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Gancao Fuzitang originates from the Treatise on Febrile Diseases and Miscellaneous Diseases （《伤寒杂病论》） and is mainly used to treat pain in the bones and joints and symptoms such as no flexion or extension. It has the effect of tonifying the spleen and kidney and removing dampness and turbidity， so it is widely used in the clinical treatment of various bone and joint diseases. This article reviewed the clinical research and mechanism of Gancao Fuzitang in the treatment of bone and joint diseases. The research has found that this prescription has good efficacy in treating bone and joint diseases such as rheumatoid arthritis， rheumatoid arthritis， ankylosing spondylitis， gout， and intervertebral disc herniation. Its mechanism of action may be related to regulating the level of inflammatory factors， antioxidation， and the protein expression of inflammatory and apoptotic cell-related pathways， improving bone and joint diseases， and alleviating related symptoms. This study can provide a reference for further deepening the research on the prevention and treatment of bone and joint diseases with Gancao Fuzitang.
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Ulcerative colitis （UC） is a chronic inflammatory bowel disease with complex etiology. The pathogenesis of this disease， due to a combination of factors， is complex and has not yet been elucidated. Among them， intestinal mucosal barrier damage is the basic pathological change of UC. As a non-destructive response of cells， autophagy regulates intestinal mucosal immunity， inflammation， oxidative stress， and bacterial homeostasis through degradation and reabsorption to actively repair damaged intestinal mucosal barrier， exerting a key role in the occurrence and development of UC. The disease is mainly treated clinically with aminosalicylic acid preparations， glucocorticoids， and immunosuppressants. Western medicine treatment of the disease has a fast onset of effect， and the short-term efficacy is definite， but the long-term application is easy to be accompanied by more adverse reactions. Moreover， some drugs are expensive， bringing great physical and mental pain and economic burden to patients. Therefore， it is urgent to explore new therapies with stable efficacy and mild adverse effects. In recent years， a large number of studies have shown that Chinese medicine can regulate autophagy of the intestinal mucosa with multiple targets and effects and repair the intestinal mucosal barrier function， thereby inhibiting the development of UC. Many experiments have shown that the active ingredient or monomers and compound formulas of Chinese medicine can improve the immunity of the intestinal mucosa， inflammation， oxidative stress， and flora by regulating the level of autophagy to maintain the normal function of the intestinal mucosal barrier to effectively intervene in UC， providing a new measure for the prevention and treatment of UC. However， there is a lack of systematic review of Chinese medicine in regulating the level of autophagy in the intestinal mucosa for the prevention and treatment of UC. Therefore， based on the current research on UC， autophagy process， and Chinese medicine treatment， this article reviewed the relationship of autophagy and its key target proteins with UC to clarify the key role of autophagy in UC production and systematically summarized Chinese medicines targeting the regulation of autophagy to treat UC in recent years to provide new ideas for the treatment and drug development of UC.
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Abstract Immunotherapy is one of the most innovative treatments in the current field of oncology and consists of stimulating the immune system to eliminate tumoral cells. Monoclonal antibodies (mAbs) are glycoproteins secreted by B-cells capable of recognizing and neutralizing foreign organisms or antigens. Structurally, they are composed of two heavy and two light chains. The generation of therapeutic mAbs is one of the most developed and fastest-growing areas of the biotechnological and pharmaceutical industries and is an important adjunct to cancer therapy. Several antibodies have been approved for human administration and can be mouse-derived, chimeric, humanized, or fully human. mAbs main mechanism of action includes the lysis of the tumoral cells through inducing apoptosis, phagocytosis, complement activation, or signaling inhibition.
Resumen La inmunoterapia es un tratamiento innovador para la oncología actual, que consiste en la estimulación del sistema inmunitario para la eliminación de las células tumorales. Los anticuerpos monoclonales (mAbs) son glicoproteínas secretadas por los linfocitos B, capaces de reconocer y neutralizar organismos extraños o antígenos. Estructuralmente se componen de dos cadenas pesadas y dos cadenas ligeras. La generación de mAbs terapéuticos es una de las áreas de mayor crecimiento en la industria biotecnológica y farmacéutica y representa un complemento importante en la terapia del cáncer. Existen diversos mAbs que han sido aprobados para su administración en humanos, y pueden ser derivados de ratón, quiméricos, humanizados o completamente humanos. Los mecanismos de acción consisten principalmente en la lisis de las células tumorales a través de la inducción de la apoptosis, fagocitosis, activación del complemento o inhibición de la señalización celular.
