Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Production of Phenolic Compounds and Antioxidant Activity in Hairy Root Cultures of Salvia plebeia.

Salvia plebeia (Lamiaceae) is a medicinal plant containing diverse bioactive constituents that have biological properties. In this study, we determined the optimal conditions (media and auxin) for the hairy root culture of S. plebeia for the growth and accumulation of phenolic compounds and evaluated its antioxidant activities. Rosmarinic acid and five phenylpropanoids were detected using high-performance liquid chromatography. The hairy roots grown in 1/2 SH medium with 1 mg/L NAA had a high level of rosmarinic acid content. Hairy roots cultured in 1 mg/L NAA had the highest total content of five phenylpropanoids. Compared to wild-type roots grown in the field, hairy roots (NAA 1) expressed similar levels of rosmarinic acid but significantly enhanced phenylpropanoid accumulation. Furthermore, the total phenolic content and total flavonoid content of hairy roots (NAA 1) were 2.22 and 1.73 times higher than those of wild-type roots. In the results of DPPH, ABTS, and reducing power assays, the hairy roots (NAA 1) showed higher free radical scavenging effects and reduction potential than the wild-type roots. These results suggest that S. plebeia hairy roots cultured under optimal conditions, which exhibit enhanced phenolic compound accumulation and antioxidant activity, can potentially be used as sources of antioxidants.

Micromolding-Assisted Production of SERS-Active Microcylinders for Size- and Charge-Selective Molecular Detection.

Surface-enhanced Raman scattering (SERS) is an effective technique for amplifying the Raman signal of molecules by using metal nanostructures. However, these metal surfaces are susceptible to contamination by undesirable adhesives in complex mixtures, typically necessitating a time-consuming and costly sample pretreatment. In order to circumvent this, metal nanoparticles have been uniformly embedded within microgels by using microfluidics. In this work, we introduce a simple, scalable micromolding method for creating SERS-active cylindrical microgels designed to eliminate the need for pretreatment. These microcylinders are created through the simultaneous photoreduction and photo-cross-linking of precursor solutions. These solutions are optimized for consistent, high-intensity Raman signals as well as molecular size and charge selectivity. A sequential micromolding method is employed to design dual-compartment microcylinders, offering additional functionalities such as optical encoding, magnetoresponsiveness, and dual-charge selectivity. These SERS-active microcylinders provide robust Raman signals of small molecules, even in the presence of adhesive proteins, without compromising sensitivity. To demonstrate this capability, we directly detect pyocyanin in saliva and tartrazine in whole milk without any need for sample pretreatment.

Identification of the Plant Family Caryophyllaceae in Korea Using DNA Barcoding.

Caryophyllaceae is a large angiosperm family, with many species being utilized as ornamental or medicinal plants in Korea, in addition to several endangered species that are managed by the government. In this study, we used DNA barcoding for the accurate identification of Korean Caryophyllaceae. A total of 78 taxa (n = 215) were sequenced based on three chloroplast regions (rbcL, matK, and psbA-trnH) and nuclear ribosomal internal transcribed spacers (ITS). In the neighbor-joining tree, a higher accuracy of identification was generally observed when using ITS (>73%) rather than chloroplast regions (<62%). The highest resolution was found for rbcL + ITS (77.6%), although resolution varied according to the genus. Among the genera that included two and more species, five genera (Eremogone, Minuartia, Pseudostellaria, Sagina, and Stellaria) were successfully identified. However, the species of five other genera (Cerastium, Gypsophila, Dianthus, Silene, and Spergularia) showed relatively low resolutions (0-61.1%). In the cases of Cerastium, Dianthus, and Silene, ambiguous taxonomic relationships among unidentified species may have been a factor contributing to such low resolutions. However, in contrast to these results, Gypsophila and Spergularia have been identified well in previous studies. Our findings indicate the need of taxonomic reconsideration in Korea.

Effect of Sinapic Acid on Scopolamine-Induced Learning and Memory Impairment in SD Rats.

