment. The cessation of ThymoD transcription abolishes transcription‐mediated demethylation, recruiting looping factors such as the cohesin complex, CCCTC‐binding factor (CTCF), ultimately leading to the phenotype of severe combined immunodeficiency and T‐cell leukemia/lymphoma. In this review, we describe the functional role of RNA polymerase II‐mediated transcription at enhancers and in genome folding. We also highlight the involvement of faulty activation or suppression of enhancer transcription and enhancer‐promoter interaction in cancer development.

Phenolic contents were determined in S. kali leaves, stems, and roots at the beginning, the mid and the end of the vegetative period, as well as the floral bud and open flower at the reproductive stage. Antioxidant and antimicrobial activities were also assessed. Moreover, the major metabolites were identified by HPLC. Results showed a maximum of total phenol contents in the photosynthetic organs, followed by stems and roots. A similar tendency was found for the flavonoids and condensed tannins. Concerning antioxidant analysis, antiradical and Fe-reduced activities were higher in leaves and stems whereas Fe-chelating activity was higher in leaves and roots. Independently of the plant organ, total phenol and flavonoid contents were maximal at the end of the vegetative period whereas tannin content was maximal at the reproductive one. Phenolic contents were related to the organ, the development stage, and their interaction. Concerning the antimicrobial activity, stem extracts were the most efficient against human pathogen strains (Bacteria: Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus, Escherichia coli and Pseudomonas aeruginosa. Fungi: Candida kefyr, C. holmii, C. albicans, C. sake and C. glabrata). Moreover, nine natural products were identified in leaf and stem extracts of S. kali known for their biological activities. As a whole, biological activities of S. kali seem to be strongly related to organs and to the development stage. The phytochemical tests by HPLC demonstrated the presence of nine compounds among them two alkaloids: salsoline and fraxidin. Some molecules are presented in both organs (salsoline, resorcinol, luteolin 7-o-glucoside; and hyperoside). Therefore, endogenous factors greatly account for the biological potential of this medicinal halophyte.

The hair follicle is a complex structure that goes through a cyclic period of growth (anagen), regression (catagen), and rest (telogen) under the regulation of several signaling pathways, including Wnt/ β-catenin, FGF, Shh, and Notch. The Wnt/β-catenin signaling is specifically involved in hair follicle morphogenesis, regeneration, and growth. β-catenin is expressed in the dermal papilla and promotes anagen induction and duration, as well as keratinocyte regulation and differentiation. In this study, we demonstrated the activation of β-catenin by a polyphenolic compound 3,4,5-tri-O-caffeoylquinic acid (TCQA) in mice model and in human dermal papilla cells to promote hair growth cycle. A complete regrowth of the shaved area of C3H mice was observed upon treatment with TCQA. Global gene expression analysis using microarray showed an upregulation in hair growth-associated genes. Moreover, the expression of β-catenin was remarkably upregulated in vivo and in vitro. These findings suggest that β-catenin activation by TCQA promoted the initiation of the anagen phase of the hair cycle.

Six subgroups of sporadic Creutzfeldt-Jakob disease have been identified by distinctive clinicopathologic features, genotype at polymorphic codon 129 [methionine (M)/valine (V)] of the PRNP gene, and type of abnormal prion proteins (type 1 or 2). In addition to the pure subgroups, mixed neuropathologic features and the coexistence of two types of abnormal prion proteins in the same patient also have been reported. Here, we found that a portion of the patients previously diagnosed as MM1 had neuropathologic characteristics of the MM2 thalamic form (ie, neuronal loss of the inferior olivary nucleus of the medulla). Furthermore, coexistence of biochemical features of the MM2 thalamic form also was confirmed in the identified cases. In addition, in transmission experiments using prion protein-humanized mice, the brain material from the identified case showed weak infectivity and generated characteristic abnormal prion proteins in the inoculated mice resembling those after inoculation with brain material of MM2 thalamic form. Taken together, these results show that the co-occurrence of MM1 and MM2 thalamic form is a novel entity of sporadic Creutzfeldt-Jakob disease prion strain co-occurrence. The present study raises the possibility that the co-occurrence of the MM2 thalamic form might have been overlooked so far because of the scarcity of abnormal prion protein accumulation and restricted neuropathology.

A 26-year-old woman with Takayasu's arteritis (TAK) experienced back and neck pain during tocilizumab (TCZ) treatment. The levels of C-reactive protein were normal, and ultrasonography revealed no significant changes. Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) showed signal enhancement in the walls of several arteries. Contrast computed tomography showed arterial inflammation in the same lesion. After increasing the dose of prednisolone and TCZ, all signal enhancements decreased and continued to decrease, as observed on days 76 and 132. Thus, DWIBS may be a novel imaging modality for assessing the disease activity of TAK, particularly during follow-up.

