Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy due to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from AD patients. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and reactive oxygen species (ROS) production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Barriers and Stimulus in Shared Decision Making Among Aesthetic Dermatologists in China: Findings from a Cross-Sectional Study.

Introduction: Shared decision making (SDM) is a collaborative process involving both healthcare providers and patients in making medical decisions, which gains increasing prominence in healthcare practice. But evidence on the level of SDM in medical practice and barriers as well as stimulus during the SDM implementation among aesthetic dermatologists is limited in China. Methods: From July to August 2023, 1938 dermatologists were recruited online in China. Data were collected through an electronic questionnaire covering: (1) demographic features; (2) SDM questionnaire physician version (SDM-Q-Doc); and (3) stimulus and barriers in SDM implementation. Logistic regression was applied to explore factors associated with SDM practice, barriers, and stimulus of SDM implementation, respectively. Results: The 1938 dermatologists included 1329 females (68.6%), with an average age of 35 years. The total SDM score ranged from 0 to 45, with a median value of 40 (IQR: 35-44), and the median stimulus score and barriers scores were 28 (IQR: 24-32) and 19 (IQR: 13-26), respectively. The prevalence of good SDM was 27.2%, logistic regression indicated that female dermatologists (odds ratio, OR=1.21, 95% confidence interval, CI: 0.96-1.51), and dermatologists with more years of aesthetic practice had a higher proportion of good SDM practice (OR was 1.44 for 5-9 years, 1.58 for 10-15 years and 1.77 for over 15 years). Moreover, female dermatologists and dermatologists with higher education level and serviced in private settings had lower barrier scores; female dermatologists and dermatologists with more years of aesthetic practice had higher stimulus scores. Conclusion: Chinese aesthetic dermatologists appear to implement SDM at an active level, with more stimulus and less barriers in SDM implementation. The integration of SDM into clinical practice among dermatologists is beneficial both for patients and dermatologists. Moreover, SDM practice should be strongly promoted and enhanced during medical aesthetics, especially among male dermatologists, dermatologists with less working experience, and those who work at public institutions.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

Real-world data of 5-aminolevulinic acid-mediated photodynamic therapy for Bowen's disease: A 10-year retrospective study in the skin of color patients (2011-2021).

BACKGROUND: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen's disease (BD). However, reported data on 5-aminolevulinic acid-mediated PDT (ALA-PDT) with red light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. METHODS: Medical records of BD patients who received ALA-PDT with red light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were performed to identify risk predictors. RESULTS: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first two years following ALA-PDT. CONCLUSION: ALA-PDT is an effective treatment for BD in the skin of color patients. Well-executed operation and effective pre-treatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, two years of follow-up is necessary following ALA-PDT.

Tobacco smoking negatively influences the achievement of greater than three-quarters reduction in psoriasis area and severity index after eight weeks of treatment among patients with psoriasis: Findings from a prospective study.

INTRODUCTION: Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. METHODS: Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI75) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. RESULTS: A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9-16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91-18.89), 14.14 (95% CI: 8.27-24.20), and 3.05 (95% CI: 1.20-7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI75 achievement. CONCLUSIONS: Tobacco smoking was negatively associated with PASI75 achievement both in current and former smokers, and former smokers had higher PASI75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.

Formononetin attenuates psoriasiform inflammation by regulating interferon signaling pathway.

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.

Event Graph Guided Compositional Spatial-Temporal Reasoning for Video Question Answering.

Video question answering (VideoQA) is challenging since it requires the model to extract and combine multi-level visual concepts from local objects to global actions from complex events for compositional reasoning. Existing works represent the video with fixed-duration clip features that make the model struggle in capturing the crucial concepts in multiple granularities. To overcome this shortcoming, we propose to represent the video with an Event Graph in a hierarchical structure whose nodes correspond to visual concepts of different levels (object, relation, scene and action) and edges indicate their spatial-temporal relationships. We further propose a H ierarchical S patial- T emporal T ransformer (HSTT) which takes nodes from the graph as visual input to realize compositional reasoning guided by the event graph. To fully exploit the spatial-temporal context delivered from the graph structure, on the one hand, we encode the nodes in the order of their semantic hierarchy (depth) and occurrence time (breadth) with our improved graph search algorithm; On the other hand, we introduce edge-guided attention to combine the spatial-temporal context among nodes according to their edge connections. HSTT then performs QA by cross-modal interactions guaranteed by the hierarchical correspondence between the multi-level event graph and the cross-level question. Experiments on the recent challenging AGQA and STAR datasets show that the proposed method clearly outperforms the existing VideoQA models by a large margin, including those pre-trained with large-scale external data. Our code is available at https://github.com/ByZ0e/HSTT.

