Mechanisms of action of Shizhenqing granules for eczema treatment: Network pharmacology analysis and experimental validation.

Background: Jiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation. Methods: The main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the "herbal compound-potential target" and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema. Results: Using UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats. Conclusion: This study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

Effects of the periodic fasting-mimicking diet on health, lifespan, and multiple diseases: a narrative review and clinical implications.

Dietary restriction and fasting have been recognized for their beneficial effects on health and lifespan and their potential application in managing chronic metabolic diseases. However, long-term adherence to strict dietary restrictions and prolonged fasting poses challenges for most individuals and may lead to unhealthy rebound eating habits, negatively affecting overall health. As a result, a periodic fasting-mimicking diet (PFMD), involving cycles of fasting for 2 or more days while ensuring basic nutritional needs are met within a restricted caloric intake, has gained widespread acceptance. Current research indicates that a PFMD can promote stem cell regeneration, suppress inflammation, extend the health span of rodents, and improve metabolic health, among other effects. In various disease populations such as patients with diabetes, cancer, multiple sclerosis, and Alzheimer's disease, a PFMD has shown efficacy in alleviating disease symptoms and improving relevant markers. After conducting an extensive analysis of available research on the PFMD, it is evident that its advantages and potential applications are comparable to other fasting methods. Consequently, it is proposed in this review that a PFMD has the potential to fully replace water-only or very-low-energy fasting regimens and holds promise for application across multiple diseases.

Association of marine PUFAs intakes with cardiovascular disease, all-cause mortality, and cardiovascular mortality in American adult male patients with dyslipidemia: the U.S. National Health and Nutrition Examination Survey, 2001 to 2016.

BACKGROUND: The relationship between marine polyunsaturated fatty acid (PUFA) intake and cardiovascular disease and mortality in dyslipidemic patients is unclear. Men with dyslipidemia have a higher risk of cardiovascular disease than women, and PUFA supplementation may be more beneficial in men. OBJECTIVE: The purpose of this study was to assess the relationship between different types of marine polyunsaturated fatty acids intakes and cardiovascular disease, all-cause mortality, and cardiovascular mortality in adult U.S. males with dyslipidemia. METHODS: The study ultimately included 11,848 adult men with dyslipidemia who were screened from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2016. This was linked to the 2019 National Death Index (NDI) records to establish a prospective cohort. In the study, a logistic regression model was established to assess the relationship between PUFA intake and prevalent CVD, and a Cox proportional hazards regression model was established to assess the relationship between PUFA intake and death. RESULTS: In the fully adjusted models, compared with participants in the lowest tertile, participants with the highest DPA intake were associated with a lower risk of CVD (CVD: OR = 0.71, 95%CI: 0.55, 0.91; angina: OR = 0.54, 95%CI: 0.38, 0.79; stroke: OR = 0.62, 95%CI: 0.43, 0.89), but not with three subtypes of congestive heart failure, coronary heart disease, and myocardial infarction. And the highest tertile level of DPA intake can reduce all-cause mortality (HR = 0.77, 95%CI: 0.64, 0.91) and CVD mortality (HR = 0.68, 95%CI: 0.52, 0.90). CONCLUSIONS: Cardiovascular disease risk, all-cause mortality, and CVD mortality were inversely associated with dietary DPA intake but not EPA and DHA intakes in U.S. male participants with dyslipidemia.

Seasonal differences in intestinal flora are related to rats' intestinal water metabolism.

Many studies have reported obvious seasonal differences in the intestinal flora of rats, and this stable distribution of the seasonal flora helps in maintaining the normal physiological function of the host. However, the mechanism underlying these seasonal differences in intestinal flora remains unclear. To explore the correlation among seasonal factors and intestinal water metabolism and intestinal flora, 20 Sprague Dawley (SD) rats were divided into spring, summer, autumn, and winter groups. The environment for the four seasons was simulated using the Balanced Temperature and Humidity Control system. The intestinal water metabolism was evaluated by determining the intestinal transmission function, fecal water content, water content of colonic tissue, and the colonic expression levels of AQP3, AQP4, and AQP8. The composition and relative abundance of intestinal microflora in rats in each season were assessed through 16S rDNA amplifier sequencing, and the relationship between the dominant flora and intestinal water metabolism in each season was analyzed using Spearman correlation analysis. The high temperature and humidity season could lead to an increase in intestinal water metabolism and intestinal water content in rats, whereas the low temperature and humidity season could lead to a decrease, which was closely related to the change in microflora. To explore the molecular mechanism of seasonal changes in intestinal water metabolism, the concentration of colonic 5-HT, VIP, cAMP, and PKA associated with intestinal water metabolism in rats were also examined. Seasonal changes could affect the concentration of colonic 5-HT and VIP in rats, and then regulate AQPs through cAMP/PKA pathway to affect the intestinal water metabolism. These results suggest that seasonal factors affect the level of intestinal water metabolism in rats and result in seasonal differences in intestinal flora.