Leptin is an adipocyte-derived hormone that regulates appetite and energy expenditure via the hypothalamus. Since the majority of obese subjects are leptin resistant, leptin sensitizers, rather than leptin itself, are expected to be anti-obesity drugs. Endoplasmic reticulum (ER) stress in the hypothalamus plays a key role in the pathogenesis of leptin resistance. ATP-deficient cells are vulnerable to ER stress and ATP treatment protects cells against ER stress. Thus, we investigated the therapeutic effects of oral 1,3-butanediol (BD) administration, which increases plasma β-hydroxybutyrate and hypothalamic ATP concentrations, in diet induced obese (DIO) mice with leptin resistance. BD treatment effectively decreased food intake and body weight in DIO mice. In contrast, BD treatment had no effect in leptin deficient ob/ob mice. Co-administration experiment demonstrated that BD treatment sensitizes leptin action in both DIO and ob/ob mice. We also demonstrated that BD treatment attenuates ER stress and leptin resistance at the hypothalamus level. This is the first report to confirm the leptin sensitizing effect of BD treatment in leptin resistant DIO mice. The present study provides collateral evidence suggesting that the effect of BD treatment is mediated by the elevation of hypothalamic ATP concentration. Ketone bodies and hypothalamic ATP are the potential target for the treatment of obesity and its complications.

The edible halophyte Nitraria retusa known in traditional medicine purposes was used as a support in this study. The present study investigated the chemical analyses of the general composition of leaf and stem extracts using RP-HPLC. Results showed the richness of these extracts in phenolics especially flavonoids as luteolin-7-O-glucoside, isorhamnetin-3-O-rutinoside, isorhamnetin, quercetin and others. In total, nine compounds were identified for each organ extract. Luteolin-7-O-glucoside, isorhamnetin-3-O-rutinoside and Isorhamnetin are three flavonoids which are common in leaves and stems. Adipogenesis assay was performed to investigate the effect of organs, as well as the three last compounds on the adipocyte differentiation and on the lipid droplets accumulation in 3T3-L1 cells. Based on Oil-Red-O content quantification in 3T3-L1 cells, results showed that each extract of N. retusa at 25, 50, 100, 200 and 400 μg/mL could not inhibit the lipid droplet accumulation compared to untreated cells, in dose dependent manner. However, compounds showed better effect especially with isorhamnetin even with 5μM. Moreover, the effect of extracts and single bioactive components on cell proliferation of 3T3-L1 cells showed that stem extract was more efficient than leaf one. Besides, according to morphological observation, isorhamnetin strongly and significantly affected cell proliferation.

Prohydrojasmon (PDJ) is a synthetic jasmonate derivative that is primarily used as a growth regulator, but its mechanism of action is unclear. In this study, we elucidated the effects of PDJ on phytochemical production in red leaf lettuce. The PDJ treatments promoted the accumulation of phenolic compounds in aerial plant parts. An LC-MS analysis revealed that these accumulated compounds were identified as cyanidin-3-O-glucoside, cyanidin-3-O-(6″-O-malonyl)-glucoside and cyanidin-3-O-(6″-O-malonyl)-glucoside methyl ester. The abundance of these compounds in lettuce extracts increased significantly in response to the PDJ treatment. Additionally, the LC-MS analysis also identified the accumulated phenolic compounds in the extracts of PDJ-treated lettuce, including caffeoyltartaric acid, chlorogenic acid, caffeoylmalic acid, chicoric acid, and dicaffeoylquinic acid. Gene expression analyses indicated the PDJ treatments upregulated the expression of PAL, F3H, and ANS genes in lettuce. These results suggest that PDJ treatments enhance the expression of genes involved in the synthesis of anthocyanins and phenolic compounds, resulting in an increase in the quantities of these compounds, which reportedly have various functions affecting human physiology.

Hair loss is a distressing condition that may not be life-threatening but has an indisputable impact on psychological well-being of an individual. African plant resources have a great potential for use in hair growth promotion. Here, the effect of tara tannin from tara (Caesalpinia spinosa) pods on hair growth promotion was investigated in vitro using hair follicle dermal papilla cells (HFDPC). The noncytotoxic concentration of tara tannin was determined by subjecting HFDPCs to cytotoxicity assay. Then, ATP production was evaluated and quantitative polymerase chain reaction (qPCR) of hair growth promotion molecular markers was performed to determine the promotion effect on hair growth. Results showed that 5 µM tara tannin stimulated HFPDC proliferation, accompanied by an increase in ATP production. Fluorescent staining revealed an increase in s-catenin in tara-tannin-treated cells. QPCR results confirmed that 5 µM tara tannin upregulated the expression of s-catenin (CTNBB), alkaline phosphatase (tissue-nonspecific isozyme) (ALPL), neural cell adhesion molecule 1 (NCAM1), and fibroblast growth factor 1 (FGF1) in HFDPCs. These genes’ expression was upregulated in dermal papilla during the anagen phase of the hair cycle. DNA microarray analysis of tara-tannin-treated pigment cell B16F10 cells (72 h) revealed that cell cycle was one of the most significant signaling pathways modulated. Cell cycle analysis showed that cells were mostly in the G1 phase, consistent with HFDPCs during hair morphogenesis. The results of this study indicated that tara tannin may be used as treatment for alopecia by promoting hair growth.

