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1.
Int J Biol Macromol ; 274(Pt 1): 133171, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38880444

ABSTRACT

Cancer treatment faces numerous challenges, such as inadequate drug targeting, steep price tags, grave toxic side effects, and limited therapeutic efficacy. Therefore, there is an urgent need for a safe and effective new drug to combat cancer. Microbial polysaccharides, complex and diverse biological macromolecules, exhibit significant microbial variability and uniqueness. Studies have shown that terrestrial microbial polysaccharides possess a wide range of biological activities, including immune enhancement, antioxidant properties, antiviral effects, anti-tumour potential, and hypoglycemic functions. To delve deeper into the structure-activity relationship of these land-based microbial polysaccharides against cancer, we conducted a comprehensive review and analysis of anti-cancer literature published between 2020 and 2024. The anticancer efficacy of terrestrial microbial polysaccharides is influenced by multiple factors, including the microbial species, existing form, chemical structure, and polysaccharide purity. According to the literature, an optimal molecular weight and good water solubility are essential for demonstrating anticancer activity. Furthermore, the addition of mannose and galactose has been found to significantly enhance the anticancer properties of these polysaccharides. These insights will serve as a valuable reference for future research and progress in the field of cancer drug therapy, particularly with regards to terrestrial microbial polysaccharides.

2.
J Ethnopharmacol ; 330: 118179, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38636575

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a typical chronic microvascular complication of diabetes, characterized by proteinuria and a gradual decline in renal function. At present, there are limited clinical interventions aimed at preventing the progression of DN to end-stage renal disease (ESRD). However, Chinese herbal medicine presents a distinct therapeutic approach that can be effectively combined with conventional Western medicine treatments to safeguard renal function. This combination holds considerable practical implications for the treatment of DN. AIM OF THE STUDY: This review covers commonly used Chinese herbal remedies and decoctions applicable to various types of DN, and we summarize the role played by their active ingredients in the treatment of DN and their mechanisms, which includes how they might improve inflammation and metabolic abnormalities to provide new ideas to cope with the development of DN. MATERIALS AND METHODS: With the keywords "diabetic nephropathy," "Chinese herbal medicine," "clinical effectiveness," and "bioactive components," we conducted an extensive literature search of several databases, including PubMed, Web of Science, CNKI, and Wanfang database, to discover studies on herbal formulas that were effective in slowing the progression of DN. The names of the plants covered in the review have been checked at MPNS (http://mpns.kew.org). RESULTS: This review demonstrates the superior total clinical effective rate of combining Chinese herbal medicines with Western medicines over the use of Western medicines alone, as evidenced by summarizing the results of several clinical trials. Furthermore, the review highlights the nephroprotective effects of seven frequently used herbs exerting beneficial effects such as podocyte repair, anti-fibrosis of renal tissues, and regulation of glucose and lipid metabolism through multiple signaling pathways in the treatment of DN. CONCLUSIONS: The potential of herbs in treating DN is evident from their excellent effectiveness and the ability of different herbs to target various symptoms of the condition. However, limitations arise from the deficiencies in interfacing with objective bioindicators, which hinder the integration of herbal therapies into modern medical practice. Further research is warranted to address these limitations and enhance the compatibility of herbal therapies with contemporary medical standards.


Subject(s)
Diabetic Nephropathies , Drugs, Chinese Herbal , Diabetic Nephropathies/drug therapy , Humans , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Animals , Medicine, Chinese Traditional/methods , Phytotherapy
3.
J Tradit Chin Med ; 44(2): 334-344, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38504539