The seriousness of the diseases caused by aging have recently gained attention. Alzheimer's disease (AD), a chronic neurodegenerative disease, accounts for 60-80% of senile dementia cases. Continuous research is being conducted on the cause of Alzheimer's disease, and it is believed to include complex factors, such as genetic factors, the accumulation of amyloid beta plaques, a tangle of tau protein, oxidative stress, cholinergic dysfunction, neuroinflammation, and cell death. Sinapic acid is a hydroxycinnamic acid found in plant families, such as oranges, grapefruit, cranberry, mustard seeds, and rapeseeds. It exhibits various biological activities, including anti-inflammatory, anti-oxidant, anti-cancer, and anti-depressant effects. Sinapic acid is an acetylcholine esterase inhibitor that can be applied to the treatment of dementia caused by Alzheimer's disease and Parkinson's disease. However, electrophysiological studies on the effects of sinapic acid on memory and learning must still be conducted. Therefore, it was confirmed that sinapic acid was effective in long-term potentiation (LTP) using organotypic hippocampal segment tissue. In addition, the effect on scopolamine-induced learning and memory impairment was measured by oral administration of sinapic acid 10 mg/kg/day for 14 days, and behavioral experiments related to short-term and long-term spatial memory and avoidance memory were conducted. Sinapic acid increased the activity of the field excitatory postsynaptic potential (fEPSP) in a dose-dependent manner after TBS, and restored fEPSP activity in the CA1 region suppressed by scopolamine. The scopolamine-induced learning and memory impairment group showed lower results than the control group in the Y-maze, Passive avoidance (PA), and Morris water maze (MWM) experiments. Sinapic acid improved avoidance memory, short and long-term spatial recognition learning, and memory. In addition, sinapic acid weakened the inhibition of the brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and the activation of prostaglandin-endoperoxide synthase 2 (COX-2) and interleukin 1 beta (IL-1ß) induced by scopolamine in the hippocampus. These results show that sinapic acid is effective in restoring LTP and cognitive impairment induced by the cholinergic receptor blockade. Moreover, it showed the effect of alleviating the reduction in scopolamine-induced BDNF and TrkB, and alleviated neuroinflammatory effects by inhibiting the increase in COX-2 and IL-1ß. Therefore, we showed that sinapic acid has potential as a treatment for neurodegenerative cognitive impairment.

Comparison of Outcomes of Multi-Level Anterior, Oblique, Transforaminal Lumbar Interbody Fusion Surgery : Impact on Global Sagittal Alignment.

OBJECTIVE: To compare the outcomes of anterior lumbar interbody fusion (ALIF), oblique lumbar interbody fusion (OLIF), and transforaminal lumbar interbody fusion (TLIF) in terms of global sagittal alignment. METHODS: From January 2007 to December 2019, 141 adult patients who underwent multilevel interbody fusion for lumbar degenerative disorders were enrolled. Regarding the approach, patients were divided into the ALIF (n=23), OLIF (n=60), and TLIF (n=58) groups. Outcomes, including local radiographic parameters and global sagittal alignment, were then compared between the treatment groups. RESULTS: Regarding local radiographic parameters, ALIF and OLIF were superior to TLIF in terms of the change in the anterior disc height (7.6±4.5 mm vs. 6.9±3.2 mm vs. 4.7±2.9 mm, p<0.001), disc angle (-10.0°±6.3° vs. -9.2°±5.2° vs. -5.1°±5.1°, p<0.001), and fused segment lordosis (-14.5°±11.3° vs. -13.8°±7.5° vs. -7.4°±9.1°, p<0.001). However, regarding global sagittal alignment, postoperative lumbar lordosis (-42.5°±9.6° vs. -44.4°±11.6° vs. -40.6°±12.3°, p=0.210), pelvic incidence-lumbar lordosis mismatch (7.9°±11.3° vs. 6.7°±11.6° vs. 11.5°±13.0°, p=0.089), and the sagittal vertical axis (24.3±28.5 mm vs. 24.5±34.0 mm vs. 25.2±36.6 mm, p=0.990) did not differ between the groups. CONCLUSION: Although the anterior approaches were superior in terms of local radiographic parameters, TLIF achieved adequate global sagittal alignment, comparable to the anterior approaches.