The risk factors of diabetic ketosis and diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a retrospective study.

BACKGROUND: There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China. RESEARCH DESIGN AND METHODS: Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA. RESULTS: A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45-6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06-3.38)], Metformin [OR = 1.84, 95% CI (1.01-3.38)], and Insulin [OR = 1.93, 95% CI (1.02-3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA. CONCLUSIONS: Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.

The therapeutic efficacy and mechanism action of Si Cao formula in the treatment of psoriasis: A pilot clinical investigation and animal validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammation and relapsing disease that affected approximately 100 million individuals worldwide. In previous clinical study, it was observed that the topical application of Si Cao Formula (SCF) ameliorated psoriasis skin lesions and reduced the recurrence rate of patients over a period of three months. However, the precise mechanism remains unclear. AIM OF THE STUDY: The objective of this study was to assess the effectiveness and safety of SCF in patients diagnosed with psoriasis and explore the molecular mechanisms that contribute to SCF's therapeutic efficacy in psoriasis treatment. MATERIALS AND METHODS: A randomized, controlled, and pilot clinical study was performed. This study assessed 30 individuals diagnosed with mild to moderate plaque psoriasis. 15 of them underwent local SCF treatment, the others received calcipotriol intervention. The outcome measure focused on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and recurrence rate. In addition, IMQ-induced psoriasis-like mice model were used to assess the impact of SCF on ameliorating epidermal hyperplasia, suppressing angiogenesis, and modulating immune response. Furthermore, we performed bioinformatics analysis on transcriptome data obtained from skin lesions of mice model. This analysis allowed us to identify the targets and signaling pathways associated with the action of SCF. Subsequently, we conducted experimental validation to confirm the core targets. RESULTS: Our clinical pilot study demonstrated that SCF could ameliorate skin lesions in psoriasis patients with comparable efficacy of calcipotriol in drop of PASI and DLQI scores. SCF exhibited a significantly reduced recurrence rate within 12 weeks (33.3%). Liquid Chromatography Mass Spectrometry (LC-MS) identified 41 active constituents of SCF (26 cations and 15 anions). Animal experiments showed SCF ameliorates the skin lesions of IMQ-induced psoriasis like mice model and suppresses epidermal hyperkeratosis and angiogenesis. There were 845 up-regulated and 764 down-regulated DEGs between IMQ and IMQ + SCF groups. GO analysis revealed that DEGs were linked to keratinization, keratinocyte differentiation, organic acid transport epidermal cell differentiation, and carboxylic acid transport interferon-gamma production. KEGG pathway analysis showed that SCF may play a vital part through IL-17 and JAK/STAT signaling pathway. In addition, SCF could reduce the number of positive cells expressing PCNA, CD31, pSTAT3, CD3, and F4/80 within the epidermis of psoriatic lesions, as well as the expression of Il-17a and Stat3 in IMQ-induced psoriasis mice. CONCLUSIONS: Our research suggests that SCF serves as a reliable and efficient local approach for preventing and treating psoriasis. The discovery of plausible molecular mechanisms and therapeutic targets associated with SCF may support its broad implementation in clinical settings.

Natural hair color and skin cancers: A two-sample Mendelian randomization study.

