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The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.
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Antidepresivos , Medicamentos Herbarios Chinos , Hipocampo , Plasticidad Neuronal , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Plasticidad Neuronal/efectos de los fármacos , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Animales , Depresión/tratamiento farmacológico , Depresión/fisiopatología , Medicina Tradicional ChinaRESUMEN
BACKGROUND: Xiaoyaosan (XYS), a traditional Chinese medicine formulation, has been used in the treatment of depression. However, no studies have yet identified the active compounds responsible for its antidepressant effects in the brain. STUDY DESIGN: We investigated the antidepressants effects of XYS and identified 18ß-glycyrrhetinic acid (18ß-GA) as the primary compound present in the brain following XYS injection. Furthermore, we explored the molecular mechanisms underlying the antidepressant-like effects of both XYS and 18ß-GA. METHODS: To investigate the antidepressant-like effects of XYS and elucidate the associated molecular mechanisms, we employed various methodologies, including cell cultures, the chronic social defeat stress (CSDS) model, behavioral tests, immunoprecipitation, quantitative PCR (qPCR) assays, Western blotting assays, luciferase assays, chromatin immunoprecipitation (ChIP) assays, immunofluorescence staining, and dendritic spine analysis. RESULTS: We identified 18ß-GA as the primary compound in the brain following XYS injection. In vitro, 18ß-GA was found to bind with ERK (extracellular signal-regulated kinase), subsequently activating ERK kinase activity toward both c-Jun and cAMP response element binding protein (CREB). Moreover, 18ß-GA activated brain-derived neurotrophic factor (BDNF) transcription by stimulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2), c-Jun, and CREB, while also inhibiting methyl CpG binding protein 2 (MeCP2) both in vitro and in vivo. Chronic intraperitoneal (i.p.) administration of 18ß-GA exhibited prophylactic antidepressant-like effects in a CSDS model, primarily by activating BDNF transcription in the medial prefrontal cortex (mPFC). Interestingly, a single i.p. injection of 18ß-GA produced rapid and sustained antidepressant-like effects in CSDS-susceptible mice by engaging the BDNF-tropomyosin receptor kinase B (TrkB) signaling pathway in the mPFC. CONCLUSION: These findings suggest that the activation of BDNF transcription in the mPFC underlies the antidepressant-like effects of 18ß-GA, a key component of XYS in the brain.
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Antidepresivos , Factor Neurotrófico Derivado del Encéfalo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ácido Glicirretínico , Ratones Endogámicos C57BL , Derrota Social , Estrés Psicológico , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ácido Glicirretínico/farmacología , Ácido Glicirretínico/análogos & derivados , Antidepresivos/farmacología , Masculino , Medicamentos Herbarios Chinos/farmacología , Ratones , Estrés Psicológico/tratamiento farmacológico , Depresión/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Receptor trkB/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismoRESUMEN
The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 µg/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0 ± 3.0%, and 48.0 ± 2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.
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Babesia microti , Babesiosis , Gastrópodos , Humanos , Animales , Ratones , Antígenos de Superficie , Grupos Control , Recuento de EritrocitosRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can cause joint inflammation and damage. Leonurine (LE) is an alkaloid found in Leonurus heterophyllus. It has anti-inflammatory effects. HYPOTHESIS/PURPOSE: The molecular mechanisms by which LE acts in RA are unclear and further investigation is required. METHODS: Mice with collagen-induced arthritis (CIA), and RA-fibroblast-like synoviocytes (FLSs) isolated from them were used as in vivo and in vitro models of RA, respectively. The therapeutic effects of LE on CIA-induced joint injury were investigated by micro-computed tomography, and staining with hematoxylin and eosin and Safranin-O/Fast Green. Cell Counting Kit-8, a Transwell® chamber, enzyme-linked immunosorbent assays, RT-qPCR, and western blotting were used to investigate the effects of LE on RA-FLS viability, migratory capacity, inflammation, microRNA-21 (miR-21) levels, the Hippo signaling pathway, and the effects and intrinsic mechanisms of related proteins. Dual luciferase was used to investigate the binding of miR-21 to YOD1 deubiquitinase (YOD1) and yes-associated protein (YAP). Immunofluorescence was used to investigate the localization of YAP within the nucleus and cytoplasm. RESULTS: Treatment with LE significantly inhibited joint swelling, bone damage, synovial inflammation, and proteoglycan loss in the CIA mice. It also reduced the proliferation, cell colonization, migration/invasion, and inflammation levels of RA-FLSs, and promoted miR-21 expression in vitro. The effects of LE on RA-FLSs were enhanced by an miR-21 mimic and reversed by an miR-21 inhibitor. The dual luciferase investigation confirmed that both YOD1 and YAP are direct targets of miR-21. Treatment with LE activated the Hippo signaling pathway, and promoted the downregulation and dephosphorylation of MST1 and LATS1 in RA, while inhibiting the activation of YOD1 and YAP. Regulation of the therapeutic effects of LE by miR-21 was counteracted by YOD1 overexpression, which caused the phosphorylation of YAP and prevented its nuclear ectopic position, thereby reducing LE effect on pro-proliferation-inhibiting apoptosis target genes. CONCLUSION: LE regulates the Hippo signaling pathway through the miR-21/YOD1/YAP axis to reduce joint inflammation and bone destruction in CIA mice, thereby inhibiting the growth and inflammation of RA-FLSs. LE has potential for the treatment of RA.
