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BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.
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BACKGROUND: In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking. OBJECTIVE: To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo. PATIENTS AND METHODS: This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. RESULTS: In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522). CONCLUSIONS: Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.
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Vitiligo , Humanos , Vitiligo/radioterapia , Vitiligo/terapia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adolescente , Lasers de Excimer/uso terapêutico , Lasers de Excimer/efeitos adversos , Adulto Jovem , CriançaRESUMO
Background: Traditional right hemicolectomy (TRH) is the standard treatment for patients with nonmetastatic right colon cancer. However, the ileocecum, a vital organ with mechanical and immune functions, is removed in these patients regardless of the tumor location. This study aimed to evaluate the technical and oncological safety of laparoscopic ileocecal-sparing right hemicolectomy (LISH). Method: Patients who underwent LISH at two tertiary medical centers were matched 1:2 with patients who underwent TRH by propensity score matching based on sex, age, body mass index, tumor location, and disease stage. Data on surgical and perioperative outcomes were collected. Oncological safety was evaluated in a specimen-oriented manner. Lymph nodes (LNs) near the ileocolic artery (ICA) were examined independently in the LISH group. Disease outcomes were recorded for patients who completed one year of follow-up. Results: In all, 34 patients in the LISH group and 68 patients in the TRH group were matched. LISH added 8 minutes to the dissection of LNs around the ileocolic vessels (groups 201/201d, 202, and 203 LNs), without affecting the total operation time, blood loss, or perioperative adverse event rate. Compared with TRH, LISH had a comparable lymphadenectomy quality, specimen quality, and safety margin while preserving a more functional bowel. The LISH group had no cases of LN metastasis near the ICA. No difference was detected in the recurrence rate at the 1-year follow-up time point between the two groups. Conclusion: In this dual-center study, LISH presented comparable surgical and oncological safety for patients with hepatic flexure or proximal transverse colon cancer.
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BACKGROUND: Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence. METHODS: Our analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method. RESULTS: Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris. CONCLUSION: Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.
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Emoções , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Personalidade , Psoríase , Humanos , Psoríase/psicologia , Psoríase/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. MicroRNAs (miRNAs) are an abundant class of non-coding RNA molecules. Recent studies have shown that multiple miRNAs are abnormally expressed in patients with psoriasis. The upregulation of miR-374a-5p has been associated with psoriasis severity. However, the specific role of miR-374a-5p in the pathogenesis of psoriasis remain unclear. METHODS: qRT-PCR was employed to validate the expression of miR-374a-5p in psoriatic lesions and in a psoriasis-like cell model constructed using a mixture of M5 (IL-17A, IL-22, OSM, IL-1α, and TNF-α). HaCaT cells were transfected with miR-374a-5p mimic/inhibitor, and assays including EdU, CCK-8, and flow cytometry were conducted to evaluate the effect of miR-374a-5p on cell proliferation. The expression of inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α was verified by qRT-PCR. Bioinformatics analysis and dual-luciferase reporter gene assay were performed to detect the downstream target genes and upstream transcription factors of miR-374a-5p, followed by validation of their expression through qRT-PCR and Western blotting. A psoriasis-like mouse model was established using imiquimod cream topical application. The psoriasis area and severity index scoring, hematoxylin-eosin histology staining, and Ki67 immunohistochemistry were employed to validate the effect of miR-374a-5p on the psoriatic inflammation phenotype after intradermal injection of miR-374a-5p agomir/NC. Additionally, the expression of pathway-related molecules and inflammatory factors such as IL-1ß, IL-17a, and TNF-α was verified by immunohistochemistry. RESULTS: Upregulation of miR-374a-5p was observed in psoriatic lesions and the psoriasis-like cell model. In vitro experiments demonstrated that miR-374a-5p not only promoted the proliferation of HaCaT cells but also upregulated the expression of inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α. Furthermore, miR-374a-5p promoted skin inflammation and epidermal thickening in the Imiquimod-induced psoriasis-like mouse model. Mechanistic studies revealed that miR-374a-5p led to downregulation of WIF1, thereby activating the Wnt5a/NF-κB signaling pathway. The transcription factor p65 encoded by RELA, as a subunit of NF-κB, further upregulated the expression of miR-374a-5p upon activation. This positive feedback loop promoted keratinocyte proliferation and abnormal inflammation, thereby facilitating the development of psoriasis. CONCLUSION: Our findings elucidate the role of miR-374a-5p upregulation in the pathogenesis of psoriasis through inhibition of WIF1 and activation of the Wnt5a/NF-κB pathway, providing new potential therapeutic targets for psoriasis.