Effects of various Agrobacterium rhizogenes strains on hairy root induction and analyses of primary and secondary metabolites in Ocimum basilicum.

The hairy root (HR) culture system is an excellent alternative strategy to the whole plant system for producing valuable compounds. However, selection of suitable Agrobacterium strain for the successful induction of HR is an essential step for enhanced production of beneficial secondary metabolites. In this study, we examined the transformation efficiency of various A. rhizogenes strains (ATCC 13333, ATCC 15834, A4, R1000, R1200, and R1601) for transgenic HRs induction in Ocimum basilicum. Among the tested strains, the R1601 was found to be one of the most promising strain for mass production of HR in terms of transformation efficiency (94%) and the number and length of HR (8.4 ± 0.52 and 1.68 ± 0.14 cm). The HR induced by the same strain exhibited highest levels of rosmarinic acid level (62.05 ± 4.94 µg/g DW) and total phenolic content (62.3 ± 4.95 µg/g DW). A total of 55 metabolites were identified using high-performance liquid chromatography (HPLC) and gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). The PCA and PLS-DA plot of the identified metabolites showed that HR induced by A4 and ATCC 15834 displayed variation in primary and secondary metabolite contents. Analysis of the metabolic pathway identified a total of 56 pathways, among which 35 were found to be impacted. A heat map and hierarchical clustering analysis indicated that HR induced by different Agrobacterium strains exhibited differential metabolites profiles. In conclusion, Agrobacterium strains R1601 is one of the best and most promising strains for inducing mass HR production and enhanced levels of secondary metabolites in O. basilicum.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials. Real-time imaging and molecular dynamics simulations demonstrate the deswelling of RGD-bearing microgels via visible-light-mediated trans-azobenzene formation. Near-infrared light can induce in situ swelling of RGD-bearing microgels to increase RGD availability and trigger release of loaded interleukin-4, which facilitates the adhesion structure assembly linked with pro-regenerative polarization of host macrophages. In contrast, visible light can induce deswelling of RGD-bearing microgels to decrease RGD availability that suppresses macrophage adhesion that yields pro-inflammatory polarization. These microgels exhibit high stability and non-toxicity. Versatile use of ligands and protein delivery can offer cytocompatible and photoswitchable manipulability of diverse host cells.

Herbal Medicines for Post-Acute Sequelae (Fatigue or Cognitive Dysfunction) of SARS-CoV-2 Infection: A Phase 2 Pilot Clinical Study Protocol.

Long-term sequelae refer to persistent symptoms or signs for >6 months after SARS-CoV-2 infection. The most common symptoms of sequelae are fatigue and neuropsychiatric symptoms (concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression). However, approved treatments have not been fully established. Herbal medicines are administered for 12 weeks to patients who continuously complain of fatigue or cognitive dysfunction for >4 weeks that only occurred after COVID-19 diagnoses. Based on the Korean Medicine syndrome differentiation diagnosis, patients with fatigue will be administered Bojungikgi-tang or Kyungok-go, whereas those with cognitive dysfunction will be administered Cheonwangbosim-dan. Results could support evidence that herbal medicines may mitigate fatigue and cognitive dysfunction caused by COVID-19. Furthermore, by investigating the effects of herbal medicines on changes in metabolite and immune response due to COVID-19, which may be responsible for sequelae, the potential of herbal medicines as one of the therapeutic interventions for post-acute sequelae of SARS-CoV-2 infection can be evaluated. Therefore, the effects of herbal medicine on fatigue and cognitive dysfunction sequelae due to COVID-19 will be elucidated in this study to provide an insight into the preparation of medical management for the post-acute sequelae of SARS-CoV-2 infection.