ABSTRACT

OBJECTIVE: To explore the mechanism of Dangua Fang (, DGR) in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics. METHODS: Sprague-Dawley rats with normal glucose levels were randomly divided into three groups, including a conventional diet control group (Group A), high-fat-high-sugar diet model group (Group B), and DGR group (Group C, high-fat-high-sugar diet containing 20.5 g DGR). After 10 weeks of intervention, the fasting blood glucose (FBG), 2 h blood glucose [PBG; using the oral glucose tolerance test (OGTT)], hemoglobin A1c (HbA1c), plasma total cholesterol (TC), and triglycerides (TG) were tested, and the livers of rats were removed to calculate the liver index. Then, hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis followed by database search and bioinformatics analysis. Finally, cell experiments were used to verify the results of phosphoproteomics. Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4 (MAP4k4) and phosphorylated adducin 1 (ADD1) were detected using western blotting. RESULTS: DGR effectively reduced PBG, TG, and the liver index (P < 0.05), and significantly decreased HbA1c, TC, and hepatic portal TG (P < 0.01), showed significant hematoxylin and eosin (HE) staining, red oil O staining, and Masson staining of liver tissue. The total spectrum was 805 334, matched spectrum was 260 471, accounting for accounting 32.3%, peptides were 19 995, modified peptides were 14 671, identified proteins were 4601, quantifiable proteins were 4417, identified sites were 15 749, and quantified sites were 14659. Based on the threshold of expression fold change ( > 1.2), DGR up-regulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins, and down-regulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins, which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism. Therefore, DGR improved biological tissue processes, including information storage and processing, cellular processes and signaling, and metabolism. The metabolic functions regulated by DGR mainly include energy production and conversion, carbohydrate transport and metabolism, lipid transport and metabolism, inorganic ion transport and metabolism, secondary metabolite biosynthesis, transport, and catabolism. In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies. CONCLUSION: DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders, thereby regulating glycolipid metabolism through a multi-target and multi-method process.


Subject(s)
Blood Glucose , Tandem Mass Spectrometry , Rats , Animals , Rats, Sprague-Dawley , Blood Glucose/metabolism , Glycated Hemoglobin , Chromatography, Liquid , Liver , Lipid Metabolism , Glycolipids/metabolism , Glycolipids/pharmacology , Triglycerides/metabolism , Peptides/metabolism , Peptides/pharmacology , Diet, High-Fat
4.
Biomed Pharmacother ; 172: 116261, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38340397

ABSTRACT

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with a pathogenesis that remains incompletely understood, resulting in limited treatment options. MCC950, a highly specific NLRP3 inflammasome inhibitor, effectively suppresses the activation of NLRP3, thus reducing the production of caspase-1, the pro-inflammatory cytokines IL-1ß and IL-18. This review highlights the pivotal role of NLRP3 inflammasome activation pathways in the pathogenesis of SLE and discusses the potential therapeutic application of MCC950 in SLE. Notably, it comprehensively elucidates the mechanism of MCC950 targeting the NLRP3 pathway in SLE treatment, outlining its potential role in regulating autophagy and necroptosis. The insights gained contribute to a deeper understanding of the value of MCC950 in SLE therapy, serving as a robust foundation for further research and potential clinical applications.


Subject(s)
Autoimmune Diseases , Indenes , Lupus Erythematosus, Systemic , Humans , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Lupus Erythematosus, Systemic/drug therapy , Furans/therapeutic use , Indenes/therapeutic use , Sulfonamides
5.
Int J Biol Macromol ; 262(Pt 1): 129846, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38296150

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder influenced by various factors, including age, genetics, and the environment. Current treatments provide symptomatic relief without impeding disease progression. Previous studies have demonstrated the therapeutic potential of exogenous heparin and chondroitin sulfate in PD. However, their therapeutic mechanisms and structure-activity relationships remain poorly understood. In this study, low-molecular-weight heparin (L-HP) and chondroitin sulfate (L-CS) exhibited favorable therapeutic effects in a mouse model of PD. Proteomics revealed that L-HP attenuated mitochondrial dysfunction through its antioxidant properties, whereas L-CS suppressed neuroinflammation by inhibiting platelet activation. Two glycosaminoglycan (GAG)-binding proteins, manganese superoxide dismutase (MnSOD2) and fibrinogen beta chain (FGB), were identified as potential targets of L-HP and L-CS, and we investigated their structure-activity relationships. The IdoA2S-GlcNS6S/GlcNAc6S unit in HP bound to SOD2, whereas the GlcA-GalNAc4S and GlcA-GalNAc4S6S units in CS preferred FGB. Furthermore, N-S and 2-O-S in L-HP, and 4-O-S, 6-O-S, and -COOH in L-CS contributed significantly to the binding process. These findings provide new insights and evidence for the development and use of glycosaminoglycan-based therapeutics for PD.