Background Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant. Methods In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively. Findings Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models. Interpretation Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.

The palladium-catalysed Suzuki–Miyaura cross-coupling reaction of organohalides and organoborons is a reliable method for carbon–carbon bond formation. This reaction involves a base-mediated transmetalation process, but the presence of a base also promotes competitive protodeborylation. Herein, we established a Suzuki–Miyaura cross-coupling reaction via Lewis acid-mediated transmetalation of an organopalladium(II) intermediate with organoborons. Experimental and theoretical investigations indicate that the controlled release of the transmetalation-active intermediate enables base-independent transmetalation under heating conditions and enhances the applicable scope of this process. This system enables us to avoid the addition of a traditional base and, thus, renders substrates with base-sensitive moieties available. Results from this research further expand the overall utility of cross-coupling chemistry.

The GPE− strain is a live attenuated vaccine for classical swine fever (CSF) developed in Japan. In the context of increasing attention for the differentiating infected from vaccinated animals (DIVA) concept, the achievement of CSF eradication with the GPE− proposes it as a preferable backbone for a recombinant CSF marker vaccine. While its infectious cDNA clone, vGPE−, is well characterized, 10 amino acid substitutions were recognized in the genome, compared to the original GPE− vaccine seed. To clarify the GPE− seed availability, this study aimed to generate and characterize a clone possessing the identical amino acid sequence to the GPE− seed. The attempt resulted in the loss of the infectious GPE− seed clone production due to the impaired replication by an amino acid substitution in the viral polymerase NS5B. Accordingly, replication-competent GPE− seed variant clones were produced. Although they were mostly restricted to propagate in the tonsils of pigs, similarly to vGPE−, their type I interferon-inducing capacity was significantly lower than that of vGPE−. Taken together, vGPE− mainly retains ideal properties for the CSF vaccine, compared with the seed variants, and is probably useful in the development of a CSF marker vaccine.

Maslinic acid (MA) is a pentacyclic triterpene abundant in olive peels. MA reportedly increases skeletal muscle mass and strength in older adults, however, the underlying mechanism is unknown. This study aimed to investigate the effects of MA on denervated muscle atrophy and strength and to explore the underlying molecular mechanism. Mice were fed either a control diet or a 0.27% MA diet. One week after intervention, the sciatic nerves of both legs were cut to induce muscle atrophy. Mice were examined 14 days after denervation. MA prevented the denervation-induced reduction in gastrocnemius muscle mass and skeletal muscle strength. Microarray gene expression profiling in gastrocnemius muscle demonstrated several potential mechanisms for muscle maintenance. Gene set enrichment analysis (GSEA) revealed different enriched biological processes, such as myogenesis, PI3/AKT/mTOR signaling, TNFα signaling via NF-κB, and TGF-β signaling in MA-treated mice. In addition, qPCR data showed that MA induced Igf1 expression and suppressed the expressions of Atrogin-1,&nbsp, Murf1 and Tgfb. Altogether, our results suggest the potential of MA as a new therapeutic and preventive dietary ingredient for muscular atrophy and strength.

A comparative study of bioactive lipids extraction from black cumin (Nigella sativa L.) and basil (Ocimum basilicum L.) seeds using conventional petroleum-based solvent and green solvent 2-methyltetrahydrofuran (MeTHF) was performed. MeTHF extraction allowed obtaining the highest oil yield in black cumin (34%). Regarding fatty acids composition, linoleic acid (61%) and α-linolenic (78%) were relevant in black cumin and basil green and conventionally extracted oils, respectively. Besides, MeTHF allowed obtaining higher tocopherols and total phenolics contents in black cumin (400 mg/kg of oil and 12 mg EGA/g oil) and basil (317 mg/kg oil and 5 mg EGA/g oil) compared to hexane-extracted ones. The content of major phenolic compounds in the two seed oils, trans-hydroxycinnamic acid, rosmarinic acid, and thymol was enhanced by MeTHF extraction. Furthermore, MeTHF-extracted oils possess stronger antioxidant activities (radical scavenging, total antioxidant, and β-carotene bleaching activities) and high and similar anti-inflammatory capacity to hexane-extracted oils. In conclusion, the results revealed that MeTHF is efficient to replace hazardous solvents to extract oil from black cumin and basil seeds rich in compounds relevant to the human diet, including essential polyunsaturated fatty acids (n-6 and n-3), tocopherols, and phenolic compounds with improved biological activities.

Nanotechnology is a route of choice that improves administration and efficacy of bioactive compounds. In this study, nanoemulgels were prepared using microfibrillated cellulose from Argania spinosa shell (AS-MFC) and Argan shell (ASE) or Argan press cake extracts (APC) as natural emulsifiers. Oil-in-water (O/W) nanoemulsions were prepared using different natural emulsifiers or synthetic emulsifiers and presented a nano size (d3,2