Excited-State Intramolecular Hydrogen Transfer of Compact Molecules Controls Amyloid Aggregation Profiles.

Developing chemical methodologies to directly modify harmful biomolecules affords the mitigation of their toxicity by persistent changes in their properties and structures. Here we report compact photosensitizers composed of the anthraquinone (AQ) backbone that undergo excited-state intramolecular hydrogen transfer, effectively oxidize amyloidogenic peptides, and, subsequently, alter their aggregation pathways. Density functional theory calculations showed that the appropriate position of the hydroxyl groups in the AQ backbone and the consequent intramolecular hydrogen transfer can facilitate the energy transfer to triplet oxygen. Biochemical and biophysical investigations confirmed that these photoactive chemical reagents can oxidatively vary both metal-free amyloid-ß (Aß) and metal-bound Aß, thereby redirecting their on-pathway aggregation into off-pathway as well as disassembling their preformed aggregates. Moreover, the in vivo histochemical analysis of Aß species produced upon photoactivation of the most promising candidate demonstrated that they do not aggregate into oligomeric or fibrillar aggregates in the brain. Overall, our combined computational and experimental studies validate a light-based approach for designing small molecules, with minimum structural complexity, as chemical reagents targeting and controlling amyloidogenic peptides associated with neurodegenerative disorders.

Optimization of Fermentation Conditions of Artemisia capillaris for Enhanced Acetylcholinesterase and Butyrylcholinesterase.

In this study, the fermentation of Artemisia capillaris by probiotic Leuconostoc mesenteroides MKJW (MKJW) was optimized to increase the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory and antioxidant activities using the response surface method (RSM). The independent variables were the contents of A. capillaris, Gryllus bimaculatus, and yeast extract, while the dependent variables were AChE inhibitory activity, BuChE inhibitory activity, and antioxidant activities such as FRAP, reducing power, and DPPH radical scavenging ability. Seventeen experimental runs were designed with RSM and analyzed after fermentation with MKJW. Quadratic models were used to analyze the inhibition of AChE and BuChE, and a linear model was used to analyze the FRAP. The three models were significantly appropriate (p < 0.0001). The highest optimal condition of the AChE inhibitory activity was derived by a multiple regression equation. When the optimum fermentation conditions were A. capillaris 6.75%, G. bimaculatus 0.18%, and yeast extract 1.27%, 91.1% was reached for AChE inhibitory, 74.0% for BuChE inhibitory, and 34.1 mM FeSO4 for FRAP. The predicted dependent variables were not significantly different from the experimental values (p > 0.05). In conclusion, the A. capillaris fermented by MKJW might be used as a natural antidementia improving agent with AChE inhibitory, BuChE inhibitory, and antioxidant activities.

Effect of Dexmedetomidine Compared to Remifentanil During Bariatric Surgery on Postoperative Nausea and Vomiting: a Retrospective Study.

PURPOSE: Postoperative nausea and vomiting (PONV) occurs frequently after bariatric surgery and is a major cause of adverse outcomes. This retrospective study investigated whether opioid-restricted total intravenous anesthesia using dexmedetomidine as a substitute for remifentanil can reduce PONV in bariatric surgery. MATERIALS AND METHODS: The electronic medical records of adult patients who underwent laparoscopic bariatric surgery between January and December 2019 were reviewed. The patients were divided into two groups according to the agents used for anesthesia: Group D, propofol and dexmedetomidine; Group R, propofol and remifentanil. RESULTS: A total of 134 patients were included in the analyses. The frequency of postoperative nausea was significantly lower in Group D than that in Group R until 2 h after discharge from the postanesthesia care unit (PACU) (P = 0.005 in the PACU, P = 0.010 at 2 h after PACU discharge) but failed to significantly reduce the overall high incidence rates of 60.5% and 65.5%, respectively (P = 0.592). Postoperative pain score was significantly lower in Group D until 6 h after PACU discharge. The rates of rescue antiemetic and analgesic agent administration in the PACU were significantly lower in Group D than those in Group R. CONCLUSION: Opioid-restricted total intravenous anesthesia using dexmedetomidine reduces postoperative nausea, pain score, antiemetic, and analgesic requirements in the immediate postoperative period after bariatric surgery.

