Exploring the challenges of taiwanese nurses in the COVID-19 post-pandemic era.

In the wake of the COVID-19 pandemic, the fluctuating nurse resignation rates highlighted an understudied area in healthcare: post-pandemic challenges in clinical settings. This study, conducted from May to November 2023, employed a qualitative inquiry using focus groups to delve into these challenges. Six focus group sessions, involving 33 nurse participants recruited through snowball sampling from various hospital settings were conducted to explore their clinical experiences during and after the pandemic. Thematic analysis revealed two primary themes: the 'Invisibility of Nurses' within the healthcare system and the 'Moral Duty of Nursing Practice'. These findings illuminate a tension between the overlooked role of nurses and their ethical obligations, underscoring a critical need for policy reassessment. The study advocates for systemic changes, particularly in the undervaluation of the nursing profession and the National Health Insurance system, to address the poor working environment and mitigate long-term nursing shortages. This research deepens understanding of post-pandemic nursing workforce challenges in Taiwan, highlighting the need for policy evolution to enhance recognition and support for the nursing industry. It is suggested to provide tangible compensation to acknowledge nurses' daily care and health education for patients. A healthier working environment can be enhanced by collaborative efforts between healthcare institutions and nurses.

Potato protein hydrolysate inhibits RANKL-induced osteoclast development by inhibiting osteoclastogenic genes via the NF-κB/MAPKs signaling pathways.

In recent times, there has been growing attention towards exploring the nutritional and functional aspects of potato protein, along with its diverse applications. In the present study, we examined the anti-osteoclast properties of potato protein hydrolysate (PP902) in vitro. Murine macrophages (RAW264.7) were differentiated into osteoclasts by receptor activator of nuclear factor-κB ligand (RANKL), and PP902 was examined for its inhibitory effect. Initially, treatment with PP902 was found to significantly prevent RANKL-induced morphological changes in macrophage cells, as determined by tartrate-resistant acid phosphatase (TRAP) staining analysis. This notion was further supported by F-actin analysis using a confocal microscope. Furthermore, PP902 treatment effectively and dose-dependently down-regulated the expression of RANKL-induced osteoclastogenic marker genes, including TRAP, CTR, RANK, NFATc1, OC-STAMP, and c-Fos. These inhibitory effects were associated with suppressing NF-κB transcriptional activation and subsequent reduced nuclear translocation. The decrease in NF-κB activity resulted from reduced activation of its upstream kinases, including I-κBα and IKKα. Moreover, PP902 significantly inhibited RANKL-induced p38MAPK and ERK1/2 activities. Nevertheless, PP902 treatment prevents RANKL-induced intracellular reactive oxygen species generation via increased HO-1 activity. The combined antioxidant and anti-inflammatory effects of PP902 resulted in significant suppression of osteoclastogenesis, suggesting its potential as an adjuvant therapy for osteoclast-related diseases.

Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks.

The interaction of the tumor necrosis factor receptor (TNFR) family member CD27 on naive CD8+ T (Tn) cells with homotrimeric CD70 on antigen-presenting cells (APCs) is necessary for T cell memory fate determination. Here, we examined CD27 signaling during Tn cell activation and differentiation. In conjunction with T cell receptor (TCR) stimulation, ligation of CD27 by a synthetic trimeric CD70 ligand triggered CD27 internalization and degradation, suggesting active regulation of this signaling axis. Internalized CD27 recruited the signaling adaptor TRAF2 and the phosphatase SHP-1, thereby modulating TCR and CD28 signals. CD27-mediated modulation of TCR signals promoted transcription factor circuits that induced memory rather than effector associated gene programs, which are induced by CD28 costimulation. CD27-costimulated chimeric antigen receptor (CAR)-engineered T cells exhibited improved tumor control compared with CD28-costimulated CAR-T cells. Thus, CD27 signaling during Tn cell activation promotes memory properties with relevance to T cell immunotherapy.

Thiamet G as a Potential Treatment for Polycystic Kidney Disease.

BACKGROUND/AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder primarily caused by mutations in Pkd1 (PC1), which account for the majority of ADPKD cases. These mutations contribute to the formation of cysts in the kidneys and other organs, ultimately leading to renal failure. Unfortunately, there are currently no available preventive treatments for this disease. MATERIALS AND METHODS: In this study, we utilized Pkd1-knockdown mice and cells to investigate the potential involvement of O-GlcNAcylation in the progression of PKD. Additionally, we examined the effects of thiamet G, an inhibitor of O-GlcNAcase (OGA), on PKD mice. RESULTS: Our findings indicate that both O-GlcNAcylation and OGT (O-GlcNAc transferase) were downregulated in the renal tissues of Pkd1-silenced mice. Furthermore, O-GlcNAcylation was shown to regulate the stability and function of the C-terminal cytoplasmic tail (CTT) of PC1. Treatment of PKD mice with thiamet G resulted in a reduction of renal cytogenesis in these animals. CONCLUSION: These results highlight the unique role of O-GlcNAcylation in the development of cyst formation in PKD and propose it as a potential therapeutic target for the treatment of PKD.