Previous observational studies have indicated an association between hair color and the risk of melanoma and keratinocyte skin cancer (KSC); however, different hair colors show inconsistent effects on skin cancers. Here, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between natural hair color and skin cancers by using 211 single nucleotide polymorphisms as genetic instruments from a genome-wide meta-analysis of 360,270 individuals of European ancestry. Light hair colors (red, blonde, and light brown) were associated with high levels of cutaneous melanoma (CM) and KSC (CM-inverse variance weighted [IVW] odds ratio [OR]-red: 1.034, 95% confidence interval [CI]: 1.025-1.044, P < 0.001; OR-blonde: 1.008, 95% CI: 1.003-1.014, P = 0.003; OR-light brown: 1.006, 95% CI: 1.002-1.011, P = 0.009; KSC-IVW OR-red: 1.078, 95% CI: 1.053-1.103, P < 0.001; OR-blonde: 1.024, 95% CI: 1.009-1.040, P = 0.002; OR-light brown: 1.018, 95% CI: 1.004-1.033, P = 0.01). However, dark brown hair showed an inverse causal relationship with skin cancers (CM IVW OR: 0.987, 95% CI: 0.984-0.990, P < 0.001; KSC IVW OR: 0.979, 95% CI: 0.970-0.988, P < 0.001). Black hair was associated with a decreased risk of KSC (IVW OR: 0.954, 95% CI: 0.913-0.997, P = 0.036) but showed no causal relationship with CM. The present study provides strong MR evidence of a causal association between hair color and skin cancer. Secondary MR analyses enhances result robustness by replicating findings, exploring gender-specific effects, and providing a more comprehensive understanding of the complex relationship between hair color and skin cancers. More large-scale MR studies or randomized controlled trials are required to further investigate the mechanisms of the association between hair color and skin cancers.

Hemostasis after transradial coronary intervention by rotary compression device with sterile gauze is associated with more adverse events: a retrospective study.

OBJECTIVE: We investigated the relationship between using a rotary compression device (RCD) with or without sterile gauze and adverse events in transradial access (TRA) for coronary intervention. METHODS: In this study involving 933 patients at Yueyang Hospital, we recorded TRA-related adverse events, such as bleeding, forearm hematoma, swollen palms, radial artery occlusion (RAO) and others. Logistic regression was applied to assess the association. RESULTS: Of the 933 patients (66.7% males, average age 67.8 years), 511 used RCD with sterile gauze, whereas 422 used RCD without sterile gauze. The most common adverse events were radial artery hemorrhage (7.4%), hand swelling (4.8%) and RAO (4.6%). Logistic regression analysis revealed that the use of RCD with sterile gauze was associated with a higher prevalence of adverse events [odds ratio (OR), 1.74; 95% confidence interval (CI), 1.22-2.49), even with the adjustment of potential confounders (OR, 1.71; 95% CI, 1.19-2.45). Moreover, patients who used RCD with sterile gauze exhibited an increased risk of radial artery hemorrhage (OR, 1.83; 95% CI, 1.07-3.12), swelling of the hand (OR, 1.96; 95% CI, 1.02-3.75) and RAO (OR, 3.17; 95% CI, 1.49-6.72). CONCLUSIONS: The use of RCD with sterile gauze in TRA is associated with a higher incidence of adverse events.

Jianpi Huayu Decoction suppresses cellular senescence in colorectal cancer via p53-p21-Rb pathway: Network pharmacology and in vivo validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huayu Decoction (JHD) is an herbal prescription in traditional Chinese medicine based on Sijunzi Decoction to treat patients with colorectal cancer (CRC). Its effects on the inhibition of CRC cell proliferation and tumor growth are promising; however, its multicomponent nature makes a complete understanding of its mechanism challenging. AIM OF THE STUDY: To explore the therapeutic targets and underlying molecular pathways of JHD in CRC treatment using network pharmacology techniques and in vivo validation. MATERIALS AND METHODS: The active ingredients and targets of JHD were identified, compound-target interactions were mapped, and enrichment analyses were conducted. We identified the hub targets of JHD-induced cellular senescence in CRC. The binding affinities between compounds and targets were evaluated through molecular docking. Subsequently, we conducted bioinformatic analyses to compare the expression of hub targets between colorectal tissue and normal tissue. Finally, in vivo experiments were carried out utilizing a xenograft model to assess the effects of JHD on cellular senescence biomarkers. RESULTS: Network pharmacology revealed 129 active ingredients in JHD that were associated with 678 targets, leading to the construction of compound-target and target-pathway networks. Enrichment analyses highlighted key pathways including cellular senescence. Based on this, hub targets associated with cellular senescence were determined and validated. Molecular docking indicated favorable interactions between the active components and hub targets. Gene expression and survival analysis in CRC tissue were consistent with the potential roles of hub genes. Animal experiments showed that JHD triggered cellular senescence and suppressed the growth of CRC by regulating the p53-p21-Rb signaling pathway. CONCLUSIONS: This research adopted network pharmacology, bioinformatics, and animal experiments to unveil that JHD induces cellular senescence in CRC by influencing the p53-p21-Rb pathway and senescence-associated secretory phenotypes, highlighting its potential as a CRC treatment.

