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Diabetic peripheral neuropathy (DPN) is one of the strongest risk factors for diabetic foot ulcers (neuropathic ulcerations) and the existing ulcers may further deteriorate due to the damage to sensory neurons. Moreover, the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time. DPN is associated with gut microbiota dysbiosis. Traditional Chinese medicine (TCM) compounds such as Shenqi Dihuang Decoction, Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota. The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut mic-robiota.
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Insomnia, as one of the emotional diseases, has been increasing in recent years, which has a great impact on people's life and work. Therefore, researchers are eager to find a more perfect treatment. The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the treatment of insomnia, especially acupuncture and Chinese herbal medicine. It is the main method of TCM in the treatment of insomnia. This paper mainly reviews the combination degree of "microorganism-gut-brain axis" theory with TCM and acupuncture under the system of TCM. To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of "microorganism-gut-brain axis" theory, in order to provide a new idea for the diagnosis and treatment of insomnia.
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Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (â¢OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert â¢OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.
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Nanopartículas , Neoplasias , Camundongos , Animais , Lisossomos , Nanopartículas/química , Apoptose , AutofagiaRESUMO
With the progress and rapid societal development, women are confronted with multifaceted pressures in their lives, encompassing familial and other domains. Furthermore, during the perimenopausal phase, endocrine equilibrium is disrupted, leading to the emergence of psychological and physiological health challenges. Insomnia is a prevalent symptom among perimenopausal individuals. The brain-gut-bacteria axis assumes a pivotal role in the prevention, diagnosis, and management of perimenopausal insomnia. Chaihu Jia Longgu Muli decoction is a commonly prescribed remedy for addressing perimenopopausal insomnia. Consequently, this paper aims to investigate the interplay between the brain-gut-bacteria axis, intestinal microbiota, and the pathogenesis of perimenopausal insomnia. The study focuses on examining the regulatory effects of Chaihu Jia Longgu Muli decoction on the nervous system, intestinal microbiota, and the hypothalamus-pituitary-adrenal axis. Additionally, it explores the mechanisms underlying Hujia Longgu Muli decoction in mitigating perimenopausal insomnia.
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Medicamentos de Ervas Chinesas , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Perimenopausa , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Encéfalo , Medicina Tradicional Chinesa , IntestinosRESUMO
OBJECTIVE: To explore the active components and mechanism of Jiaotai Pill (JTP) in the treatment of primary insomnia (PI) based on gene expression omnibus. METHODS: The main active components of Jiaotai Pills were obtained by TCMSP and literature mining, and the targets of the active components of Jiaotai Pills were predicted. The targets were verified and standardized by Uniprot database. PI-related targets were obtained from GeneCards, OMIM, DrugBank, PharmGKB, and TTD databases. Obtaining an intersection action target point of the Jiaotai pill and the PI by using a Venny diagram; Gene chip data (GSE208668) was downloaded from gene expression omnibus database, and then gene probe enrichment analysis (GSEA) was used to screen the differentially expressed genes between PI patients and normal controls, and molecular docking was used to virtually verify the screened differentially expressed genes with potential active compounds. RESULTS: 21 active components and 263 potential targets of Jiaotai Pill were screened by database analysis and literature mining, 112 of which were intersected with PI. Molecular docking results showed that quercetin, EGCG, kaempferol, R-kanatin, stigmasterol, berberine and other core active components had good docking activity with related differential genes. CONCLUSION: Jiaotai Pill can regulate the release of inflammatory factors through multiple active ingredients, multiple disease targets, multiple biological pathways and multiple pathways to achieve the purpose of treating PI, which provides a theoretical basis for the clinical treatment of PI and broadens the clinical use of Jiaotai Pill.