Subject(s)
Chondroitin Sulfates , Parkinson Disease , Animals , Mice , Chondroitin Sulfates/pharmacology , Chondroitin Sulfates/therapeutic use , Chondroitin Sulfates/chemistry , Heparin, Low-Molecular-Weight/pharmacology , Heparin, Low-Molecular-Weight/therapeutic use , Parkinson Disease/drug therapy , Glycosaminoglycans/pharmacology , Glycosaminoglycans/chemistry , Heparin
6.
Biomed Pharmacother ; 170: 116033, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38128181

ABSTRACT

Although stem cell transplantation is an effective strategy in the treatment of type 1 diabetes mellitus (T1DM), the mechanisms underlying its therapeutic effects remain unclear. We hypothesized that stem cells target gut microbiota and intestinal mucosal immunity to promote therapeutic effects against T1DM. We investigated the effects of human amniotic mesenchymal stem cells (hAMSCs) on intestinal microbiota and mucosal immunity in streptozotocin-induced T1DM mice. hAMSCs promoted significant reductions in blood glucose levels and increased the number of insulin-secreting cells in the T1DM model. Compared with T1DM model mice, 16S rRNA sequencing revealed significant differences in the composition, diversity, and abundance of microbiota in the ileum of hAMSC-treated mice. Bifidobacterium, Prevotella, and Alcaligenes species were among the 15 most abundant differential bacterial species. LC-MS revealed significant changes in ileal metabolites, and among the top 100 differential metabolites identified, we found that a significant increase in taurine was closely associated with hAMSC therapy. Additionally, we detected significant differences between the two groups with respect to the frequency and phenotype of CD4+ T cell subsets in mesenteric lymph nodes, and hAMSCs promoted significant increases in Th2 and Treg cell frequencies and reduced the frequencies of Th1 and Th17 cells. Moreover, correlation analysis revealed pairwise correlations between differential microflora and differential metabolites and immune signatures. hAMSCs thus have positive effects on the microbiota and their metabolites in the ileum and intestinal mucosal immunity in T1DM. Our findings indicate that gut microbiota and intestinal mucosal immunity may play vital roles in the hAMSC-based treatment of T1DM.


Subject(s)
Diabetes Mellitus, Type 1 , Gastrointestinal Microbiome , Humans , Mice , Animals , RNA, Ribosomal, 16S , Stem Cell Transplantation
7.
J Nanobiotechnology ; 21(1): 374, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37833748

ABSTRACT

Anaplastic thyroid cancer (ATC) is a rare but highly aggressive kind of thyroid cancer. Various therapeutic methods have been considered for the treatment of ATC, but its prognosis remains poor. With the advent of the nanomedicine era, the use of nanotechnology has been introduced in the treatment of various cancers and has shown great potential and broad prospects in ATC treatment. The current review meticulously describes and summarizes the research progress of various nanomedicine-based therapeutic methods of ATC, including chemotherapy, differentiation therapy, radioiodine therapy, gene therapy, targeted therapy, photothermal therapy, and combination therapy. Furthermore, potential future challenges and opportunities for the currently developed nanomedicines for ATC treatment are discussed. As far as we know, there are few reviews focusing on the nanomedicine of ATC therapy, and it is believed that this review will generate widespread interest from researchers in a variety of fields to further expedite preclinical research and clinical translation of ATC nanomedicines.


Subject(s)
Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Humans , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/genetics , Iodine Radioisotopes , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/genetics , Combined Modality Therapy , Prognosis
8.
Int J Biol Macromol ; 251: 126317, 2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37595705