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Artritis Experimental , Artritis Reumatoide , Ácido Gálico/análogos & derivados , MicroARNs , Animales , Ratones , Vía de Señalización Hippo , Microtomografía por Rayos X , Artritis Reumatoide/metabolismo , Artritis Experimental/inducido químicamente , MicroARNs/genética , Inflamación/metabolismo , Luciferasas/metabolismo , Luciferasas/farmacología , Luciferasas/uso terapéutico , Proliferación Celular , Fibroblastos , Células CultivadasRESUMEN
SCOPE: A growing body of evidence suggests that the harmful gut microbiota in depression patients can play a role in the progression of depression. There is limited research on troxerutin's impact on the central nervous system (CNS), especially in depression. The study finds that troxerutin effectively alleviates depression and anxiety-like behavior in mice by increasing the abundance of beneficial bacteria like Lactobacillus and Firmicutes while decreasing the abundance of harmful bacteria like Proteobacteria, Bacteroides, and Actinobacteria in the gut. Furthermore, the research reveals that troxerutin regulates various metabolic pathways in mice, including nucleotide metabolism, caffeine metabolism, purine metabolism, arginine biosynthesis, histidine metabolism, 2-oxocarboxylic acid metabolism, biosynthesis of amino acids, glycine, serine and threonine metabolism, and Arginine and proline metabolism. CONCLUSIONS: In conclusion, the study provides compelling evidence for the antidepressant efficacy of troxerutin. Through the investigation of the role of intestinal microorganisms and metabolites, the study identifies these factors as key players in troxerutin's ability to prevent depression. Troxerutin achieves its neuroprotective effects and effectively prevents depression and anxiety by modulating the abundance of gut microbiota, including Proteobacteria, Bacteroides, and Actinobacteria, as well as regulating metabolites such as creatine.
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Actinobacteria , Microbioma Gastrointestinal , Hidroxietilrutósido/análogos & derivados , Humanos , Ratones , Animales , Depresión/tratamiento farmacológico , Bacterias , Proteobacteria , ArgininaRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is a significant global health concern that can lead to depression in affected patients. Liquiritin apioside (LA) possesses anti-oxidative and anti-inflammatory properties. However, its anti-inflammatory mechanism in IBD has not been extensively studied. PURPOSE: This study elucidates the pivotal role of LA in alleviating inflammation by regulating gut metabiota-derived metabolites and evaluating its regulative effects on promoting a balance of Th17/Treg cells in colitis mice. METHODS: To evaluate the effect of LA on IBD,16S rRNA gene sequencing and UPLC-QTOF-MS analysis were used to identify the changes of intestinal bacteria and their metabolites. Cytokines levels were determined by ELISA and qPCR, while immune cell ratios were evaluated via flow cytometry. RESULTS: Our findings revealed that LA treatment ameliorated general states of DSS-induced colitis mice and their accompanying depressive behaviors. Moreover, LA restricted the expression of pro-inflammatory cytokines and revised the imbalanced Treg/Th17 differentiation, while promoting SCFAs production in inflamed colon tissues. Fecal microbiota transplantation from LA-fed mice also corrected the imbalanced Treg/Th17 differentiation, indicating that LA-mediated restoration of the colonic Treg/Th17 balance mainly depends on the changes in gut metabolites. CONCLUSION: These results provide scientific evidence explaining the apparent paradox of low bioavailability and high bioactivity in polyphenols, and suggesting that LA could be used as a potential dietary supplement for the prevention and improvement of IBD.