Conformational and functional changes of the native neuropeptide somatostatin occur in the presence of copper and amyloid-ß.

The progression of neurodegenerative disorders can lead to impaired neurotransmission; however, the role of pathogenic factors associated with these diseases and their impact on the structures and functions of neurotransmitters have not been clearly established. Here we report the discovery that conformational and functional changes of a native neuropeptide, somatostatin (SST), occur in the presence of copper ions, metal-free amyloid-ß (Aß) and metal-bound Aß (metal-Aß) found as pathological factors in the brains of patients with Alzheimer's disease. These pathological elements induce the self-assembly of SST and, consequently, prevent it from binding to the receptor. In the reverse direction, SST notably modifies the aggregation profiles of Aß species in the presence of metal ions, attenuating their cytotoxicity and interactions with cell membranes. Our work demonstrates a loss of normal function of SST as a neurotransmitter and a gain of its modulative function against metal-Aß under pathological conditions.

Melatonin reduces the endoplasmic reticulum stress and polyubiquitinated protein accumulation induced by repeated anesthesia exposure in Caenorhabditis elegans.

Endoplasmic reticulum (ER) stress has been linked to anesthesia-induced neurotoxicity, but melatonin seems to play a protective role against ER stress. Synchronized Caenorhabditis elegans were exposed to isoflurane during the developmental period; melatonin treatment was used to evaluate its role in preventing the defective unfolded protein response (UPR) and ER-associated protein degradation (ERAD). The induced expression of hsp-4::GFP by isoflurane was attenuated in the isoflurane-melatonin group. Isoflurane upregulated the expression of ire-1, whereas melatonin did not induce ire-1 expression in C. elegans even after isoflurane exposure. With luzindole treatment, the effect of melatonin on the level of ire-1 was significantly attenuated. The reduced expression of sel-1, sel-11, cdc-48.1, and cdc-48.2 due to isoflurane was restored by melatonin, although not up to the level of the control group. The amount of polyubiquitinated proteins was increased in the isoflurane group; however, melatonin suppressed its accumulation, which was significantly inhibited by a proteasome inhibitor, MG132. The chemotaxis index of the isoflurane-melatonin group was improved compared with the isoflurane group. Melatonin may be a potential preventive molecule against defective UPR and ERAD caused by repeated anesthesia exposure. The ire-1 branch of the UPR and ERAD pathways can be the target of melatonin to reduce anesthesia-induced ER stress.

Wrinkle reduction using a Sasang constitutional medicine-based topical herbal cream in So-eum subjects: A split-face randomized double-blind placebo-controlled study.

BACKGROUND: Skin aging is caused by exogenous and endogenous factors and is commonly manifested as wrinkling, sagging, and looseness of the skin. The herbal extract including Zingiber officinale Roscoe, Atractylodes chinensis (Bunge) Kodiz, Curcuma longa L., and Cinnamomum cassia (L.) J.Presl (ZACC extract), is widely used for So-eum (SE) Sasang constitutional type individuals. This study aimed to examine the protective effects of the ZACC extract against skin aging in 21 SE type subjects. METHODS: The safety and clinical efficacy of herbal cream were evaluated after application on human skin in a split-face randomized, double-blind, placebo-controlled study. The Sasang Constitution Analysis Tool (SCAT) was used to select 21 SE type subjects, who applied herbal cream and placebo cream for 12 weeks. Visual assessment, wrinkle parameters, questionnaires, and skin safety were evaluated. RESULTS: The visual assessment score was decreased by using of the herbal cream, but there were no significant differences between groups. Among the wrinkle parameters, R1 (skin roughness) and R4 (smoothness depth) values were significantly improved after the application of the herbal cream compared to those observed after application of the placebo cream for 12 weeks. No significant differences were observed in evaluation of the product efficacy and usability by questionnaires. There were no adverse dermatologic reactions in the SE type subjects during the evaluation period. CONCLUSION: The ZACC herbal cream may be used to prevent or slow skin aging, including wrinkle formation, in SE type individuals.