ABSTRACT

In this study, we systematically collected relevant literature in the past five years on the intervention of natural polysaccharides in alcoholic liver disease (ALD) and reviewed the pharmacological activities and potential mechanisms of action. Natural polysaccharides are effective in preventing liver tissue degeneration, inhibiting the alcohol-induced expression of inflammatory factors, inactivation of antioxidant enzymes, and abnormal hepatic lipid deposition. Natural polysaccharides regulate the expression of proteins, such as tight junction proteins, production of small molecule metabolites, and balance of intestinal flora in the intestinal tract to alleviate ALD. Natural polysaccharides also exert therapeutic effects by modulating inflammatory, oxidative, lipid metabolism, and other pathways in the liver. Natural polysaccharides also inhibit alcohol-induced intestinal abnormalities by regulating intestinal flora and feeding back into the liver via the gut-liver axis. However, existing research on natural polysaccharides has many shortcomings: for example, most of the natural polysaccharides for testing are total polysaccharides or crude polysaccharides, progress in research on in vivo metabolic processes and mechanisms is slow, and the degree of industrialisation is insufficient. Finally, we discuss the difficulties in studying natural polysaccharides and future directions to provide a theoretical basis for their development and application.

10.
Front Nutr ; 9: 1121789, 2023.
Article in English | MEDLINE | ID: mdl-36865944

ABSTRACT

Acanthopanax senticosus extract (ASE), a dietary supplement with antifatigue, neuroprotective, and immunomodulatory properties, has been widely used due to its high polyphenol content. Our previous study showed that ASE could be used to treat Parkinson's disease (PD) as it contains multiple monoamine oxidase B inhibitors prescribed in early PD. However, its mechanism remains ambiguous. In this study, we investigated the protective effects of ASE on MPTP-induced PD in mice and explored the underlying mechanisms of action. We found that the administration of ASE significantly improved motor coordination in mice with MPTP-induced PD. As shown by quantitative proteomic analysis, 128 proteins' expression significantly changed in response to ASE administration, most of which were involved with Fcγ receptor-mediated phagocytosis in macrophages and monocytes signaling pathway, PI3K/AKT signaling pathway, and insulin receptor signaling pathway. Furthermore, the network analysis results showed that ASE modulates protein networks involved in regulating cellular assembly, lipid metabolism, and morphogenesis, all of which have implications for treating PD. Overall, ASE served as a potential therapeutic because it regulated multiple targets to improve motor deficits, which could lay the strong foundation for developing anti-PD dietary supplements.

11.
Heliyon ; 9(3): e14609, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36967930

ABSTRACT

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

12.
World J Gastroenterol ; 29(4): 670-681, 2023 Jan 28.
Article in English | MEDLINE | ID: mdl-36742173

ABSTRACT

Colon cancer has attracted much attention due to its annually increasing incidence. Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects. In the past decade, nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention, high accumulation at tumor sites, co-loading with different drugs, and comb-ination of various therapies. This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy, radiotherapy, phototherapy (photothermal therapy and photodynamic therapy), chemodynamic therapy, gas therapy, and immunotherapy. Additionally, the therapeutic mechanisms, limitations, improvements, and future of the above therapies are discussed.


Subject(s)
Colonic Neoplasms , Neoplasms , Photochemotherapy , Humans , Neoplasms/therapy , Nanomedicine , Phototherapy , Drug Delivery Systems , Colonic Neoplasms/drug therapy
13.
Fam Process ; 62(2): 534-556, 2023 06.
Article in English | MEDLINE | ID: mdl-36245316

ABSTRACT

Study of change mechanisms is important to advance theory development and to reveal the active components that make a critical difference in treatment. Improved outcomes in a randomized controlled trial that favored Congruence Couple Therapy (CCT) vs individual-based Treatment-as-Usual (TAU) were correlated within each group. Partial correlations were used to test for mediation effects. The aggregate correlation coefficient of improved variables in addiction and mental health, couple adjustment, emotion regulation (ER) and life stress was moderate for CCT and weak for TAU. CCT showed greater number of mediating effects among improved variables than TAU. The prominence of the process mechanism of improved ER with its mediating effects for addiction and psychiatric symptoms evidenced in both groups is noteworthy, but ER improvement was significantly associated with improved couple adjustment only in CCT. Reduction in life stress in CCT was associated with a broader range of improvements in CCT compared to TAU. Correlation patterns were substantiated by CCT participants' endorsement of treatment targets emphasizing relationship, communication, emotion, problem solving, addiction and intergenerational issues of trauma. TAU participants reported significantly lower endorsements for these treatment targets. The correlation of ER and couple adjustment suggested as a key process mechanism should be further elucidated in future studies to differentiate relationship-based vs individual-based models and their respective outcomes for primary clients and partners. These findings are considered preliminary, requiring larger samples and advanced modelling among variables to provide a more profound mechanism analysis.