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Similia Similibus Curantur is also called the law of similars. That is, when a drug produces pathological/pathogenic symptoms in healthy individual means, the same drug can relieve similar kinds of symptoms in individuals with the disease. The biological, pharmacological and toxicological action of capsaicin alkaloids is a perfect example to explain the Similia Similibus Curantur principle. Most of the drugs in homoeopathic materia medica contain toxicological, pharmacological, drug-proving, and traditional use-related symptoms and indications. Abnormal sensations and symptoms of the disease are caused by the involvement of a specific receptor or molecular pathway and gene functions. These receptors or molecules may be stimulated or suppressed by environmental, natural or artificial agents. In such conditions, the administration of specific homoeopathic medicine having a similar kind of affinity towards the particular receptors or molecules involved in the disease process leads to modulation of such receptor or molecular pathways (e.g., desensitization, sensitization, inhibition). These kinds of actions cause the betterment of symptoms or curative effects. So “Similia similibus curanter” can be understood as a similar receptor or molecular pathway involved in both drug molecules biological/ pharmacological and toxicological action and disease pathogenesis". The selection of medicine is by comparing the similarity between the receptor or molecular pathway in disease pathogenesis and drug pathogenesis. To avoid unwanted aggravations or side effects while using mother tinctures or solutions, administer them less than their physiological dose. The theory of the pharmacological basis of Similia Similia Curantur creates a rational method to apply this Similia Principle. Based on this theory, there is a possibility of discovering Novel drugs in the future that acts and gives a cure in similia similibus curantur way.
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ObjectiveTo analyze the clinical application hotspots， development trends， compatibility characteristics， application rules， and formulation mechanisms of the Chinese marine drug pair Haliotidis Concha-Oystreae Concha in order to provide references for its clinical medication and further research. MethodBy means of various modern literature databases such as China National Knowledge Infrastructure （CNKI）， modern clinical prescriptions containing Haliotidis Concha-Oystreae Concha， as well as the clinical application hotspots， were retrieved， followed by visualized analysis of hotspots and development trends of their clinical applications using Citespace. The drug composition， efficacy and indications， and drug dosages in the prescriptions were statistically analyzed. Additionally， various statistical software including SPSS Modeler 18.0 were employed to analyze the indications， syndromes， and formulation rules of Haliotidis Concha-Oystreae Concha. ResultThe visualized analysis included 90 articles， revealing a gradual decrease in publications in this field in recent years. Key clinical application keywords were identified as hypertension， collateral deficiency producing wind， insomnia， etc. Eighty clinical prescriptions were retrieved， involving 121 drugs. Frequency analysis of compatibility demonstrated that the top 10 drugs were Uncariae Ramulus cum Uncis， Gastrodiae Rhizoma， Os Draconis， Achyranthis Bidentatae Radix， Paeoniae Radix Alba， Chrysanthemi Flos， Scutellariae Radix， Gardeniae Frucuts， Glycyrrhizae Radix et Rhizoma， and Polygoni Multiflori Caulis. Association rule analysis showed that core combinations included "Uncariae Ramulus cum Uncis-Achyranthis Bidentatae Radix" and "Os Draconis-Pheretima-Chuanxiong Rhizoma". Through factor reliability analysis， new drug combinations were derived， such as "Gastrodiae Rhizoma-Polygoni Multiflori Caulis-Eucommiae Cortex-Taxilli Herba-Leonuri Herba"， "Achyranthis Bidentatae Radix-Uncariae Ramulus cum Uncis"， "Scutellariae Radix-Glycyrrhizae Radix et Rhizoma-Margarita-Prunellae Spica"， "Os Draconis-Pheretima-Bombyx Batryticatus"， "Chrysanthemi Flos-Chuanxiong Rhizoma"， "Poria-Acori Tatarinowii Rhizoma"， and "Paeoniae Radix Alba-Gardeniae Fructus-Sclerotium Poriae Pararadicis". The Haliotidis Concha-Oystreae Concha drug pair was mainly used to treat diseases with liver Yang hyperactivity syndrome， with hypertension accounting for 40.00%， migraines for 30.00%， and dizziness for 15.00%. In the treatment of liver Yang hyperactivity syndrome， the main categories of compatible drugs were liver-pacifying and wind-extinguishing ones （19.86%）， blood-activating and stasis-resolving ones （12.13%）， and spirit-calming ones （10.08%）. High-frequency drugs in the prescriptions function to reduce blood pressure through multiple pathways， such as increasing nitric oxide （NO） levels， downregulating angiotensin Ⅱ （Ang Ⅱ）， and inhibiting angiotensin-converting enzyme （ACE）. ConclusionThrough comprehensive analysis of the results， the Haliotidis Concha-Oystreae Concha drug pair is commonly used for hypertension with liver Yang hyperactivity syndrome， and is often combined with deficiency-tonifying， liver-pacifying and wind-extinguishing， heat-clearing， and spirit-calming drugs， aiming to simultaneously extinguish wind， relieve spasms， and pacify the liver to subdue Yang， while also clearing heat to relax bowels， stabilizing the mind， and enhancing the liver-pacifying and Yang-subduing effects of this drug pair.