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Proteínas Adaptadoras de Transdução de Sinal , MicroRNAs , NF-kappa B , Psoríase , Proteína Wnt-5a , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proliferação de Células , Regulação para Baixo , Células HaCaT , Imiquimode , MicroRNAs/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Psoríase/genética , Psoríase/patologia , Psoríase/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Regulação para Cima , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genéticaRESUMO
Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats.
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Depressão , Glicólise , Hipocampo , Transtornos da Memória , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Depressão/metabolismo , Depressão/tratamento farmacológico , Transtornos da Memória/metabolismo , Transtornos da Memória/tratamento farmacológico , Plasticidade Neuronal/efeitos dos fármacos , Eletrochoque , Estresse Psicológico/metabolismo , Estresse Psicológico/tratamento farmacológico , Modelos Animais de Doenças , Propofol/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
Nearly twenty-five percent of colorectal cancer (CRC) patients develop metachronous colorectal liver metastasis (CRLM) after curative surgery. Hepatosteatosis is the most prevalent liver condition worldwide, but its impact on the incidence of metachronous CRLM is understudied. In the present study, we aimed to investigate the predictive value of hepatic steatosis on the development of metachronous CRLM. First, a nested case-control study was conducted, enrolling stage I to III CRC patients in the National Colorectal Cancer Cohort (NCRCC) database. Metachronous CRLM patients and recurrence-free patients were matched via propensity-score matching. Fatty liver was identified based on treatment-naïve CT scans and the degree of hepatic fibrosis was scored. Multivariable analysis was conducted to investigate the association between fatty liver and metachronous CRLM. In our database, a total of 414 patients were included. Metachronous CRLM patients had considerably higher rates of hepatic steatosis (30.9% versus 15.9%, P<0.001) and highly fibrotic liver (11.6% versus 2.9%, P=0.001) compared to recurrence-free patients. Multivariable analysis showed that fatty liver (odds ratios [OR]=1.99, 95% confidence interval [CI] 1.19-3.30, P=0.008) and fibrotic liver (OR=4.27, 95% CI 1.54-11.81, P=0.005) were associated with high risk of metachronous CRLM. Further, a systematic literature review was performed to assess available evidence on the association between hepatosteatosis and development of metachronous CRLM. In the systematic review, 1815 patients were pooled from eligible studies, and hepatic steatosis remained a significant risk factor for metachronous CRLM (OR=1.90, 95% CI 1.35-2.66, P<0.001, I2=25.3%). In conclusion, our data suggest that patients with a steatotic liver and a high fibrosis score at CRC diagnosis have elevated risk of developing metachronous CRLM.
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Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m6A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm2 exhibited characteristics of photoaging. The m6A level of total RNA decreased in photoaged cells with a down-regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR-100-3p was a downstream target of METTL14. And METTL14 could affect pri-miR-100 processing to mature miR-100-3p in an m6A-dependent manner via DGCR8. Furthermore, miR-100-3p targeted at 3' end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR-100-3p inhibitor or overexpression of ERRFI1. In UVB-induced photoaging of human skin fibroblasts, METTL14-dependent m6A can regulate miR-100-3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR-100-3p/ERRFI1 axis.
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Fibroblastos , Metiltransferases , MicroRNAs , Envelhecimento da Pele , Raios Ultravioleta , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação , Metiltransferases/metabolismo , Metiltransferases/genética , Envelhecimento da Pele/efeitos da radiação , Envelhecimento da Pele/genética , Pele/metabolismo , Pele/efeitos da radiação , Adenosina/análogos & derivados , Adenosina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genéticaRESUMO
BACKGROUND: The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. RESULTS: The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1ß, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. CONCLUSIONS: This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.
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Colite Ulcerativa , Microbioma Gastrointestinal , Lactobacillus plantarum , Limosilactobacillus fermentum , Probióticos , Animais , Colite Ulcerativa/microbiologia , Colite Ulcerativa/prevenção & controle , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Camundongos , Probióticos/administração & dosagem , Probióticos/farmacologia , Masculino , Humanos , Sulfato de Dextrana/efeitos adversos , Colo/microbiologia , Colo/imunologia , Colo/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Mucina-2/metabolismo , Mucina-2/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-6/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Interferon gama/metabolismo , Interferon gama/genética , Interferon gama/imunologia , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Modelos Animais de DoençasRESUMO
Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models.