Subject(s)
Couples Therapy , Gambling , Humans , Gambling/therapy
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-990858

ABSTRACT

In recent years, treatment of myopia with low-intensity 600-670 nm red light irradiation has attracted extensive attention.A one-year multi-center clinical study in China showed that red light therapy can inhibit axial elongation and the progression of myopia in myopic children.Nevertheless, the underlying mechanism and long-term safety are still to be determined.The longitudinal chromatic aberration theory could explain its effect on retarding myopia in chicks and guinea pigs.However, studies on different species had inconsistent conclusions and even contrary results in primates.The possible mechanisms of its efficacy on myopia control include the temporary increasing choroidal blood flow to mitigate scleral hypoxia, affecting the metabolic signal pathway of cones, stimulating the retina to secrete dopamine through intensive irradiation, affecting circadian rhythm, and stimulating cytochrome C oxidase to reduce oxidative stress to promote cell repair and inhibit apoptosis.In terms of safety, studies revealed the biphasic dose response in red light therapy, that is to say, no adverse event has been reported for low-intensity, low-dose and short-time red light irradiation, but it is necessary to stay alert for photoreceptor cell and retinal pigment epithelium cell damage caused by excessive irradiation.This article reviewed the research progress on the clinical effectiveness, therapeutic mechanism and safety of red light irradiation in the treatment of myopia to provide a theoretical basis for its use in clinical treatment.

15.
Front Microbiol ; 14: 1330029, 2023.
Article in English | MEDLINE | ID: mdl-38268702

ABSTRACT

The global prevalence of Helicobacter pylori (H. pylori) infection remains high, indicating a persistent presence of this pathogenic bacterium capable of infecting humans. This review summarizes the population demographics, transmission routes, as well as conventional and novel therapeutic approaches for H. pylori infection. The prevalence of H. pylori infection exceeds 30% in numerous countries worldwide and can be transmitted through interpersonal and zoonotic routes. Cytotoxin-related gene A (CagA) and vacuolar cytotoxin A (VacA) are the main virulence factors of H. pylori, contributing to its steep global infection rate. Preventative measures should be taken from people's living habits and dietary factors to reduce H. pylori infection. Phytotherapy, probiotics therapies and some emerging therapies have emerged as alternative treatments for H. pylori infection, addressing the issue of elevated antibiotic resistance rates. Plant extracts primarily target urease activity and adhesion activity to treat H. pylori, while probiotics prevent H. pylori infection through both immune and non-immune pathways. In the future, the primary research focus will be on combining multiple treatment methods to effectively eradicate H. pylori infection.

16.
Front Pharmacol ; 13: 1055296, 2022.
Article in English | MEDLINE | ID: mdl-36408255

ABSTRACT

Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.

17.
BMC Complement Med Ther ; 22(1): 281, 2022 Oct 26.
Article in English | MEDLINE | ID: mdl-36289509

ABSTRACT

BACKGROUND: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with Zishen Yutai pills. However, the pharmacological mechanism of action of these pills remains unclear. METHODS: The compounds of Zishen Yutai pills found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of Zishen Yutai pills. The potential targets of compounds were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and Swiss Target Prediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, Therapeutic Target Database, and Genetic Association Database. The overlapping genes between the potential targets of Zishen Yutai pills' compounds and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis. RESULTS: Nineteen compounds in Zishen Yutai pills were detected in the serum of POF mice after oral administration. A total of 695 Zishen Yutai (ZSYT) pill-related targets were screened, and 344 POF-related targets were collected. From the results of Zishen Yutai (ZSYT) pill-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with Zishen Yutai pills. Moreover, the pathway enrichment results suggested that Zishen Yutai pills treated POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis. CONCLUSIONS: Via virtual screening, we found that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis was the potential therapeutic mechanism of Zishen Yutai pills in treating POF. Our study suggested that combining the analysis of Zishen Yutai pills' compounds in blood in vivo in the POF model and network pharmacology prediction might offer a tool to characterize the mechanism of Zishen Yutai pills in the POF.