22q11.2 Deletion Syndrome in Taiwan: Clinical Presentation and Immune System Status of Patients.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.

Nor-24-homoscalaranes, Neutrophilic Inflammatory Mediators from the Marine Sponge Lendenfeldia sp.

The marine sponge Lendenfeldia sp., collected from the Southern waters of Taiwan, was subjected to chemical composition screening, resulting in the isolation of four new 24-homoscalarane compounds, namely lendenfeldaranes R-U (1-4). The structures and relative stereochemistry of the new metabolites 1-4 were assigned based on NMR studies. The absolute configurations of compounds 1-4 were determined by comparing the calculated and experimental values of specific optical rotation. The antioxidant and anti-inflammatory activities of the isolated compounds were assayed using superoxide anion generation and elastase release assays. These assays are used to determine neutrophilic inflammatory responses of respiratory burst and degranulation. Compounds 2 and 4 inhibited superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB) with IC50: 3.98-4.46 µM. Compounds 2 and 4 inhibited fMLP/CB-induced elastase release, with IC50 values ranging from 4.73 to 5.24 µM. These findings suggested that these new 24-homoscalarane compounds possess unique structures and potential anti-inflammatory activity.

Unlocking the Potential of Octocoral-Derived Secondary Metabolites against Neutrophilic Inflammatory Response.

Inflammation is a critical defense mechanism that is utilized by the body to protect itself against pathogens and other noxious invaders. However, if the inflammatory response becomes exaggerated or uncontrollable, its original protective role is not only demolished but it also becomes detrimental to the affected tissues or even to the entire body. Thus, regulating the inflammatory process is crucial to ensure that it is resolved promptly to prevent any subsequent damage. The role of neutrophils in inflammation has been highlighted in recent decades by a plethora of studies focusing on neutrophilic inflammatory diseases as well as the mechanisms to regulate the activity of neutrophils during the overwhelmed inflammatory process. As natural products have demonstrated promising effects in a wide range of pharmacological activities, they have been investigated for the discovery of new anti-inflammatory therapeutics to overcome the drawbacks of current synthetic agents. Octocorals have attracted scientists as a plentiful source of novel and intriguing marine scaffolds that exhibit many pharmacological activities, including anti-inflammatory effects. In this review, we aim to provide a summary of the neutrophilic anti-inflammatory properties of these marine organisms that were demonstrated in 46 studies from 1995 to the present (April 2023). We hope the present work offers a comprehensive overview of the anti-inflammatory potential of octocorals and encourages researchers to identify promising leads among numerous compounds isolated from octocorals over the past few decades to be further developed into anti-inflammatory therapeutic agents.

Principle active metabolites of Pinus morrisonicola Hayata synergistically inhibit cell proliferation and autophagy to elevate apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC), a common primary tumor of liver is a leading cause of cancer-associated deaths. Improving cellular apoptosis and enhancing autophagic clearance is been considered to improve treatment outcomes of HCC. Polyphenols from Pinus morrisonicola (Hayata) have shown various physiological and therapeutic benefits and the flavonoid chrysin is been known for their anticancer effects. However, the main bioactive principle and the mechanism underlying the antitumor activity of pine needle extract are not clear yet. In this study, the effects of ethanol extract from pine needle on HCC cells were determined. The results show that when compared with administration of chrysin alone, a fraction containing pinocembrin, chrysin, and tiliroside significantly reduced autophagy and increased apoptosis. The results also correlated with decrease in cell cycle regulators and the autophagic proteins like LC3-II. Collectively, the results imply the fraction containing pinocembrin, chrysin, and tiliroside as an ideal complementary medicine for an effective antitumor activity.

A prolonged stress rat model recapitulates some PTSD-like changes in sleep and neuronal connectivity.

Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors. Behavioral and neural changes following MPS conveyed longitudinal PTSD-like effects in rats for 6 weeks. Extended fear memory was estimated through fear retrieval induced-freezing behavior and increased long-term serum corticosterone concentrations after MPS manipulation. Additionally, memory retrieval and behavioral anxiety tasks continued enhancing theta oscillation activity in the prefrontal cortex-basal lateral amygdala-ventral hippocampus pathway for an extended period. Moreover, MPS and remote fear retrieval stimuli disrupted sleep-wake activities to consolidate fear memory. Our prolonged fear memory, neuronal connectivity, anxiety, and sleep alteration results demonstrated integrated chronic PTSD symptoms in an MPS-induced rodent model.

Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective.

Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.

Quercus coccinea Münchh leaves polyphenols: Appraisal acute lung injury induced by lipopolysaccharide in mice.

Genus Quercus is a well-known source for its polyphenolic content and important biological activity. Plants belonging to the Quercus genus were traditionally used in asthma, inflammatory diseases, wound healing, acute diarrhea, and hemorrhoid. Our work intended to study the polyphenolic profile of the Q. coccinea (QC) leaves and to assess the protective activity of its 80% aqueous methanol extract (AME) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Together, the potential molecular mechanism was investigated. Nineteen polyphenolic compounds (1-18), including tannins, flavone, and flavonol glycosides. Phenolic acids and aglycones were purified and identified from the AME of QC leaves. Treatment with AME of QC showed an anti-inflammatory effect evidenced by a remarkable decline in the count of white blood cells and neutrophils which was in harmony with decreasing the levels of high mobility group box-1, nuclear factor kappa B, tumor necrosis factor-α, and interleukin 1 beta. In addition, the antioxidant activity of QC was documented through the significant reduction in malondialdehyde level and elevation of reduced glutathione level and superoxide dismutase activity. Furthermore, the mechanism involved in the pulmonary protective effect of QC involved the downregulation of the TLR4/MyD88 pathway. The AME of QC showed a protective effect against LPS-induced ALI through the powerful anti-inflammatory and antioxidant activities which are linked to its abundancy with polyphenols.

Chemometric-guided chemical marker selection: A case study of the heat-clearing herb Scrophularia ningpoensis.

The selection of medicinal plants' chemical markers focuses on bioactivity as the primary goal, followed by the nature of secondary metabolites, their stability, and availability. However, herbal medicines are valued for their complex and holistic pharmacological effects. A correct chemical marker can be carefully selected by a systematic clarification of their chemical-biological relationships. In the current study, the multi-informative molecular networking (MIMN) approach was employed to construct the anti-inflammatory metabolomic pattern of a heat-clearing herb, Scrophularia ningpoensis Hemsl. (S. ningpoensis). The MIMN molecular families characterized by cinnamic acid glycosides showed a higher bioactivity score compared with the other two major chemical classes (iridoid glycosides and iridoid-cinnamic acid glycosides). The Global Natural Product Social Molecular Networking (GNPS) and Reaxys database were used to assist in the putative annotation of eighteen metabolites from the bioactive and non-bioactive molecular families. The anti-inflammatory validation step was based on the detection of reactive oxygen species (ROS) generation by activated human neutrophils. All compounds from the bioactive MIMN molecular families dose-dependently inhibited the total ROS generation promoted by fMLF (IC50: 0.04-0.42 µM), while the compounds from non-bioactive MIMN clusters did not show any significant anti-inflammatory effect. The ROS-dependent anti-inflammatory activity of these cinnamic acid glycosides was attributed to their oxygen radical scavenging ability. The most abundant cinnamic acid glycoside, angoroside C (IC50: 0.34 µM) was suggested to be selected as a chemical marker for S. ningpoensis. In this study, the MIMN platform was applied to assist in the chemical marker selection of S. ningpoensis. The correct selection of markers will aid in the compilation and revision of herbal monographs and pharmacopeias resulting in the precise analysis and classification of medicinal plants on a scientific basis.

Essential Oil from Glossogyne tenuifolia Inhibits Lipopolysaccharide-Induced Inflammation-Associated Genes in Macro-Phage Cells via Suppression of NF-κB Signaling Pathway.