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Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Membrana , Animais , Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Bioensaio , Citosol , Imunidade Inata , Ligantes , Proteínas de Membrana/metabolismoRESUMO
This study aims to explore the preventive effects and underlying mechanisms of Lactobacillus fermentum CKCC1858 (CKCC1), L. fermentum CKCC1369 (CKCC2), Lactobacillus plantarum CKCC1312 (CKCC3), and Lactobacillus gasseri CKCC1913 (CKCC4) on high-fat diet combined with streptozotocin (HFD/STZ)-stimulated type 2 diabetes (T2D) in mice. Generally, the results indicated that most of the four probiotics reduced weight loss and liver and pancreas damage, significantly (p < 0.05) improved glucose metabolism by regulating glucagon-like peptide-1 (GLP-1), fasting glucose and insulin levels, and increasing expression of glucose transporters. Probiotics improved hyperlipemia, inflammation, and oxidative stress by reducing the secretion of blood lipids and proinflammatory cytokines, increasing antioxidant enzymes. Metagenomic results revealed that probiotics restored gut microbiota via enhancing (reducing) the relative abundance of beneficial bacteria (harmful bacteria) and altered specific metabolic pathways in T2D mice. CKCC1, CKCC3, and CKCC4 showed excellent effects compared to CKCC2. These results indicated that probiotics potentially prevented T2D, which is strain-specific.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Probióticos , Camundongos , Animais , Lactobacillus , Microbioma Gastrointestinal/fisiologia , Inflamação , Glucose , Dieta Hiperlipídica , Estresse Oxidativo , HomeostaseRESUMO
To investigate the effect of probiotic Lactobacillus fermentum CKCC1858, LF on the prevention of hyperlipidemia and its correlation with gut microbiota, golden hamsters were fed a high-fat diet alone or in combination with the probiotic for 6 weeks. The results showed that the LF intervention alleviated HFD-induced hyperlipidemia and liver damage, as evidenced by the reduced serum lipid profile levels and liver function markers. More importantly, the LF intervention attenuated HFD-induced microbiota dysbiosis by enhancing the abundance of SCFA-producing bacteria and reshaping the metabolic functions of the gut microbiota, likely contributing to its pronounced preventive effects on hyperlipidemia. This study elucidated the mechanism of the preventive effect of probiotics on hyperlipidemia in terms of regulating gut microbiota, and provided suggestions for regulating gut microbiota through probiotic interventions to improve lipid metabolism.
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Microbioma Gastrointestinal , Hiperlipidemias , Limosilactobacillus fermentum , Doenças Metabólicas , Cricetinae , Animais , Dieta Hiperlipídica/efeitos adversos , Mesocricetus , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologiaRESUMO
Extracellular vesicle (EV) therapy recently had shown significant efficacy in various diseases. Serum starvation culture (SC) is one of the most widely used methods for collecting EVs. However, SC may cause inadvertent effects and eventually dampen the therapeutic potential of EVs. Therefore, we developed a novel method for EV collection, continuous nutrient supply culture (CC), which can provide an optimal condition for mesenchymal stem cells (MSCs) by continuously supplying essential nutrients to MSCs. By comparing with SC strategy, we revealed that CC could maintain CC-MSCs in a normal autophagy and apoptotic state, which reduced the shunting of EV precursors in cells and useless information material carried by EVs. In CC-MSCs, the expression levels of endosomal sorting complexes required for transport (ESCRT) and targeting GTPase27 (Rab27) were upregulated compared to those in SC-MSCs. Besides, we analyzed the membrane transport efficiency of EV formation, which demonstrated the CC strategy could promote the formation of EV precursors and the release of EVs. In addition, miRNA analysis revealed that CC-EVs were enriched with anti-chronic inflammatory factors, which could inhibit the nuclear factor kappa-B (NF-κB) pathway, mitigate chronic inflammation, and effectively repair skin photo-aging damage.
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Malnutrition caused by insufficient nutritional supply may significantly hinder the quality of life among cancer patients. Sugar provides energy and nutritional support, but it also promotes cancer growth. Warburg effect is the reprogrammed glucose metabolic mode of cancer cells that meets the intensified ATP demand and biosynthesis. Vitamin C (VC) has anti-tumor effect. However, the relationship between cytotoxicity of VC on cancer cells and Warburg effect remains elusive, the effect of VC on glucose-induced oncogenic effect is also unclear. Based on colorectal cancer cell HCT116, our finding revealed that the discrepant oncogenic effect of different sugar is closely related to the intensification of Warburg effect, with glucose being the potent oncogenic component. Notably, as a potential Warburg effect inhibitor, VC suppressed cancer growth in a concentration-dependent manner and further reversed the glucose-induced oncogenic effect. Furthermore, VC protected tumor-bearing mice from insulin sensitivity impairment and inflammatory imbalance. These findings imply that VC might be a useful adjuvant treatment for cancer patients seeking to optimize nutritional support.