5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older patients undergoing orthopedic lower limb surgery.

BACKGROUND: Delirium is an important postoperative complication. Recent research suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists may have clinical effect in the treatment and prevention of delirium. We investigated the association between 5-HT3 receptor antagonists and the occurrence of postoperative delirium (POD). METHODS: Retrospectively, the electronic medical records were reviewed in patients aged ≥ 65 years who underwent orthopedic lower limb surgery under regional anesthesia (spinal or combined spinal-epidural anesthesia) and administered intravenous 0.075 mg palonosetron or 0.3 mg ramosetron prior to the end of surgery between July 2012 and September 2015. POD incidence and anesthesia-, surgery-, and patient-related factors were evaluated. To investigate the association between 5-HT3 receptor antagonists and the occurrence of POD, multivariable logistic regression analysis was performed. RESULTS: Of the 855 patients included, 710 (83%) were administered 5-HT3 receptor antagonists. POD was confirmed in 46 (5.4%) patients. 5-HT3 receptor antagonists reduced the POD incidence by 63% (odds ratio [OR] 0.37; 95% confidence interval [CI], 0.15-0.94; P = 0.04). Moreover, the POD incidence decreased by 72% (OR 0.28, 95% CI 0.10-0.77, P = 0.01) when palonosetron was administered. Other identified risk factors for POD were emergency surgery, older age, hip surgery, lower body mass index, and intraoperative propofol sedation. CONCLUSION: 5-HT3 receptor antagonists may be related with a significantly reduced risk for POD in older patients undergoing orthopedic lower limb surgery. Notably, palonosetron was more effective for POD prevention.

Skimmed milk fermented by lactic acid bacteria inhibits adipogenesis in 3T3-L1 pre-adipocytes by downregulating PPARγ via TNF-α induction in vitro.

The murine 3T3-L1 pre-adipocyte cell line is widely used as an in vitro model for adipogenesis because of its similarities to primary fat cells. The aim of this study was to investigate the intracellular mechanisms by which skimmed milk fermented by two lactic acid bacteria (LAB), Enterococcus faecalis and Lactobacillus plantarum, inhibited the differentiation of 3T3-L1 pre-adipocytes. Skimmed milk fermented by both LAB, but not non-fermented skimmed milk, significantly reduced the accumulation of lipid droplets and cellular triglycerides in a concentration-dependent manner. The mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ) were markedly inhibited in the presence of skimmed milk fermented by both LAB. Furthermore, the skimmed milk fermented by both LAB decreased the mRNA and protein expressions of PPARγ-targeting genes, lipoprotein lipase and adipocyte fatty acid-binding protein. Under the same circumstances, resistin mRNA expression was downregulated, but not leptin mRNA expression. In contrast, skimmed milk fermented by both LAB significantly upregulated tumor necrosis factor-α (TNF-α). These results suggest that LAB-fermented skimmed milk inhibits adipogenesis by inhibiting a master transcription factor PPARγ via the upregulation of the proinflammatory cytokine TNF-α in 3T3-L1 cells.

The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea.

BACKGROUND: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). METHODS: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. RESULTS: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38-2.78; class II, OR: 3.33, 95% CI: 1.77-6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31-2.95; class II, OR: 2.96, 95% CI: 1.51-5.78). CONCLUSION: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

Erratum: Clustering the Clinical Course of Chronic Urticaria Using a Longitudinal Database: Effects on Urticaria Remission.

This corrects the article on p. 390 in vol. 13, PMID: 33733635.

The role of neuropeptide somatostatin in the brain and its application in treating neurological disorders.

Somatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer's disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer's disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.