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Berberina , Distúrbios do Início e da Manutenção do Sono , Humanos , Farmacologia em Rede , Simulação de Acoplamento Molecular , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/genéticaRESUMO
Simultaneous lactate metabolism inhibition and intracellular acidification (LIIA) is a promising approach for inducing tumor regression by depleting ATP. However, given the limited efficacy of individual metabolic modulators, a combination of various modulators is required for highly efficient LIIA. Herein, a co-delivery system that combines lactate transporter inhibitor, glucose oxidase, and O2 -evolving nanoparticles is proposed. As a vehicle, a facile room-temperature synthetic method for large-pore mesoporous silica nanoparticles (L-MSNs) is developed. O2 -evolving nanoparticles are then conjugated onto L-MSNs, followed by immobilizing the lactate transporter inhibitor and glucose oxidase inside the pores of L-MSNs. To load the lactate transporter inhibitor, which is too small to be directly loaded into the large pores, it is encapsulated in albumin by controlling the albumin conformation before being loaded into L-MSNs. Notably, inhibiting lactate efflux shifts the glucose consumption mechanism from lactate metabolism to glucose oxidase reaction, which eliminates glucose and produces acid. This leads to synergistic LIIA and subsequent ATP depletion in cancer cells. Consequently, L-MSN-based co-delivery of modulators for LIIA shows high anticancer efficacy in several mouse tumor models without toxicity in normal tissues. This study provides new insights into co-delivery of small-molecule drugs, proteins, and nanoparticles for synergistic metabolic modulation in tumors.
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Nanopartículas , Neoplasias , Animais , Camundongos , Glucose Oxidase/uso terapêutico , Transportadores de Ácidos Monocarboxílicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/uso terapêutico , Glucose , Concentração de Íons de Hidrogênio , Trifosfato de Adenosina , Albuminas , Dióxido de Silício , Porosidade , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/uso terapêuticoRESUMO
BACKGROUND: The efficacy of traditional Chinese exercise (TCE)-based intervention in the improvement of anthropometric and biochemical indicators in overweight and obese patients is controversial. In this regard, the aim of this review was to summarize the evidence of TCE interventions to evaluate their effectiveness on the anthropometric and biochemical indicators of overweight and obese patients. METHOD: Five databases were systematically searched for relevant articles published from inception to October 2022. Randomized controlled trials examining TCE intervention in overweight and obese patients The treatment effects were estimated using a random-effect meta-analysis model with standardized mean differences (Hedges' g). The categorical and continuous variables were used to conduct moderator analyses. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (identifier CRD42022377632). RESULT: Nine studies involving a total of 1297 participants were included in the final analysis. In the anthropometric indicators outcomes, the meta-analytic findings revealed large and significant improvements in body mass index (g = 1.44, 95% confidence interval [CI] = 1.27-1.61, P = .000, I2 = 99%), weight (g = 1.47, 95% CI = 1.25-1.68, P = .000, I2 = 95%), fat percentage (g = 1.22, 95% CI = 0.52-1.93, P = .000, I2 = 93%), and small and significant improvements in waist circumference (g = 0.38, 95% CI = 0.21-0.54, P = .000, I2 = 99%). In the biochemical indicators outcomes, the findings revealed large and significant improvements in low density lipoprotein (g = 2.08, 95% CI = 1.80-2.37, P = .000, I2 = 98%), moderate and significant improvements in triglyceride (g = 0.69, 95% CI = 0.56-0.81, P = .000, I2 = 96%), small and significant improvements in total cholesterol (g = 0.37, 95% CI = 0.19-0.54, P = .000, I2 = 77%), and high-density lipoprotein (g = -0.71, 95% CI = -0.86 to 0.57, P = .000, I2 = 99%). The moderator shows that the effects of TCE on anthropometric and biochemical indicators were moderated by frequency of exercise, exercise duration, and type of control group. CONCLUSION: TCE intervention is a beneficial non-pharmacological approach to improving anthropometric and biochemical indicators in overweight and obese subjects, especially in body mass index, weight, fat percentage, triglyceride, and low-density lipoprotein. The clinical relevance of our findings is pending more extensive trials and more rigorous study designs to strengthen the evidence.