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Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Animales , Ratones , Depresión/tratamiento farmacológico , ARN Ribosómico 16S , Linfocitos T Reguladores , Colitis/tratamiento farmacológico , Inflamación , CitocinasRESUMEN
RATIONALE: 18ß-glycyrrhetinic acid (18ß-GA) has been reported to have anti-inflammatory and neuroprotective effects. However, the therapeutic effect of 18ß-GA in Parkinson's disease (PD) has not been defined. OBJECTIVE: The current study aimed to evaluate the potential therapeutic effects of 18ß-GA in treating PD by mitigating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. RESULTS: The study showed that 18ß-GA has anti-inflammatory effects by upregulating TREM2 expression in BV2 cells, which correlates with the presence of NF-E2-related factor-2 (Nrf2). 18ß-GA reduced inflammation in BV2 cells treated with 1-methyl-4- phenylpyridinium (MPP+) by enhancing TREM2 expression, which promotes an anti-inflammatory microglial phenotype. Repeated administration of 18ß-GA in MPTP-treated mice led to therapeutic effects by enhancing TREM2 expression, resulting in the activation of anti-inflammatory microglia. Moreover, 18ß-GA attenuated the decrease in brain-derived neurotrophic factor (BDNF) levels in both MPP+-induced BV2 cells and MPTP-intoxicated mice, indicating the involvement of BDNF in the beneficial effects of 18ß-GA. CONCLUSIONS: It is probable that activating microglial anti-inflammatory response through TREM2 expression might serve as a novel therapeutic strategy for PD. Additionally, 18ß-GA seems to hold potential as a new therapeutic agent for PD.
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Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratones , Animales , Microglía/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Antiinflamatorios/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Fenotipo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: Neuroinflammation caused by traumatic brain injury (TBI) can lead to neurological deficits. Acupuncture can inhibit neuroinflammation and promote nerve repair; however, the specific mechanism is still unclear. The purpose of this study was to explore whether acupuncture could modulate the M1 and M2 phenotypic polarization of microglia in a rat model of TBI via the toll-like receptor 4 (TLR4)/intracellular toll-interleukin-1 receptor (TIR) domain-containing adaptor inducing interferon-ß (TRIF)/myeloid differentiation factor 88 (MyD88) pathway. METHODS: A total of 90 adult male Sprague-Dawley (SD) rats, SPF grade, were randomly divided into a normal group, model group and acupuncture group. Each group was further divided into three subgroups (first, third, and fifth day groups) according to the treatment time (n = 10 rats/subgroup). We used the modified neurological severity score (mNSS) method to quantify neurological deficits before and after modeling. We used Nissl staining to observe the pathological changes in brain tissue, flow cytometry to detect the proportion of M1 and M2 polarized microglia in the injured area on the first, third and fifth day, and co-immunoprecipitation (Co-IP) to examine TLR4/TRIF/MyD88 expression in microglia on the first, third and fifth day, as well as expression of the amount of binding of TLR4 with TRIF and MyD88. RESULTS: Compared to the model group, mNSS in the acupuncture group gradually decreased and pathological morphology improved. The proportion of CD11b/CD86 positive cells was decreased, while that of CD11b/CD206 was increased in the acupuncture group. Expression of IP TLR4, IP TRIF and IP MyD88 also decreased in the acupuncture group. CONCLUSION: The results of this study demonstrate that one of the mechanisms through which acupuncture mitigates neuroinflammation and promotes nerve repair in TBI rats may be inhibition of M1 phenotypic polarization and promotion of M2 phenotypic polarization through inhibition of the TLR4/TRIF/MyD88 signaling pathway.