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Neoplasias Colorretais , Desnutrição , Animais , Camundongos , Ácido Ascórbico/farmacologia , Qualidade de Vida , Glucose , Neoplasias Colorretais/tratamento farmacológicoRESUMO
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by dysregulation of lipid metabolism, insulin resistance, and gut microbiota disorder. Compared to drug interventions, probiotic interventions may have a more enduring effect without producing any side effects. Thus, the potential of probiotics as a therapeutic approach for diabetes and other metabolic disorders has gained increasing attention in recent years. In this study, we evaluated the therapeutic efficacy of Lactobacillus gasseri CKCC1913, a potential probiotic strain, in high-fat diet-induced insulin-resistant diabetes using the C57BL/6J mouse animal model. From the results, L. gasseri CKCC1913 has been shown to increase glucose tolerance, reduce fasting blood glucose levels in diabetic mice, and reduce the expression of pro-inflammatory cytokines, such as TNF-α and IL-6. Besides, L. gasseri CKCC1913 intervention effectively alleviated oxidative stress damage by increasing SOD activity, decreasing MDA levels, reducing insulin resistance, and improving dyslipidemia caused by diabetes. The potential mechanism of L. gasseri CKCC1913 in improving metabolic health and alleviating diabetes involves an increased abundance of beneficial bacteria, such as Parabacteroides merdae, which directly produce short-chain fatty acids that help regulate immune cells and reduce inflammation. SCFAs also enter the bloodstream and promote antioxidant enzyme activity in the liver, protecting against oxidative damage. Additionally, L. gasseri CKCC1913 influences local bacterial metabolism pathways, such as the superpathway of unsaturated fatty acid biosynthesis, leading to an increase in unsaturated fatty acids, increasing high-density lipoprotein cholesterol (HDL-C) levels and improving lipid metabolism and glucose control in diabetic mice. In summary, in this study, L. gasseri CKCC1913 and its potential impact on metabolic health highlight the promising potential of probiotics as a therapeutic approach for diabetes. Future research should focus on identifying the optimal dose and duration, investigating the long-term effects and mechanisms of action, and exploring the potential use of probiotics as an adjunct to other therapies or in preventing metabolic disorders.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Lactobacillus gasseri , Animais , Camundongos , Camundongos Endogâmicos C57BL , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Experimental/terapia , Fígado , AntioxidantesRESUMO
Psoriasis is a chronic autoinflammatory skin disease associated with multiple comorbidities, with a prevalence ranging from 2 to 3% in the general population. Decades of preclinical and clinical studies have revealed that alterations in cholesterol and lipid metabolism are strongly associated with psoriasis. Cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-17), which are important in the pathogenesis of psoriasis, have been shown to affect cholesterol and lipid metabolism. Cholesterol metabolites and metabolic enzymes, on the other hand, influence not only the biofunction of keratinocytes (a primary type of cell in the epidermis) in psoriasis, but also the immune response and inflammation. However, the relationship between cholesterol metabolism and psoriasis has not been thoroughly reviewed. This review mainly focuses on cholesterol metabolism disturbances in psoriasis and their crosstalk with psoriatic inflammation.
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Citocinas , Psoríase , Humanos , Citocinas/metabolismo , Inflamação , Metabolismo dos Lipídeos , ColesterolRESUMO
Electroconvulsive shock (ECT) is the most effective treatment for depression but can impair learning and memory. ECT is increasingly being shown to activate astrocytes and induce neuroinflammation, resulting in cognitive decline. Activated astrocytes can differentiate into two subtypes, A1-type astrocytes and A2-type astrocytes. Regarding cognitive function, neurotoxic A1 astrocytes and neuroprotective A2 astrocytes may exhibit opposite effects. Specifically, prokineticin 2 (PK2) functions as an essential mediator of inflammation and induces a selective A2-protective phenotype in astrocytes. This study aimed to clarify how PK2 promotes improved learning memory following electroconvulsive shock (ECS). As part of the study, rats were modeled using chronic unpredictable mild stress. Behavioral experiments were conducted to assess their cognitive abilities and depression-like behaviors. Western blot was used to determine the expression of PK2. Immunohistochemical and electron microscopy analyses of the hippocampal CA1 region were conducted to study the activation of astrocyte subtypes and synaptic ultrastructure, respectively. In this study, rats' spatial learning and memory impairment began to improve as activated A1-subtype astrocytes gradually decreased, and PK2 and A2 phenotype activation peaked on the third day after ECS. PKRA7 (PK2 antagonist) inhibits A2-type astrocyte activation partially and suppresses spatial learning and memory improvement. Collectively, our findings support that PK2 may induce a selective modulation of astrocytic polarization to a protective phenotype to promote learning and memory improvement after ECS.