Glossogyne tenuifolia Cassini (Hsiang-Ju in Chinese) is a perennial herb native to Taiwan. It was used in traditional Chinese medicine (TCM) as an antipyretic, anti-inflammatory, and hepatoprotective agent. Recent studies have shown that extracts of G. tenuifolia possess various bioactivities, including anti-oxidant, anti-inflammatory, immunomodulation, and anti-cancer properties. However, the pharmacological activities of G. tenuifolia essential oils have not been studied. In this study, we extracted essential oil from air-dried G. tenuifolia plants, then investigated the anti-inflammatory potential of G. tenuifolia essential oil (GTEO) on lipopolysaccharide (LPS)-induced inflammation in murine macrophage cells (RAW 264.7) in vitro. Treatment with GTEO (25, 50, and 100 µg/mL) significantly as well as dose-dependently inhibited LPS-induced pro-inflammatory molecules, such as nitric oxide (NO) and prostaglandin E2 (PGE2) production, without causing cytotoxicity. Q-PCR and immunoblotting analysis revealed that the inhibition of NO and PGE2 was caused by downregulation of their corresponding mediator genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), respectively. Immunofluorescence and luciferase reporter assays revealed that the inhibition of iNOS and COX-2 genes by GTEO was associated with the suppression of nuclear export and transcriptional activation of the redox-sensitive transcription factor, nuclear factor -κB (NF-κB). In addition, GTEO treatment significantly inhibited phosphorylation and proteosomal degradation of the inhibitor of NF-κB (I-κBα), an endogenous repressor of NF-κB. Moreover, treatment with GTEO significantly blocked the LPS-mediated activation of inhibitory κB kinase α (IKKα), an upstream kinase of the I-κBα. Furthermore, p-cymene, ß-myrcene, ß-cedrene, cis-ß-ocimene, α-pinene, and D-limonene were represented as major components of GTEO. We found that treatment with p-cymene, α-pinene, and D-limonene were significantly inhibiting LPS-induced NO production in RAW 264.7 cells. Taken together, these results strongly suggest that GTEO inhibits inflammation through the downregulation of NF-κB-mediated inflammatory genes and pro-inflammatory molecules in macrophage cells.

Widespread sex ratio polymorphism in Caenorhabditis nematodes.

Although equal sex ratio is ubiquitous and represents an equilibrium in evolutionary theory, biased sex ratios are predicted for certain local conditions. Cases of sex ratio bias have been mostly reported for single species, but little is known about its evolution above the species level. Here, we surveyed progeny sex ratios in 23 species of the nematode genus Caenorhabditis, including 19 for which we tested multiple strains. For the species with multiple strains, five species had female-biased and two had non-biased sex ratios in all strains, respectively. The other 12 species showed polymorphic sex ratios across strains. Female-biased sex ratios could be due to sperm competition whereby X-bearing sperm outcompete nullo-X sperm during fertilization. In this model, when sperm are limited allowing all sperm to be used, sex ratios are expected to be equal. However, in assays limiting mating to a few hours, most strains showed similarly biased sex ratios compared with unlimited mating experiments, except that one C. becei strain showed significantly reduced female bias compared with unlimited mating. Our study shows frequent polymorphism in sex ratios within Caenorhabditis species and that sperm competition alone cannot explain the sex ratio bias.

UHPLC-MS profiles and antidiarrheal activity of Quercus coccinea münchh. and Quercus robur L. employing in vivo technique.

Introduction: Quercus L. genus (Oak) belongs to the family Fagaceae and their galls are used commercially in leather tanning, dyeing, and ink preparation. Several Quercus species were traditionally used to manage wound healing, acute diarrhea, hemorrhoid, and inflammatory diseases. The present study aims to investigate the phenolic content of the 80% aqueous methanol extract (AME) of Q. coccinea and Q. robur leaves as well as to assess their anti-diarrheal activity. Methods: Polyphenolic content of Q. coccinea and Q. robur AME were investigated using UHPLC/MS. The antidiarrheal potential of the obtained extracts was evaluated by conducting a castor oil-induced diarrhea in-vivo model. Result and Discussion: Twenty-five and twenty-six polyphenolic compounds were tentatively identified in Q. coccinea and Q. robur AME, respectively. The identified compounds are related to quercetin, kaempferol, isorhamnetin, and apigenin glycosides and their aglycones. In addition, hydrolyzable tannins, phenolic acid, phenyl propanoides derivatives, and cucurbitacin F were also identified in both species AME of Q. coccinea (250, 500, and 1000 mg/kg) exhibited a significant prolongation in the onset of diarrhea by 17.7 %, 42.6%, and 79.7% respectively while AME of Q. robur at the same doses significantly prolonged the onset of diarrhea by 38.6%, 77.3%, and 2.4 folds respectively as compared to the control. Moreover, the percentage of diarrheal inhibition of Q. coccinea was 23.8%, 28.57%, and 42,86% respectively, and for Q. robur 33.34%, 47.3%, and 57.14% respectively as compared to the control group. Both extracts significantly decreased the volume of intestinal fluid by 27%, 39.78%, and 50.1% for Q. coccinea respectively; and by 38.71%, 51.19%, and 60% for Q. robur respectively as compared to the control group. In addition, AME of Q. coccinea exhibited a peristaltic index of 53.48, 47.18, and 42.28 with significant inhibition of gastrointestinal transit by 18.98%, 28.53%, and 35.95 % respectively; while AME of Q. robur exhibited a peristaltic index of 47.71, 37, and 26.41 with significant inhibition of gastrointestinal transit by 27.72%, 43.89%, and 59.99% respectively as compared with the control group. Notably, Q. robur showed a better antidiarrheal effect in comparison with Q. coccinea and, the highest effect was observed for Q. robur at 1000 mg/kg as it was nonsignificant from the loperamide standard group in all measured parameters.