Nonoperative Management of Blunt Splenic Trauma: Outcomes of Gelfoam Embolization of the Splenic Artery.

CONTEXT: Nonoperative management (NOM) is the standard of care in hemodynamically stable trauma patients with blunt splenic injury. Gelfoam splenic artery embolization (SAE) is a treatment option used in trauma patients. AIMS: The primary aim of this study was to retrospectively examine the use and outcomes of Gelfoam SAE in adult patients with blunt splenic injury. SETTINGS AND DESIGN: One hundred and thirty-two adult patients with blunt splenic injury admitted to a Level 1 trauma center between January 2014 and December 2015 were included in the study. Patients treated with Gelfoam SAE, NOM, and splenectomies were reviewed. Descriptive statistics including patient age, Glasgow Coma Scale, Injury Severity Score (ISS), hospital days, Intensive Care Unit (ICU) days, splenic grade, and amount of blood products administered were recorded. Complications, defined as any additional factors that contributed to the patient's overall length of hospital stay, were compared between the three groups. Technical aspects of Gelfoam SAE and associated complications were reviewed. SUBJECTS AND METHODS: Gelfoam SAE was performed in 25 (18.9%) of the 132 patients. Gelfoam SAE patients had fewer ICU days compared with those patients who had a splenectomy or NOM. There was no statistical difference in complications between patients who underwent Gelfoam SAE and those who did not. Patients who underwent Gelfoam SAE tended to have fewer complications including deep venous thrombosis's, PE, and infections and yielded no complications in 64% of the Gelfoam group. STATISTICAL ANALYSIS: Statistical analysis included descriptives, ANOVA, and nonparametric tests as appropriate. CONCLUSION: Gelfoam SAE can be used for blunt splenic injury for intermediate ISS and splenic grade as it reduced hospital and ICU days.

Association of Melatonin Production with Seasonal Changes, Low Temperature, and Immuno-Responses in Hamsters.

Seasonal changes impact the melatonin production and immuno-activities in vertebrates. This is believed due to the photoperiodic alterations of the different seasons which impact the functions of pineal gland. The short photoperiod promotes pineal melatonin production. As a result, during the winter, animals have significantly higher levels of melatonin than in summer. However, the seasonal changes also include temperature changes. This factor has never been systemically investigated in animals. In the current study, we observed that increased temperature had limited influence on melatonin production. In contrast, cold temperature is the major factor to induce melatonin production in hamsters. Cold temperature per se can upregulate the expressions of melatonin synthetic gene AANAT and ASMT, which are the important enzymes for melatonin biosynthesis. The elevated melatonin levels induced by the cold exposure in hamster in turn, improve the immuno-responses of the animals with increased levels of IL1, 6, and 10 as well CD3. In addition, melatonin as a potent antioxidant and thermogenic agent would improve the survival chance of animals during cold weather.

Inhibitory effect of Sumu (Lignum Sappan) plus Fuzi (Radix Aconiti Lateralis Praeparata) on a lung carcinoma model.

OBJECTIVE: To investigate the inhibitory effect of Sumu (Lignum Sappan) plus Fuzi (Radix Aconiti Lateralis Praeparata) (SF) on the growth and metastasis of Lewis lung carcinoma. METHODS: A lung carcinoma model was established by subcutaneously inoculating Lewis lung carcinoma cells into C57BL/6 mice. The mice were randomly divided into four groups of 13 mice (control, low-dose, moderate-dose, and high-dose), and gavaged once-daily for 21 consecutive days. The rates of tumor inhibition, metastasis, and metastasis inhibition were observed. The differential expressions of sP-selectin and vascular endothelial growth factor C (VEGFC) were compared between the treatment groups and the control group. RESULTS: The tumor weights differed significantly between the treatment groups and the control group (P < 0.05). Administration of SF in the moderate-dosage and low-dose groups significantly inhibited the expression of sP-selectin and VEGFC (both P < 0.05), suggesting anti-tumor activity. CONCLUSION: SF can inhibit the growth and metastasis of Lewis lung carcinoma.

A Chinese herbal medicine (Modified Guomin Decoction) Influences the differentiation of CD4+ T-cell subsets in OVA-induced asthmatic mice.