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Terapia por Exercício , Obesidade , Sobrepeso , Humanos , Obesidade/terapia , Sobrepeso/terapiaRESUMO
Breast cancer (BRCA) remains the most prevalent cancer worldwide and the tumor microenvironment (TME) has been discovered to exert a wide influence on the overall survival and therapeutic response. Numerous lines of evidence reported that the effects of immunotherapy of BRCA were manipulated by TME. Immunogenic cell death (ICD) is a form of regulated cell death (RCD) that is capable of fueling adaptive immune responses and aberrant expression of ICD-related genes (ICDRGs) can govern the TME system by emitting danger signals or damage-associated molecular patterns (DAMPs). In the current study, we obtained 34 key ICDRGs in BRCA. Subsequently, using the transcriptome data of BRCA from the TCGA database, we constructed a risk signature based on 6 vital ICDRGs, which had a good performance in predicting the overall survival of BRCA patients. We also examined the efficacy of our risk signature in the validation dataset (GSE20711) in the GEO database and it performed excellently. According to the risk model, patients with BRCA were divided into high-risk and low-risk groups. Also, the unique immune characteristics and TME between the two subgroups and 10 promising small molecule drugs targeting BRCA patients with different ICDRGs risk have been investigated. The low-risk group had good immunity indicated by T cell infiltration and high immune checkpoint expression. Moreover, the BRCA samples could be divided into three immune subtypes according to immune response severity (ISA, ISB, and ISC). ISA and ISB predominated in the low-risk group and patients in the low-risk group exhibited a more vigorous immune response. In conclusion, we developed an ICDRGs-based risk signature that can predict the prognosis of BRCA patients and offer a novel therapeutic strategy for immunotherapy, which would be of great significance in the BRCA clinical setting.
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OBJECTIVE: To demonstrate the value of Internet of things (IoT)-based diagnosis-treatment model in improving medical service quality during the novel coronavirus pneumonia (COVID-19) outbreak. METHODS: In this retrospective analysis, 483 patients with chronic diseases treated between January 2020 and March 2021 were selected and grouped as follows based on different intervention methods: a research group (the Res group) with 229 patients that were given IoT-based diagnosis and treatment, and a control group (the Con group) with 254 patients that were treated with routine diagnosis and treatment. The qualified rate of medical records, the missing rate of medical records, and the incidence of doctor-patient disputes were compared between the two groups. In addition, investigations were made regarding patients' daily living ability, psychological state, health behavior, self-care ability, quality of life, as well as treatment satisfaction. RESULTS: There was no difference in the qualified rate of medical records between the Res group and the Con group (P>0.05), but the missing rate of medical records and the incidence of doctor-patient disputes were lower in the Res group (both P<0.05). An obviously improved living ability was observed in both groups after the treatment (both P<0.05), with no statistical significance between groups (P>0.05). Besides, the Res group presented lower scores of SAS and SDS but higher scores of SRAHP, ES-CA and SF-36 than the Con group after treatment (all P<0.05). Finally, according to the satisfaction survey, more patients in the Res group were very satisfied but fewer cases were dissatisfied with the medical service they received as compared with the Con group (both P<0.05). CONCLUSIONS: The IoT-based diagnosis-treatment model can effectively improve the quality of medical services and patients' self-care ability, which is extremely important and promising for addressing the current medical limitations during the COVID-19 epidemic.
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Diabetic peripheral neuropathy (DPN) is the most common neuropathy in the world, mainly manifested as bilateral symmetry numbness, pain or paresthesia, with a high rate of disability and mortality. Schwann cells (SCs), derived from neural ridge cells, are the largest number of glial cells in the peripheral nervous system, and play an important role in DPN. Studies have found that SCs are closely related to the pathogenesis of DPN, such as oxidative stress, endoplasmic reticulum stress, inflammation, impaired neurotrophic support and dyslipidemia. This article reviews the mechanism of SCs in DPN.