Compromised antigen binding and signaling interfere with bispecific CD19 and CD79a chimeric antigen receptor function.

Therapy with CD19-directed chimeric antigen receptor (CAR) T cells has transformed the treatment of advanced B-cell malignancies. However, loss of or low antigen expression can enable tumor escape and limit the duration of responses achieved with CAR T-cell therapy. Engineering bispecific CAR T cells that target 2 tumor antigens could overcome antigen-negative escape. We found that CD79a and b, which are heterodimeric components of the B-cell receptor, were expressed on 84.3% of lymphoma cases using immunohistochemistry, and 87.3% of CD79ab-positive tumors also coexpressed CD19. We generated 3 bispecific permutations: tandem, bicistronic, and pooled products of CD79a-CD19 or CD79b-CD19 CAR T cells and showed that bispecific CAR T cells prevented the outgrowth of antigen-negative cells in a CD19-loss lymphoma xenograft model. However, tandem and bicistronic CAR T cells were less effective than monospecific CD19 or CD79a CAR T cells for the treatment of tumors that only expressed CD19 or CD79, respectively. When compared with monospecific CAR T cells, T cells expressing a tandem CAR exhibited reduced binding of each target antigen, and T cells expressing a bicistronic CAR vector exhibited reduced phosphorylation of downstream CAR signaling molecules. Our study showed that despite added specificity, tandem and bicistronic CAR T cells exhibit different defects that impair recognition of tumor cells expressing a single antigen. Our data provide support for targeting multiple B-cell antigens to improve efficacy and identify areas for improvement in bispecific receptor designs.

MS/MS Molecular Networking Unveils the Chemical Diversity of Biscembranoid Derivatives, Neutrophilic Inflammatory Mediators from the Cultured Soft Coral Sarcophyton trocheliophorum.

Biscembranoids are the distinctive tetraterpenoids owing a 14/6/14 membered tricyclic scaffold that have been mainly discovered in the soft corals, especially the genera Sarcophyton, Lobophytum and Sinularia. Recent findings have demonstrated the great anti-inflammatory potential of biscembranoid analogues in human neutrophils, motivating more chemical and biological explorations targeting these marine-derived natural products. In the current study, the chemical diversity of biscembranoids derived from the cultured-type Sarcophyton trocheliophorum von Marenzeller was illustrated through MS/MS molecular networking (MN) profiling approach. Based on the MN patterns, the prioritization of unknown biscembranoid derivatives was putatively analyzed. As a result, the biscembrane targeting isolation afforded two new metabolites, sarcotrochelides A (1) and B (2), along with six known analogues (3-8). Their structures and relative configurations were determined by spectroscopic methods. In vitro neutrophil inflammatory inhibition was further investigated for all isolates based on reduced superoxide anion (O2•-) generation detections. Compounds 5-8 showed significant dose-dependently inhibitory effects, suggesting the cruciality of 6,7-dihydrooxepin-2(5H)-one moiety and saturated γ-lactone ring in their reactive oxygen species (ROS)-dependent anti-inflammatory properties.

Towards Sustainable Medicinal Resources through Marine Soft Coral Aquaculture: Insights into the Chemical Diversity and the Biological Potential.

In recent decades, aquaculture techniques for soft corals have made remarkable progress in terms of conditions and productivity. Researchers have been able to obtain larger quantities of soft corals, thus larger quantities of biologically active metabolites, allowing them to study their biological activity in many pharmacological assays and even produce sufficient quantities for clinical trials. In this review, we summarize 201 secondary metabolites that have been identified from cultured soft corals in the era from 2002 to September 2022. Various types of diterpenes (eunicellins, cembranes, spatanes, norcembranes, briaranes, and aquarianes), as well as biscembranes, sterols, and quinones were discovered and subjected to bioactivity investigations in 53 different studies. We also introduce a more in-depth discussion of the potential biological effects (anti-cancer, anti-inflammatory, and anti-microbial) and the mechanisms of action of the identified secondary metabolites. We hope this review will shed light on the untapped potential applications of aquaculture to produce valuable secondary metabolites to tackle current and emerging health conditions.

Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte.

Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.