OBJECTIVE: Modified Guomin Decoction (MGD) is an effective Chinese herbal medicine for treatment of various allergic diseases, especially allergic asthma. Its water decoction is conventionally used for treatment of allergic bronchitis in China. Up to date, the underlying mechanisms of this herbal combination have not been fully investigated yet. METHODS: In the in vivo study, the mice were treated with Chicken egg ovalbumin (OVA) and aluminum hydroxide gel as the classic allergic asthma animal model. After treatment with MGD, the lung tissues were examined by Histological assessment. The flow cytometric analysis was used to classify the CD4+ T-cell subsets. RT-PCR, Real time fluorescence quota PCR and Western blotting were used to analyze the gene expression of IL-4, IL-5, IFN-γ T-bet/GAIA-3 and Foxp3 in lung tissues. RESULTS: MGD significantly reduced ovalbumin-specific IgE production in mouse serum and suppressed inflammatory cell infiltration, thus, improved the asthma symptoms. The mechanistic studies indicated that MGD treatment mainly modified the differentiation of CD4+ T-cell subsets and improved their functions. These included that MGD enhanced the proportion of Th1-cell, reduced Th2-cell subsets to CD4+ cell and balanced Treg/Th17 cell populations in the asthmatic mice spleen tissues. For Th1-cells, MGD upregulated the gene expression of their cytokine IFN-γ and its transcription factor T-bet while it downregulated the gene expression of their cytokines of IL-4 and IL-5. For Th2-cells, MGD mainly downregulated its transcription factor GATA-3 in lung tissues of asthmatic mice. MGD suppressed the Th17-cell subsets in CD4+ cells and upregulated the expression of Foxp3, a specific transcription factor of Treg-cell.

Alterations of reproductive hormones and receptors of male rats at the winter and summer solstices and the effects of pinealectomy.

BACKGROUND: Photoperiodic changes mediate certain physiological or pathological alterations in organisms. Solstices represent either the longest or shortest photoperiod of a year. OBJECTIVES: Intact and pinealectomized rats were used to investigate the potential changes of reproductive hormones in the hypothalamus-pituitary-testis (HPT) axis including GnRH, FSH, LH, testosterone and melatonin, and their receptors at summer solstice (SS) and winter solstices (WS). METHODS: The levels of reproductive hormones in HPT axis and the binding characteristics of their receptors were examined using radioimmunoassay and radioreceptor assay techniques, respectively. RESULTS: The results indicate that in the intact male rat, GnRH, LH and testosterone are higher at the SS than at the WS. However, FSH exhibited no significant seasonal changes. In the testis, Bmax and Kd of LH receptors are higher at the WS than at the SS while those of FSH receptors are higher at the SS than at the WS. In addition, the melatonin in HPT axis appeared significant differences between WS and SS. Bmax and Kd of melatonin receptors in the hypothalamus and pituitary also showed higher at the WS than at the SS. Moreover, reproductive hormone production lost their seasonal rhythms after pinealectomy. CONCLUSION: The most important discovery in this study is that we first reported that pinealectomy had profound effects on the binding characteristics of melatonin with its subtype receptors. Especially at the hypothalamus, the dominated melatonin receptors shifted from MT1 to MT2 after pinealectomy at the two solstices.

Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression.

Obesity has become an epidemic in industrialized and developing countries. In 30 years, unless serious changes are made, a majority of adults and many children will be classified as overweight or obese. Whereas fatness alone endangers physiological performance of even simple tasks, the associated co-morbidity of obesity including metabolic syndrome in all its manifestations is a far more critical problem. If the current trend continues as predicted, health care systems may be incapable of handling the myriad of obesity-related diseases. The financial costs, including those due to medical procedures, absenteeism from work, and reduced economic productivity, will jeopardize the financial well-being of industries. The current review summarizes the potential contributions of three processes that may be contributing to humans becoming progressively more overweight: circadian or chronodisruption, sleep deficiency, and melatonin suppression. Based on the information provided in this survey, life-style factors (independent of the availability of abundant calorie-rich foods) may aggravate weight gain. Both epidemiological and experimental data support associations between disrupted physiological rhythms, a reduction in adequate sleep, and light-at-night-induced suppression of an essential endogenously produced molecule, melatonin. The implication is that if these problems were corrected with life-style changes, body-weight could possibly be more easily controlled.

Melatonin protection from chronic, low-level ionizing radiation.