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Diabetes Mellitus , Neuropatias Diabéticas , Humanos , Estresse Oxidativo , Células de Schwann/patologia , Neuroglia/patologia , Diabetes Mellitus/patologiaRESUMO
OBJECTIVE: To explore the curative effect of "Jiaotai Pill" combined with head rhythmic massage consistent with 5-tone rhythm on insomnia of heart-kidney disharmony type. METHODS: Sixty patients with insomnia in massage clinic and ward were randomly divided into treatment group A (30 cases) and treatment group B (30 cases). Patients in group A were treated with traditional head massage combined with oral estazolam tablets. Group B was treated with "Jiaotai Pill" combined with head rhythmic massage therapy consistent with 5-tone rhythm. After 2 weeks of treatment, the scores of Hamilton Anxiety Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index and Traditional Chinese Medicine Symptom Scale, as well as the expression changes of interleukin (IL)-6 and IL-8 in serum were compared between the 2 groups before and after treatment. RESULTS: After 2 weeks of treatment, the total effective rate of group B was 93. 33%, which was significantly higher than that of group A (66. 67%) (P < .05). After treatment, the scores of Hamilton Anxiety Scale, PQSI, insomnia severity index and traditional Chinese medicine symptom scores were significantly decreased in both groups, and the decrease in group B was more significant than that in group A (P < .05). After treatment, the serum levels of IL-6 and IL-8 were significantly decreased in both groups, and the decrease in group B was greater than that in group A, the difference was statistically significant (P < .05). CONCLUSION: The overall efficacy of Jiaotai Pill combined with head massage therapy consistent with 5-tone rhythm is significantly better than that of traditional massage combined with 5-element music therapy for insomnia patients with heart-kidney disharmony.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Interleucina-8 , Rim , Massagem , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do TratamentoRESUMO
Restless leg syndrome (Restless legs syndrome, RLS) is a common neurological disorder. The pathogenesis of RLS remains unknown, and recent pathophysiological developments have shown the contribution of various genetic markers, neurotransmitter dysfunction, and iron deficiency to the disease, as well as other unidentified contributing mechanisms, particularly chronic renal dysfunction. RLS enhancement syndrome is frequently observed in patients with RLS who have received long-term dopamine agonist therapy, manifesting as a worsening of RLS symptoms, usually associated with an increase in the dose of dopamine agonist. Some patients with RLS can adequately control their symptoms with non-pharmacological measures such as massage and warm baths. First-line treatment options include iron supplementation for those with evidence of reduced iron stores, or gabapentin or pregabalin, as well as dopamine agonists, such as pramipexole. Second-line therapies include opioids such as tramadol. RLS seriously affects the quality of life of patients, and because its pathogenesis is unclear, more biological evidence and treatment methods need to be explored.
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Agonistas de Dopamina , Síndrome das Pernas Inquietas , Humanos , Agonistas de Dopamina/uso terapêutico , Síndrome das Pernas Inquietas/tratamento farmacológico , Síndrome das Pernas Inquietas/diagnóstico , Qualidade de Vida , Gabapentina/uso terapêutico , Ferro/uso terapêuticoRESUMO
Breast cancer is becoming a common life-threatening disease, especially in women, along with higher incidence and mortality. MicroRNA (miR)-506 was reported to participate in breast cancer progression, while the role of miR-506 in breast cancer-induced osteolytic bone metastasis is unclear. In the present study, we found significant downregulation of miR-506 in breast cancer tissues and cell lines. Overexpression of miR-506 notably reduced the proliferative, migratory and invasive rates of MCF7 and MDA-MB-231 cells, and reduced the production of inflammatory factors IL-6 and TNF-α in MCF7 cells. Moreover, overexpression of miR-506 obviously inhibited tumor growth in an in vivo animal model. In addition, overexpression of miR-560 efficiently attenuated breast cancer-induced osteolysis in vivo, which was characterized by increased bone volume/total volume (BT/TV), trabecular number (Tb. N), and trabecular thickness (Tb. Th), as well as the reduced trabecular separation (Tb. Sp). The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) was identified as a downstream target of miR-506, and overexpression of miR-506 could inhibit breast cancer progression by targeting NFATc1. Furthermore, our results showed that NFATc-1 might participate in the inhibition of miR-506 on breast cancer-induced osteolysis. In conclusion, our findings provide insights into understanding the pathogenesis of breast cancer and breast cancer-induced osteolytic bone metastasis, and miR-506 might serve as a novel biomarker for this disease.
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Neoplasias Ósseas , MicroRNAs , Osteólise , Animais , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Feminino , Interleucina-6 , MicroRNAs/genética , MicroRNAs/metabolismo , Osteólise/etiologia , Osteólise/metabolismo , Osteólise/patologia , Transdução de Sinais , Fatores de Transcrição , Fator de Necrose Tumoral alfaRESUMO
Due to concealed initial symptoms, many diabetic patients are not diagnosed in time, which delays treatment. Machine learning methods have been applied to increase the diagnosis rate, but most of them are black boxes lacking interpretability. Rule extraction is usually used to turn on the black box. As the number of diabetic patients is far less than that of healthy people, the rules obtained by the existing rule extraction methods tend to identify healthy people rather than diabetic patients. To address the problem, a method for extracting reduced rules based on biased random forest and fuzzy support vector machine is proposed. Biased random forest uses the k-nearest neighbor (k-NN) algorithm to identify critical samples and generates more trees that tend to diagnose diabetes based on critical samples to improve the tendency of the generated rules for diabetic patients. In addition, the conditions and rules are reduced based on the error rate and coverage rate to enhance interpretability. Experiments on the Diabetes Medical Examination Data collected by Beijing Hospital (DMED-BH) dataset demonstrate that the proposed approach has outstanding results (MCC = 0.8802) when the rules are similar in number. Moreover, experiments on the Pima Indian Diabetes (PID) and China Health and Nutrition Survey (CHNS) datasets prove the generalization of the proposed method.