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Terapia por Acupuntura , Lesiones Traumáticas del Encéfalo , Ratas , Animales , Masculino , Microglía , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/farmacología , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Ratas Sprague-Dawley , Enfermedades Neuroinflamatorias , Lesiones Traumáticas del Encéfalo/genética , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/farmacologíaRESUMEN
Postmenopausal osteoporosis is a significant threat to human health globally. Genistein, a soy-derived isoflavone, is regarded as a promising anti-osteoporosis drug with the effects of promoting osteoblastogenesis and suppressing osteoclastogenesis. However, its oral bioavailability (6.8%) is limited by water solubility, intestinal permeability, and biotransformation. Fortunately, 8-prenelylated genistein (8PG), a derivative of genistein found in Erythrina Variegate, presented excellent predicted oral bioavailability (51.64%) with an improved osteoblastogenesis effect, although its effects on osteoclastogenesis and intestinal biotransformation were still unclear. In this study, an in vitro microbial transformation platform and UPLC-QTOF/MS analysis method were developed to explore the functional metabolites of 8PG. RANKL-induced RAW264.7 cells were utilized to evaluate the effects of 8PG on osteoclastogenesis. Our results showed that genistein was transformed into dihydrogenistein and 5-hydroxy equol, while 8PG metabolites were undetectable under the same conditions. The 8PG (10-6 M) was more potent in inhibiting osteoclastogenesis than genistein (10-5 M) and it down-regulated NFATC1, cSRC, MMP-9 and Cathepsin K. It was concluded that 8-prenyl plays an important role in influencing the osteoclast activity and intestinal biotransformation of 8PG, which provides evidence supporting the further development of 8PG as a good anti-osteoporosis agent.
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Microbioma Gastrointestinal , Osteoporosis , Humanos , Genisteína/farmacología , Genisteína/metabolismo , Osteoclastos , Intestinos , Osteoporosis/tratamiento farmacológicoRESUMEN
OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.
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Antidepresivos , Medicamentos Herbarios Chinos , Proteínas Quinasas Activadas por AMP/metabolismo , Acetil-CoA Carboxilasa/metabolismo , Adiponectina/metabolismo , Animales , Antidepresivos/farmacología , China , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Glucosa , Hipotálamo/metabolismo , Ratones , Receptores de Adiponectina/metabolismoRESUMEN
Many studies have proven that autophagy plays a pivotal role in the development of depression and it also affects the expression of GLUT4 in the hypothalamus. Xiaoyaosan has been shown to exert antidepressant effects in a variety of ways, but its underlying mechanism by which Xiaoyaosan regulates autophagy as well as GLUT4 in the hypothalamus remains unclear. Thus, in this study, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and set up autophagy blockade as a control to explore whether Xiaoyaosan exerts antidepressant effect by affecting autophagy. We examined the effects of Xiaoyaosan on behaviors exhibited during the open field test, tail suspension test and sucrose preference test, and the changes in autophagy in hypothalamic neurons as well as changes in GLUT4 and the related indicators of glucose metabolism in CUMS-induced depressive mouse model. We found that CUMS- and 3-MA-induced mice exhibited depressive-like behavioral changes, with decreased LC3 expression and increased p62 expression, suggesting decreased levels of autophagy in the mouse hypothalamus. The expression of GLUT4 was also decreased, and it was closely related to the level of autophagy through Rab8 and Rab10. Nevertheless, after the intervention of Xiaoyaosan, the above changes were effectively reversed. These results show that Xiaoyaosan can regulate the autophagy in hypothalamic neurons and the expression of GLUT4 in depressed mice.