More Physical Exercise is Required for Overweight or Obese Women with Gestational Diabetes Mellitus to Achieve Good Plasma Glucose Control During Pregnancy: Finding from a Prospective Cohort in Shanghai.

Objective: This study was based on a gestational diabetes mellitus (GDM) cohort in Shanghai to examine the association between physical exercise and plasma glucose control among GDM women with and determine what the effects of pre-pregnancy body mass index (BMI). Methods: In this study, GDM was diagnosed if the plasma glucose values at any of the following time points reached the diagnostic threshold: fasting blood glucose (5.1 mmol/L), 1-hour blood glucose (10.0 mmol/L), and 2-hour blood glucose (8.5 mmol/L) by 75 g oral glucose tolerance test (OGTT). Information on GDM women was extracted from the hospital's health records and prenatal examination forms and was obtained through face-to-face interviews after delivery. A restricted cubic spline curve with four knots was used to flexibly model the relationship between the duration of moderate-intensity physical exercise and the percentage of abnormal plasma glucose among GDM patients with different BMI values. In this study, a P-value less than 0.05 (two-tailed) was considered as statistical significance. Results: Among 1139 GDM women with GDM, the median percentage of abnormal plasma glucose (PG) was 40.0% (interquartile range (IQR): 20.0-66.7%), and the difference between overweight-obese group and underweight-normal group was statistically significant (50.0% vs 40.0%, P <0.001). In this study, engaging in more physical exercise during pregnancy contributed to a higher prevalence of satisfactory glycemic control, and women with BMI <25 kg/m2 should engage in no less than 90 minutes of moderate-intensity physical activity per day to achieve satisfactory glycemic control (prevalence of abnormal PG <35%). However, over 120 minutes of daily moderate-intensity physical activity is required for GDM women with a BMI ≥25 kg/m2 to achieve satisfactory glycemic control. Conclusion: Overweight or obese women with GDM have a higher risk of poor glycemic control and require a longer duration of physical exercise to achieve the same level of blood glucose control.

Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence.

BACKGROUND: Jueyin granules (JYG) is effective against psoriasis, but its utility components are not clear. Rutin is the main monomer of JYG, its therapeutic effect and mechanism on psoriasis need to be further clarified. PURPOSE: To explore the potential mechanisms of rutin on psoriasis through network pharmacology and experiments. METHODS: In vitro, cell viability was determined using the CCK8 assay, and inflammatory factors were identified using RT-qPCR. The hub genes and kernel pathways of action were identified by modular pharmacology analysis. In vivo, a BALB/c mice model of psoriasis was induced by Imiquimod (IMQ). The therapeutic effect and action pathway were detected through Western Blotting, RT-qPCR, histopathologic and immunohistochemical analysis. RESULTS: Rutin inhibited cell proliferation and expression of TNF-α and IL-6 in HaCaT cells. The hub genes include APP, INS, and TNF, while the kernel pathways contain the AGE-RAGE signaling pathway. In IMQ-induced psoriasis-like mice, rutin ameliorated skin lesions and inhibited cell proliferation. Rutin could attenuate inflammation by downregulating the AGE-RAGE signaling pathway. CONCLUSION: This study suggests that rutin can reduce IMQ-induced psoriasis like skin inflammation in mice, and regulation of AGE-RAGE signaling pathway may be one of its potential anti-inflammatory mechanisms. Rutin has a promising therapeutic use for the treatment of psoriasis.

Oral administration of hyaluronic acid to improve skin conditions via a randomized double-blind clinical test.

OBJECTIVE: To evaluate the impact of oral intake of Hyaluronic Acid (HA) on skin health. BACKGROUND: HA, an endogenous substance in the human body, plays a key role in skin health. However, its concentration in the skin decreases significantly with age. Previous studies suggested that oral intake of HA can supplement the body's HA level, but did not reveal the effects on different age groups and skin types. METHODS: A double-blind, randomized clinical trial with 129 female participants, covering young and elderly groups and differnet skin types, was conducted to assess the efficacy of orally administered HA on skin health. RESULTS: Oral administration of HA significantly promoted skin hydration after 2-8 weeks among both young and elderly groups. Skin tone improvement was observed after 4-8 weeks, while an increase in epidermal thickness was noted after 12 weeks. CONCLUSION: This study provides direct evidence supporting the clinical efficacy of oral intake of HA in promoting skin health.