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Diabetes Mellitus , Máquina de Vetores de Suporte , Algoritmos , Diabetes Mellitus/diagnóstico , Diagnóstico Precoce , Humanos , Aprendizado de MáquinaRESUMO
Lymph node metastasis is a key factor of death and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Previous studies have demonstrated that Cystathionine-ß-synthase (CBS)/H2S system plays important roles in progression of various cancer. However, the function and mechanism of CBS/H2S system in lymph node metastasis of ESCC remains unclear. Here, we found that CBS was highly expressed in human ESCC tissues and closely associated with lymph node metastasis in ESCC patients. Functional studies demonstrated that CBS could significantly promote lymph node metastasis of ESCC tumor cells. In vitro, CBS knockdown inhibited tumor cell proliferation, migration and invasion, whereas CBS overexpression produced the opposite results. In vivo, downregulation of CBS distinctly inhibited ESCC tumor growth and lymphatic metastasis, as evidenced by the decreased size and weight of tumor and popliteal lymph node. Meanwhile, we also found high expression of CBS-induced ESCC angiogenesis and lymphangiogenesis in vitro and in vivo by upregulating VEGF, VEGF-C, and VEGF-D. Mechanistically, CBS up-regulated the expression of SIRT1 and thus interrupted the Notch1/Hes1 axis, which plays a crucial role in lymph node metastasis of ESCC. Moreover, it was demonstrated that H2S derived from CBS-activated SIRT1 via increasing the NAD+/NADH ratio and promoting the phosphorylation of SIRT1. In addition, H2S derived from CBS also enhanced SIRT1 protein stability. Taken together, these data show that the high expression of CBS/H2S system promotes ESCC lymph node metastasis via activating SIRT1 signaling pathway and CBS could serve as a potential therapeutic target for clinical intervention in ESCC.
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Cistationina beta-Sintase , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Sirtuína 1 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurodegeneration, nerve loss, neurofibrillary tangles, and Aß plaques. In modern medical science, there has been a serious obstacle to the effective treatment of AD. At present, there is no clinically proven and effective western medicine treatment for AD. The reason is that the etiology of AD is not yet fully understood. In 2018, the international community put forward a purely biological definition of AD, but soon this view of biomarkers was widely questioned, because the so-called AD biomarkers are shared with other neurological diseases, the diagnostic accuracy is low, and they face various challenges in the process of clinical diagnosis and treatment. Nowadays, scholars increasingly regard AD as the result of multimechanism and multicenter interaction. Because there is no exact Western medicine treatment for AD, the times call for the comprehensive treatment of AD in traditional Chinese medicine (TCM). AD belongs to the category of "dull disease" in TCM. For thousands of years, TCM has accumulated a lot of relevant treatment experience in the process of diagnosis and treatment. TCM, acupuncture, and the combination of acupuncture and medicine all play an important role in the treatment of AD. Based on the research progress of modern medicine on the pathophysiology of AD, this paper discusses the treatment of this disease with the combination of acupuncture and medicine.
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Terapia por Acupuntura , Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Biomarcadores , Medicina Tradicional ChinesaRESUMO
Narcolepsy is a relatively rare brain disorder caused by the selective loss of orexin neurons. Narcolepsy is divided into Narcolepsy Type 1 (NT1) and Narcolepsis Type 2 (NT2). The pathogenesis of NT1 has been well established due to the severe loss of orexin neurons, while NT2 is still poorly understood, and little is known about its underlying neurobiological mechanisms. human leukocyte antigen alleles have been found to strongly influence the development of narcolepsy, with more than 90% of NT1 patients carrying the human leukocyte antigen II allele DQB1*06:02. In addition to the genetic evidence for the DQBI*06:02 allele, some other evidence suggests that a T cell-mediated immune mechanism destroys the orexin neurons of NT1, with CD4â +â T cells being key. For this disease, traditional Chinese medicine (TCM) therapy has its own characteristics and advantages, especially the combination of acupuncture and medicine in the treatment of this disease in TCM, which has made considerable and gratifying progress. The purpose of this review is to introduce the frontier progress of neurobiology of narcolepsy, and to explore the syndrome differentiation and treatment of narcolepsy with the combined use of TCM and Western medicine combined with TCM.