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BACKGROUND: Many studies about depression have focused on the dysfunctional synaptic signaling in the hippocampus that drives the pathophysiology of depression. Radix Bupleuri has been used in China for over 2000 years to regulate liver-qi. Extracted from Radix Bupleuri, Saikosaponin D (SSD) is a pharmacologically active substance that has antidepressant effects. However, its underlying mechanism remains unknown. MATERIALS AND METHODS: A chronic unpredictable mild stress (CUMS) paradigm was used as a rat model of depression. SD rats were randomly assigned to a normal control (NC) group or one exposed to a CUMS paradigm. Of the latter group, rats were assigned to four subgroups: no treatment (CUMS), fluoxetine-treated (FLU), high-dose and low-dose SSD-treated (SSDH and SSDL). SSD was orally administrated of 1.50 mg/kg and 0.75 mg/kg/days for three weeks in the SSDH and SSDL groups, respectively. Fluoxetine was administrated at a dose of 2.0 mg/kg/days. SSD's antidepressant effects were assessed using the open field test, forced swim test, and sucrose preference test. Glutamate levels were quantified by ELISA. Western blot and immunochemical analyses were conducted to quantify proteins in the Homer protein homolog 1 (Homer1)-metabotropic glutamate receptor 5 (mGluR5) and mammalian target of rapamycin (mTOR) pathways in the hippocampal CA1 region. To measure related gene expression, RT-qPCR was employed. RESULTS: CUMS-exposed rats treated with SSD exhibited increases in food intake, body weight, and improvements in the time spent in the central are and total distance traveled in the OFT, and less pronounced pleasure-deprivation behaviors. SSD also decreased glutamate levels in CA1. In CA1 region of CUMS-exposed rats, SSD treatment increased mGluR5 expression while decreasing Homer1 expression. SSD also increased expressions of postsynaptic density protein 95 (PSD95) and synapsin I (SYP), and the ratios of p-mTOR/mTOR, p-p70S6k/p70S6k, and p-4E-BP1/4E-BP1 in the CA1 region in CUMS-exposed rats. CONCLUSIONS: SSD treatment reduces glutamate levels in the CA1 region and promotes the expression of the synaptic proteins PSD-95 and SYP via the regulation of the Homer1-mGluR5 and downstream mTOR signaling pathways. These findings suggest that SSD could act as a natural neuroprotective agent in the prevention of depression.
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Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.
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BACKGROUND: Chronic non-specific low back pain (CNLBP) is a common complaint about medical care and carries a heavy social burden. The efficacy of Tuina (TN) or physiotherapy (PT) for CNLBP has been evaluated in previous systematic reviews. However, there is no high-quality evidence to support the efficacy of Tuina. Therefore, this study aims to conduct a large-scale, multicenter, high-quality clinical trial to provide evidence for Tuina to treat CNLBP. METHODS: This is a multicenter, assessor-, and analyst-blinded, randomized controlled trial with 3 parallel arms: TN, PT, and TN combined with PT (Tuina combined with physiotherapy) group. Six hundred twelve eligible CNLBP patients will be randomly assigned to the groups in a 1:1:1 ratio in 3 centers. The TN intervention includes 9-step routine techniques, while the PT intervention includes a physiotherapy treatment plan based on a patient's symptoms. The interventions for both groups will last for 30âminutes and will be carried out for 6 sessions in 8âweeks. The primary outcome will be the visual analog scale pain score. And the secondary outcomes will include the Oswestry Disability Index, spinal range of motion, 36-item short-form health survey. Safety evaluation will be recorded during the whole study. All data in this randomized controlled trial will be analyzed by SAS 9.4. DISCUSSION: The results of this trial will provide evidence to evaluate the efficacy of Tuina's value as a treatment for CNLBP. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000040288, November 27, 2020).
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Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Estudios Multicéntricos como Asunto , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
Abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer, and aberrant m6A regulators have been identified as novel anticancer drug targets. Both traditional medicine-related approaches and modern drug discovery platforms have been used in an attempt to develop m6A-targeted drugs. Here, we provide an update of the latest findings on m6A modification and the critical roles of m6A modification in cancer progression, and we summarize rational sources for the discovery of m6A-targeted anticancer agents from traditional medicines and computer-based chemosynthetic compounds. This review highlights the potential agents targeting m6A modification for cancer treatment and proposes the advantage of artificial intelligence (AI) in the discovery of m6A-targeting anticancer drugs. Three stages of m6A-targeting anticancer drug discovery: traditional medicine-based natural products, modern chemical modification or synthesis, and artificial intelligence (AI)-assisted approaches for the future.
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Inteligencia Artificial , Neoplasias , Adenosina/química , Descubrimiento de Drogas , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , PronósticoRESUMEN
BACKGROUND: Depression is one of the most frequent and severe psychiatric conditions. Many chemical drugs to treat depression are associated with adverse reactions and have shortcomings. Traditional Chinese medicine is of great significance in the prevention and treatment of depression. Xiaoyao pills has achieved good results in clinical application, which has the advantages of quick effect and no obvious adverse reactions. The aim of our study is to evaluate the efficacy and safety of Xiaoyao pills on mild to moderate depression patients. METHODS: This study is a multi-centre, double-blinded, randomized and placebo-controlled clinical trial. A total of 108 participants are assigned to three groups: Xiaoyao pill group taking Xiaoyao pills twice daily for 4 weeks, placebo group taking placebos twice daily for 4 weeks and normal group without taking any drug. The primary and secondary outcome measures are the Hamilton Depression Scale (HAMD) and Traditional Chinese Medicine (TCM) Syndrome Scale. The assessment is at baseline (before treatment initiation), 1 week, 2 weeks 4 weeks after the first treatment. Exploratory outcome is also assessed to explore the mechanism of Xiaoyao pills at baseline and 4 weeks. DISCUSSION: The results from this study will provide clinical evidence on the efficacy and safety of Xiaoyao pills in patients with mild to moderate depression with syndrome of liver stagnation and spleen deficiency. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN12746343. Registered on September 25, 2020.