In the current survey, we summarize the published literature which supports the use of melatonin, an endogenously produced molecule, as a protective agent against chronic, low-level ionizing radiation. Under in vitro conditions, melatonin uniformly was found to protect cellular DNA and plasmid super coiled DNA from ionizing radiation damage due to Cs(137) or X-radiation exposure. Likewise, in an in vivo/in vitro study in which humans were given melatonin orally and then their blood lymphocytes were collected and exposed to Cs(137) ionizing radiation, nuclear DNA from the cells of those individuals who consumed melatonin (and had elevated blood levels) was less damaged than that from control individuals. In in vivo studies as well, melatonin given to animals prevented DNA and lipid damage (including limiting membrane rigidity) and reduced the percentage of animals that died when they had been exposed to Cs(137) or Co(60) radiation. Melatonin's ability to protect macromolecules from the damage inflicted by ionizing radiation likely stems from its high efficacy as a direct free radical scavenger and possibly also due to its ability to stimulate antioxidative enzymes. Melatonin is readily absorbed when taken orally or via any other route. Melatonin's ease of self administration and its virtual absence of toxicity or side effects, even when consumed over very long periods of time, are essential when large populations are exposed to lingering radioactive contamination such as occurs as a result of an inadvertent nuclear accident, an intentional nuclear explosion or the detonation of a radiological dispersion device, i.e., a "dirty" bomb.

Glucose: a vital toxin and potential utility of melatonin in protecting against the diabetic state.

The molecular mechanisms including elevated oxidative and nitrosative reactants, activation of pro-inflammatory transcription factors and subsequent inflammation appear as a unified pathway leading to metabolic deterioration resulting from hyperglycemia, dyslipidemia, and insulin resistance. Consistent evidence reveals that chronically-elevated blood glucose initiates a harmful series of processes in which toxic reactive species play crucial roles. As a consequence, the resulting nitro-oxidative stress harms virtually all biomolecules including lipids, proteins and DNA leading to severely compromised metabolic activity. Melatonin is a multifunctional indoleamine which counteracts several pathophysiologic steps and displays significant beneficial effects against hyperglycemia-induced cellular toxicity. Melatonin has the capability of scavenging both oxygen and nitrogen-based reactants and blocking transcriptional factors which induce pro-inflammatory cytokines. These functions contribute to melatonin's antioxidative, anti-inflammatory and possibly epigenetic regulatory properties. Additionally, melatonin restores adipocyte glucose transporter-4 loss and eases the effects of insulin resistance associated with the type 2 diabetic state and may also assist in the regulation of body weight in these patients. Current knowledge suggests the clinical use of this non-toxic indoleamine in conjunction with other treatments for inhibition of the negative consequences of hyperglycemia for reducing insulin resistance and for regulating the diabetic state.

Alzheimer's disease: pathological mechanisms and the beneficial role of melatonin.

Alzheimer's disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition. Perhaps the best-known hypothesis to explain AD is that which involves the role of the accumulation of amyloid-ß peptide in the brain. Other theories that have been invoked to explain AD and summarized in this review include the cholinergic hypothesis, the role of neuroinflammation, the calcium hypothesis, the insulin resistance hypothesis, and the association of AD with peroxidation of brain lipids. In addition to summarizing each of the theories that have been used to explain the structural neural changes and the pathophysiology of AD, the potential role of melatonin in influencing each of the theoretical processes involved is discussed. Melatonin is an endogenously produced and multifunctioning molecule that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD. Production of this indoleamine diminishes with increasing age, coincident with the onset of AD. In addition to its potent antioxidant and anti-inflammatory activities, melatonin has a multitude of other functions that could assist in explaining each of the hypotheses summarized above. The intent of this review is to stimulate interest in melatonin as a potentially useful agent in attenuating and/or delaying AD.

Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science.

The presence of melatonin in plants is universal. Evidence has confirmed that a major portion of the melatonin is synthesized by plants themselves even though a homologue of the classic arylalkylamine N-acetyltransferase (AANAT) has not been identified as yet in plants. Thus, the serotonin N-acetylating enzyme in plants may differ greatly from the animal AANAT with regard to sequence and structure. This would imply multiple evolutionary origins of enzymes with these catalytic properties. A primary function of melatonin in plants is to serve as the first line of defence against internal and environmental oxidative stressors. The much higher melatonin levels in plants compared with those found in animals are thought to be a compensatory response by plants which lack means of mobility, unlike animals, as a means of coping with harsh environments. Importantly, remarkably high melatonin concentrations have been measured in popular beverages (coffee, tea, wine, and beer) and crops (corn, rice, wheat, barley, and oats). Billions of people worldwide consume these products daily. The beneficial effects of melatonin on human health derived from the consumption of these products must be considered. Evidence also indicates that melatonin has an ability to increase the production of crops. The mechanisms may involve the roles of melatonin in preservation of chlorophyll, promotion of photosynthesis, and stimulation of root development. Transgenic plants with enhanced melatonin content could probably lead to breakthroughs to increase crop production in agriculture and to improve the general health of humans.