Subject(s)
Primary Ovarian Insufficiency , Humans , Female , Mice , Animals , Chromatography, High Pressure Liquid , Primary Ovarian Insufficiency/drug therapy , Ligands , Network Pharmacology , Hormones , Membrane Proteins , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
18.
Front Aging Neurosci ; 14: 924262, 2022.
Article in English | MEDLINE | ID: mdl-36062152

ABSTRACT

Brain injury poses a heavy disease burden in the world, resulting in chronic deficits. Therapies for brain injuries have been focused on pharmacologic, small molecule, endocrine and cell-based therapies. Endogenous neural stem cells (eNSCs) are a group of stem cells which can be activated in vivo by damage, neurotrophic factors, physical factor stimulation, and physical exercise. The activated eNSCs can proliferate, migrate and differentiate into neuron, oligodendrocyte and astrocyte, and play an important role in brain injury repair and neural plasticity. The roles of eNSCs in the repair of brain injury include but are not limited to ameliorating cognitive function, improving learning and memory function, and promoting functional gait behaviors. The activation and mobilization of eNSCs is important to the repair of injured brain. In this review we describe the current knowledge of the common character of brain injury, the roles and mechanism of eNSCs in brain injury. And then we discuss the current mobilization strategy of eNSCs following brain injury. We hope that a comprehensive awareness of the roles and mobilization strategy of eNSCs in the repair of cerebral ischemia may help to find some new therapeutic targets and strategy for treatment of stroke.

19.
Front Behav Neurosci ; 16: 995614, 2022.
Article in English | MEDLINE | ID: mdl-36062260

ABSTRACT

Dysphagia is one of the most common manifestations of stroke, which can affect as many as 50-81% of acute stroke patients. Despite the development of diverse treatment approaches, the precise mechanisms underlying therapeutic efficacy remain controversial. Earlier studies have revealed that the onset of dysphagia is associated with neurological damage. Neuroplasticity-based transcranial magnetic stimulation (TMS), a recently introduced technique, is widely used in the treatment of post-stroke dysphagia (PSD) by increasing changes in neurological pathways through synaptogenesis, reorganization, network strengthening, and inhibition. The main objective of this review is to discuss the effectiveness, mechanisms, potential limitations, and prospects of TMS for clinical application in PSD rehabilitation, with a view to provide a reference for future research and clinical practice.

20.
Front Med (Lausanne) ; 9: 891230, 2022.
Article in English | MEDLINE | ID: mdl-35911404

ABSTRACT

We explored the mechanisms and molecular targets of Ejiao Siwu Decoction (EJSW) for treating primary immune thrombocytopenia (ITP) using network pharmacology and molecular docking. Active compounds of EJSW were identified by high-performance liquid chromatography-diode array detector (HPLC-DAD) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) and their targets were obtained from HERB and SwissTargetPrediction, and ITP targets were obtained from Comparative Toxicogenomics Database (CTD) and GeneCards. STRING and Cytoscape were used for protein-protein interaction (PPI) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses by WebGestalt yielded a gene-pathway network, Autodock molecular docking was applied to screen targets and active compounds, and cytokines were detected using a cytometric bead array (CBA) human inflammation kit. We identified 14 compounds and 129 targets, and 1,726 ITP targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumour necrosis factor (TNF), interleukin-6 (IL6), caspase-3 (CASP3) and tumour suppressor protein (TP53) were core targets (nodes and edges). Functional annotation identified cofactor binding and coenzyme binding, and 20 significantly enriched pathways. Active compounds of EJSW were successfully docked with ITP targets. Tumour necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) were upregulated in ITP patients, vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor D (VEGF-D) were downregulated, and EJSW treatment reversed these trends. EJSW may regulate key ITP targets based on the in silico analyses, and protect vascular integrity through AGE-RAGE signalling, complement and coagulation cascades, and VEGF signalling by downregulating TNF-α, IL-1ß and other inflammatory factors.

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