Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Objective: To explore the possibility of performing allogeneic platelet-rich plasma (PRP) treatment for patients who were not suitable for autologous PRP collection through case reports of two patients with refractory wounds treated with allogeneic PRP. Methods: The ABO-compatible allogeneic whole blood was centrifuged 3 times to obtain allogeneic PRP within 6 hours of blood collection. Then the qualified allogeneic PRP was applied to 2 cases of refractory wound on the same day. Results: The platelet concentration in allogeneic PRP was higher than 1 000×10 /L, and the test results of infectious diseases, as well as the mixing of red blood cells and white blood cells, met the standard of quality control. Both patients achieved satisfactory wound healing outcomes (3 d). Conclusions: For patients who were not suitable for autologous PRP treatment, allogeneic PRP might be a new option.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

The 95% ethanol extract from bulbs of Narcissus tazetta var. chinensis(BNTC) was eluted with 30%, 60%, and pure methanol on D-101 macroporous resin. The elution fractions were isolated and purified by silica gel column chromatography, thin layer chromatography, D-101 macroporous resin, semi-preparative high performance liquid chromatography(HPLC), and HPLC. The purified compounds were identified using one-dimensional and two-dimensional spectroscopy, high-resolution mass spectrometry, and other techniques. A total of 15 compounds were isolated and identified as 5-(4-hydroxy-3-methoxyphenyl)-3-(4-hydroxyphenyl)-N-methyl-3,6-dihydropyridine-2(1H)-one(1), 3,5-di(hydroxyphenyl)-N-methyl-3,6-dihydropyridine-2(1H)-one(2), protocatechualdehyde(3), protocatechuic acid(4), 3,4-dihydroxyacetophenone(5), syringic acid(6), vanillic acid(7), p-hydroxybenzoic acid(8),(2S)-4'-hydroxy-7-methoxyflavan(9), 2,4,6-trimethoxyacetophenone(10), N-trans-ferulic acid p-hydroxyphenylethylamine(11), N-cis-p-coumaroyltyramine(12), N-trans-p-coumaroyltyramine(13), piscidic acid(14), 5-hydroxymethylfurfural(15). Compounds 1 and 2 are new compounds with similar structure that have not been reported yet, named narcissus A and narcissus B. Compounds 8-13 were isolated and identified from the genus Narcissus for the first time, and compounds 14 and 15 were isolated from BNTC for the first time. Compounds 1 and 2 inhibited the release of NO from RAW264.7 cells induced by lipopolysaccharide(LPS)(P<0.001), with compound 1 having an IC_(50) value of(72.76±2.97) μmol·L~(-1) and compound 2 having an IC_(50) value of(63.59±0.96) μmol·L~(-1).
Mice ; Animals ; Narcissus/chemistry* ; Drugs, Chinese Herbal/isolation & purification* ; Plant Roots/chemistry* ; Chromatography, High Pressure Liquid ; Macrophages/immunology* ; RAW 264.7 Cells

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

INTRODUCTION: Impostor phenomenon (IP) is a set of feelings encountered by individuals of being incompetent, despite experiencing successes. IP affects not only individuals on a personal level, but also organisations where the leadership diversity decreases due to employees' self-doubt. We aim to investigate the prevalence of IP and burnout among employees in the National University Health System (NUHS). METHODS: All permanently employed full-time NUHS employees aged 21 years and above were invited to participate in this self-administered cross-sectional study between April 2021 and August 2021. Mass emails with the embedded study link were sent every 2-3 weeks to the employees' corporate email accounts. RESULTS: In our study, 61% of our study respondents reported having IP experiences and 97% reported having burnout. The associations of IP with ethnicity and age group were significant. Post hoc tests, however, showed that the association was statistically significant only in the 21-29 years age group. CONCLUSION We found that there was no statistical significance between gender and the Maslach Burnout Inventory (MBI) profile types. However, we found that IP was significantly associated with individuals in the 21-29 years age group. This could be because younger individuals who just entered workforce may feel uncomfortable with their newfound independence and responsibility. Workplace support, such as workshops, and emotional support were found to be useful in helping individuals cope with IP. Future studies could be done post coronavirus disease 2019 (COVID-19) pandemic among healthcare workers to have a larger sample size to determine true IP and burnout prevalence.
Humans ; Singapore/epidemiology* ; Adult ; Male ; Female ; Burnout, Professional/psychology* ; Cross-Sectional Studies ; Prevalence ; Middle Aged ; Young Adult ; Surveys and Questionnaires ; COVID-19/epidemiology* ; Workplace/psychology*