Visual mapping of global nanoplastics research progresses and hotspots: a scientometric assessment analysis.

Environmental plastic wastes are continuously degraded into microplastics (MPs) and nanoplastics (NPs); the latter are more potentially harmful to organisms and human health as their smaller size and higher surface-to-volume ratio. Previous reviews on NPs mainly concentrate on specific aspects, such as sources, environmental behavior, and toxicological effects, but few focused on NPs-related scientific publications from a global point of view. Therefore, this bibliometric study aims to summarize the research themes and trends on NPs and also propose potential directions for future inquiry. Related papers were downloaded from the Web of Science Core Collection database on NPs published from 2008 to 2021, and then retrieved information was analyzed using CiteSpace 6.1 R2 and VOSviewer (version 1.6.). Research on NPs mainly involved environmental behaviors, toxicological effects, identification and extraction of NPs, whereas aquatic environments, especially marine systems, attracted more attentions from these scientists compare to terrestrial environments. Furthermore, the adsorption behavior of pollutants by NPs and the toxicological effects of organisms exposed to NPs are the present hotspots, while the regulation of humic acid (HA) on NPs behaviors and the environmental behavior of NPs in freshwater, like rivers and lakes, are the frontier areas of research. This study also explored the possible opportunities and challenges that may be faced in NPs research, which provide a valuable summary and outlook for ongoing NPs-related research, which may be of intrigue and noteworthiness for relevant researchers.

Spatiotemporal patterns and main driving factors of drainage water quality of an arid irrigation district with shallow groundwater table.

Drainage water quality is a crucial factor reflecting the regime of agricultural non-point source pollution in irrigation districts and is closely related to land use, soil texture, cropping pattern, fertilization, and irrigation and drainage conditions. However, the response of drainage water quality to various natural and anthropogenic factors needs further exploration in irrigation districts affected by shallow groundwater table. Spatiotemporal patterns of chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), and ammonium nitrogen (NH4-N) were monitored and analyzed in ten agricultural drainage ditches in the arid region of China from 2011 to 2019. Spatially, water pollution in agricultural drainage ditches with small water quantity can be significantly exacerbated by urban sewage, whereas a large amount of agricultural drainage can effectively dilute the pollution of urban sewage. Severe soil salinization in the cropland increases the risk of water pollution due to easier losses of soil nutrient and organic matter. Soil salinization is a key factor in the crop distribution pattern based on the crop salt tolerance, and the maize/wheat field with a higher fertilizer application rate generally results in poorer drainage water quality. Temporally, for the agricultural drainage ditches, the monthly and annual COD, TP, TN, and NH4-N concentrations fluctuate inversely with drainage water quantity and are positively correlated with fertilizer application, among which the monthly COD concentration in drainage water has larger variation in severe salinized areas. There exist critical annual and monthly drainage amounts, above which the probabilities of higher concentrations of COD, TP, TN, and NH4-N reduce greatly.

Genetic evidence behind the Cd resistance of wild Metaphire californica: The global RNA regulation rather than specific mutation of well-known gene.

Heavy metal contamination presents a profound threat to terrestrial biodiversity, yet the genetic adaptation and evolution of field organisms under persistent stress are poorly understood. In this study, the Cd-resistant earthworms Metaphire californica collected from the control (Meihua, MHC) and elevated-pollution (Lupu, LPC) pairwise sites were used to elucidate the underlying genetic mechanism. A 48-h acute test showed that LPC worms exhibited 2.34 times higher LC50 (50% lethal concentration values) compared to MHC ones. The Cd bioaccumulation, metallothionein (MT) protein contents, and MT gene expression of LPC M.californica were all significantly higher than those of MHC worms. The well-known MT gene of M.californica was successfully cloned and identified, however, the encoding nucleotide and amino acids displayed non-observable mutations and the phylogenetic tree also revealed that different populations clustered together. Additionally, the results of transcriptomics sequencing demonstrated 173 differentially expressed genes between LPC and MHC worms, primarily involved in stress-response and detoxification pathways, including signal transduction, material metabolism, and protein exports. The above results confirmed that the crucial MT gene did not undergo genetic mutations but rather exhibited global mRNA regulation responsible for the Cd resistance of M.californica. The current study partially disclosed the stress adaptation and evolution of organisms under long-term in situ contamination, which provides insights into maintaining biodiversity under adverse environment.