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Medicina Tradicional Chinesa , Narcolepsia , Humanos , Orexinas/metabolismo , Medicina Tradicional Chinesa/efeitos adversos , Narcolepsia/diagnóstico , Narcolepsia/terapia , Narcolepsia/etiologia , Encéfalo/metabolismo , Antígenos HLARESUMO
BACKGROUND: Coronary heart disease (CHD) seriously affects human health, and its pathogenesis is closely related to atherosclerosis. The Huzhang (the root of Polygonum cuspidatum)-Shanzha (the fruit of Crataegus sp.), a classic herb pair, has been widely used for the treatment of CHD. In recent years, Huzhang-Shanzha herb pair (HSHP) was found to have a wide range of effects in CHD; however, its therapeutic specific mechanisms remain to be further explored. The aim of this study was to elucidate the molecular mechanism of HSHP in the treatment of CHD using a network pharmacology analysis approach. METHODS: The Batman-TCM database was used to explore bioactive compounds and corresponding targets of HSHP. CHD disease targets were extracted from Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Then, the protein-protein interaction (PPI) network was constructed using the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Finally, molecular docking of the active components was assessed to verify the potential targets of HSHP to treat CHD by the AutoDock Vina and PyMOL software. RESULTS: Totally, 243 active components and 2459 corresponding targets of LDP were screened out. Eighty-five common targets of HSHP and CHD were identified. The results of the network analysis showed that resveratrol, anthranone, emodin, and ursolic acid could be defined as four therapeutic components. TNF, ESR1, NFÐB1, PPARG, INS, TP53, NFÐBIA, AR, PIK3R1, PIK3CA, PTGS2, and NR3C1 might be the 12 key targets. These targets were mainly involved in the regulation of biological processes, such as inflammatory responses and lipid metabolism. Enrichment analysis showed that the identified genes were mainly involved in fluid shear force, insulin resistance (IR), inflammation, and lipid metabolism pathways to contribute to CHD. This suggests that resveratrol, anthranone, emodin, and ursolic acid from HSHP can be the main therapeutic components of atherosclerosis. CONCLUSION: Using network pharmacology, we provide new clues on the potential mechanism of action of HSHP in the treatment of CHD, which may be closely related to the fluid shear force, lipid metabolism, and inflammatory response.
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Dandelion, a medicinal and edible plant, exhibits anti-inflammatory activity. The purpose of the present study was to investigate the inhibitory effectiveness of the aqueous dandelion root extract (DRE) on esophageal squamous cell carcinoma (ESCC). The in vitro cell proliferation, migration, invasion and apoptosis and the in vivo tumor growth were evaluated. The effects of DRE on PI3K/Akt and Ras/Raf/ERK pathways, which are important signaling pathways related to the development and progression of esophageal squamous cell carcinoma, were studied. The effects of DRE on the expression of apoptosis-related proteins BCL2 and BAX were also investigated. Meanwhile, the role of a cystathionine-ß-synthase (CBS)/H2S system in ESCC cells and the effects of DRE on the CBS/H2S system were assessed. The results showed that DRE selectively inhibited cell growth, proliferation, migration and invasion and induced cell apoptosis in ESCC cells. Moreover, the oral administration of DRE retarded the growth of tumors in human ESCC xenograft models. The DRE treatment led to a dose-dependent reduction in the levels of PI3K, p-Akt, Ras, Raf and pERK1/2 proteins in ESCC cells. DRE also caused a decrease in the anti-apoptotic protein BCL2 and an increase in the pro-apoptotic protein BAX. The data also showed that the CBS/H2S system implicated in the process of ESCC and DRE inhibited the CBS/H2S system. Moreover, the CBS knockdown weakened the cancer cell-inhibiting effectiveness of DRE. Therefore, DRE may affect ESCC progression through the regulation of PI3K/Akt and Ras/Raf/ERK signal pathways as well as the endogenous CBS/H2S system, and consequently, serve as an effective anti-cancer alternative for human ESCC treatment.