INTRODUCTION: Workplace safety and health are interrelated - a worker who is not healthy may cause safety lapses at the workplace; conversely, safety lapses could affect the health of the workers. This study was part of a larger Total Workplace Safety and Health (WSH) programme run by the Workplace Safety and Health Council, Singapore. The objectives were to obtain a baseline health profile of workers across four major industries and identify important health risks for targeted workplace interventions. METHODS: Five service providers (SPs) were appointed to run the Total WSH programme. As part of the programme, SPs conducted an anonymous basic health survey among workers of participating companies. RESULTS: The responses of 6,373 respondents from the cleaning, construction, manufacturing, and transport and storage industries were studied. The overall response rate was 62%. Key health issues identified were high rates of obesity (22%) and smoking (24%) and low prevalence of regular exercise and healthy dietary habits. Chronic disease rates were similar to population self-reported rates (hypertension 15%, high lipid 12% and diabetes mellitus 6%). The workers reported high work stress (13%). CONCLUSION Health issues are prevalent in the workforce and may affect work and employee safety. It is increasingly important for employees' health to be considered in risk assessments and prioritised in workplace safety and health management systems and strategies. Health promotion interventions should be targeted, and multilevel and multicomponent initiatives should be integrated with pre-existing occupational safety programmes.
Humans ; Singapore/epidemiology* ; Occupational Health ; Male ; Female ; Adult ; Middle Aged ; Industry ; Workplace ; Health Surveys ; Surveys and Questionnaires ; Smoking/epidemiology* ; Obesity/epidemiology* ; Health Status ; Occupational Stress/epidemiology* ; Young Adult

INTRODUCTION: The study objective was to determine the levels of self-care and health literacy (HL) and their associations among patients with chronic kidney disease (CKD). METHODS: This was a cross-sectional, questionnaire-based study conducted in a public primary care setting in Singapore. A total of 289 participants aged 21-80 years with hypertension were recruited. Self-care profiles were measured using the Hypertension Self-Care Profile (HTN-SCP; range 0-240, domain range 0-80). Health literacy was measured using the Short-Form Health Literacy Scale (HLS-SF12; range 0-50, limited literacy ≤33). RESULTS: The mean self-care score was 182.7 (standard deviation [SD] 23.2). The median HL score was 34.7 (interquartile range [IQR] 31.9-40.3), and 31.1% of participants had limited HL. Self-care was not associated with age, CKD status, household income and education, but was associated with gender and HL score. In the final regression model, lower HL scores (adjusted β = 1.03, 95% confidence interval [CI] 0.7 to 1.36, P < 0.001) and male gender (adjusted β = -5.29, 95% CI -10.56 to -0.03, P = 0.049) were associated with lower self-care scores. The HL scores were associated with self-care domains of self-efficacy (HL: β = 0.30, 95% CI 0.17 to 0.42, P < 0.001), motivation (HL: β = 0.40, 95% CI 0.26 to 0.53, P < 0.001) and behaviour (HL: β = 0.38, 95% CI 0.26 to 0.50, P < 0.001). CONCLUSION Thirty-one percent of the participants had limited HL. Self-care was not associated with age, race, CKD status, household income or education. Male gender and limited HL were associated with lower self-care. Self-care was associated with self-efficacy, motivation and behaviour. Future research could focus on more targeted approaches to improve self-care and HL among patients with CKD.
Humans ; Male ; Female ; Health Literacy ; Middle Aged ; Self Care ; Cross-Sectional Studies ; Aged ; Adult ; Primary Health Care ; Renal Insufficiency, Chronic/therapy* ; Singapore ; Surveys and Questionnaires ; Aged, 80 and over ; Young Adult ; Hypertension/therapy*