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Astrócitos , Depressão , Animais , Ratos , Astrócitos/metabolismo , Depressão/metabolismo , Eletrochoque/efeitos adversos , Eletrochoque/métodos , Aprendizagem , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismoRESUMO
[This corrects the article DOI: 10.1016/j.bioactmat.2021.07.030.].
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Background: Keloids are a fibroproliferative disease characterized by unsatisfactory therapeutic effects and a high recurrence rate. Objective: This study aimed to investigate keloid-related circulating metabolic signatures. Methods: Untargeted metabolomic analysis was performed to compare the metabolic features of 15 keloid patients with those of paired healthy volunteers in the discovery cohort. The circulating metabolic signatures were selected using the least absolute shrinkage. Furthermore, the selection operators were quantified using multiple reaction monitoring-based target metabolite detection methods in the training and test cohorts. Results: More than ten thousand metabolic features were consistently observed in all the plasma samples from the discovery cohort, and 30 significantly different metabolites were identified. Four differentially expressed metabolites including palmitoylcarnitine, sphingosine, phosphocholine, and phenylalanylisoleucine, were discovered to be related to keloid risk in the training and test cohorts. In addition, using linear and logistic regression models, the respective risk scores for keloids based on a 4-metabolite fingerprint classifier were established to distinguish keloids from healthy volunteers. Conclusions: In summary, our findings show that the characteristics of circulating metabolic fingerprinting manifest phenotypic variation in keloid onset.
Assuntos
Queloide , Humanos , Queloide/patologia , Modelos Logísticos , Palmitoilcarnitina/uso terapêutico , Fosforilcolina/uso terapêutico , EsfingosinaRESUMO
BACKGROUND: The Happiness Index Scale (HIS) is a newly developed scale by our group to screen for common psychological illnesses among general hospital inpatients. This study aimed to analyze the reliability, validity and screening effect of the HIS and to explore its clinical application. METHODS: From April 1, 2021, to December 31, 2021, a total of 8405 continuous inpatients were enrolled from different departments of a large tertiary general hospital with 1385 inpatient beds in Guangzhou, Guangdong Province, China. Using a cross-sectional survey design, each participant was assessed with the Patient Health Questionnaire 9(PHQ-9), Generalized Anxiety Disorder 7 items(GAD-7), Athens Insomnia Scale (AIS), Columbia Suicide Severity Rating Scale (C-SSRS) and HIS within 24 h of admission. McDonald's ω coefficient, the Guttman split-half coefficient and the test-retest reliability coefficient were used to evaluate the reliability of the HIS and the construct validity and criterion validity of the validity tests. Scores on the PHQ-9, GAD-7, AIS, and C-SSRS were used as the gold standard tools to analyze the screening effect of the HIS. RESULTS: The HIS exhibited very good reliability, with a McDonald's ω coefficient of 0.825, a Guttman split-half coefficient of 0.920 and a test-retest reliability coefficient of 0.745 (P < 0.05). Confirmatory factor analysis showed a satisfactory model fitting index with a χ2/df = 2.602, a root mean squared error of approximation (RMSEA) of 0.014, a standardized root mean square residual (SRMR) of 0.010, a comparative fit index (CFI) of 0.992, and a Tucker-Lewis index (TLI) of 0.983. The correlation coefficient between the total score of each dimension of the scale and the corresponding criterion was 0.854 ~ 0.949 (P < 0.001). The HIS showed a very good distinguishing effect. The average HIS score of inpatients who screened positive for psychological problems was significantly higher than that of inpatients who screened negative for psychological problems (t = 3790.619, P < 0.001). The effect size was very large (Cohens d = 2.695, 95% CI = 2.630 ~ 2.761). Approximately 90.2% of the positive and negative screening results of the HIS were matched with the gold standard tools, with a kappa value of 0.747 (P < 0.001). The screening effect test showed a sensitivity (true positive rate) of 92.9% and a specificity (true negative rate) of 89.5%. CONCLUSION: The HIS exhibited satisfactory reliability and validity and a clinically meaningful screening effect with a much shorter version compared to the commonly used screening scales. Thus, it could potentially be useful as the first screening step to rule out psychological conditions for inpatients in general hospitals or to remind medical teams of further psychological concerns.