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Depresión , Medicamentos Herbarios Chinos , Depresión/diagnóstico , Depresión/tratamiento farmacológico , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Medicina Tradicional China , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Depression is the second most common psychiatric disorder, affecting more than 340 million people of all ages worldwide. However, the mechanisms underlying the development of depression remain unclear, and existing antidepressants may cause clinical dependence and toxic side effects. Recently, emerging evidence from the fields of neuroscience, genetics, and genomics supports the modulatory role of long non-coding RNA (lncRNA) in depression. LncRNAs may mediate the pathogenesis of depression through multiple pathways, including regulating neurotransmitters and neurotrophic factors, affecting synaptic conduction, and regulating the ventriculo-olfactory neurogenic system. In addition, relying on genome-wide association study and molecular biological experiment, the possibility of lncRNA as a potential biomarker for the differential diagnosis of depression and other mental illnesses, including schizophrenia and anxiety disorders, is gradually being revealed. Thus, it is important to explore whether lncRNAs are potential therapeutic targets and diagnostic biomarkers for depression. Here, we summarize the genesis and function of lncRNAs and discuss the aberrant expression and functional roles of lncRNAs in the development, diagnosis, and therapy of depression, as well as the deficiencies and limitations of these studies. Moreover, we established a lncRNA-miRNA-mRNA-pathway-drug network of depression through bioinformatics analysis methods to deepen our understanding of the relationship between lncRNA and depression, promoting the clinical application of epigenetic research.
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Depresión , ARN Largo no Codificante/genética , Biología Computacional , Depresión/genética , Depresión/fisiopatología , Epigenómica , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Estudio de Asociación del Genoma Completo , Humanos , MicroARNs/genética , ARN Mensajero/genéticaRESUMEN
Introduction: Babesia microti (B. microti) is the dominant species responsible for human babesiosis, which is associated with severe hemolytic anemia and splenomegaly because it infects mammalian erythrocytes. The actual prevalence of B. microti is thought to have been substantially underestimated. Methods: In this study, Bagg's albino/c (BALB/c) mice were intraperitoneally injected with B. microti-infected erythrocytes, and parasitemia was subsequently measured by calculating the proportion of infected erythrocytes. The ultrastructure of infected erythrocytes was observed using scanning and transmission electron microscopes. Quantifying phosphatidylserine (PS) exposure, oxidative stress, intracellular Ca2+, and erythropoiesis of erythrocytes were done using flow cytometry. The physiological indicators were analyzed using a Mindray BC-5000 Vet automatic hematology analyzer. Results: Of note, 40.7 ± 5.9% of erythrocytes changed their structure and shrunk in the B. microti-infected group. The percentage of annexin V-positive erythrocytes and the levels of reactive oxygen species (ROS) in the erythrocytes were higher in the B. microti-infected group than in the control group at 10 dpi. Significant splenomegaly and severe anemia were also observed following B. microti infection. The parasitemia level in the B. microti-infected splenectomized group was higher than that of the B. microti-infected sham group. The population of early erythroblasts increased, and the late erythroblasts decreased in both the bone marrow and spleen tissues of the B. microti-infected group at 10 dpi. Discussion: PS exposure and elevated ROS activities were hallmarks of eryptosis in the B. microti-infected group. This study revealed for the first time that B. microti could also induce eryptosis. At the higher parasitemia phase, the occurrence of severe anemia and significant changes in the abundance of erythroblasts in B. microti-infected mice group were established. The spleen plays a critical protective role in controlling B. microti infection and preventing anemia. B. microti infection could cause a massive loss of late erythroblasts and induce erythropoiesis.