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Objective To explore the possible mechanism of Radix Paeoniae Alba on hepatic fibrosis based on network pharmacology. Methods Tcmsp database was used to screen the active components of Paeonia alba. With the help of PubChem and Swiss target prediction database, the potential action targets of the effective components of Paeonia Alba were predicted. GeneCards and OMIM databases were used to screen the corresponding targets of liver fibrosis, and venn2.1.0 was used to obtain the common targets of white peony and liver fibrosis. Cytoscape 3.9.0 software was used to build the network diagram of “white peony - active ingredients - intersection target - liver fibrosis” and to predict the main active sites. String database was used to draw the PPI network. Go analysis of effective targets and enrichment analysis of KEGG in pathway were performed by David database. Results Six effective components, 213 targets of Paeonia Alba and 155 hepatic fibrosis targets were screened. There were 49 targets of Radix Paeoniae Alba in the treatment of liver fibrosis. The main active ingredients are kaempferol, paeoniflorin, mairin and β-Sitosterol. Go enrichment analysis showed 269 biological processes, 30 cell compositions, 64 molecular functions, and 67 pathways in KEGG pathway enrichment analysis. Conclusion The mechanism of anti-hepatic fibrosis of Radix Paeoniae Alba has been preliminarily studied through network pharmacology, which shows that Radix Paeoniae Alba has multi-component, multi-target, and multi-channel effects, and provides reference for further experimental research.
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Alzheimer's disease(AD)is a neurode-generative disease with insidious onset and progressive development.In recent years,the prevalence of AD has shown a linear upward trend.At present,its pathogene-sis is not clear.Lycium barbarum polysaccharide(LBP)is one of the main effective components extracted from the dried ripe fruit of Lycium barbarum L.,a solanaceae plant.It has many pharmacological effects such as anti-aging,anti-oxidation,anti-fibrosis,anti-inflammation,neu-roprotection and immunomodulation.LBP has been widely studied in the field of prevention and treatment of AD because of its good anti-aging and neuroprotective effects.Its prevention and treatment mechanism mainly includes the following points:① Regulating the apoptosis of nerve cells.Studies have shown that the signal pathway com-posed of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)participates in a series of processes such as the growth,proliferation and apoptosis of neurons and plays an important regulatory role.LBP can reduce the number of cell apoptosis,increase the expression levels of autophagy protein Beclin1 and microtubule-associated protein 1 light chain 3Ⅱ(LC3Ⅱ),and decrease the expres-sion levels of p-Akt and phosphorylated mammalian target protein of rapamycin(p-mTOR),which indicates that Lycium barbarum polysaccharide can prevent and treat AD by inhibiting PI3K/Akt/mTOR pathway and improv-ing the autophagy level of cells.②Inhibition of amyloid β-protein(Aβ)production.Aβ is the main component of senile plaque,which is regarded as the main biomarker of AD.It is found that the neurotoxicity of Aβ plays a role by increas-ing the influx of Ca2+ mediated by N-methyl-D-aspartate receptor in the process of signal transduction in the brain,and then generating reactive oxygen species(ROS)and apoptosis signals.LBP can promote autophagy of HT22 cells by inhibiting PI3K/Akt pathway,which has a protec-tive effect on Aβ-induced toxicity.③ Inhibit the produc-tion of inflammatory cytokines.In the pathogenesis of AD,microglia are activated when they feel pathological accumulation of Aβ,and then cell surface immune and adhesion molecules such as cluster of differentiation 45(CD45),CD40,CD36 and integrins are activated,thereby recruiting Src family kinases and activating MAPK path-way,leading to over-expression of proinflammatory fac-tors.A large number of cytokines and chemokines are produced,which may lead to synapse damage and loss.For example tumor necrosis factor-α(TNF-α)can induce neuronal apoptosis and injury.The production of interleu-kin,and other cytokines and chemokines may also lead to microglia activation,astrocyte proliferation,and further secretion of proinflammatory factors and amyloid deposi-tion,thus making the neuroinflammatory cascade perma-nent.LBP can down-regulate the expression of TNF-α and IL-1β genes,reduce the level of intracellular ROS,and improve the learning and memory ability of AD patients.In this paper,the mechanism of Lycium barbarum polysaccharide in preventing and treating AD is reviewed,in order to provide basis for drug development and clini-cal application.
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【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.
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Compared with other drug-resistant strains, Acinetobacter baumannii has the characteristics of serious drug resistance, high mortality and difficulty to treat. As the phenomena of resistance to existing anti-Acinetobacter baumannii drugs continuously occurs, the development of new anti-Acinetobacter baumannii drugs is urgent. This review introduces the clinical application and research progress of anti-Acinetobacter baumannii drugs, aiming to provide help for the research and development of anti-Acinetobacter baumannii drugs.
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Objective To explore the mechanism of action of curcumin in the treatment of silicosis by network pharmacology combined with molecular docking technology. Methods The targets prediction network of curcumin in treating silicosis was established based on the collection of targets of curcumin and silicosis in multiple databases, cross-targets were submitted to the STRING database, and their connectivity was analyzed by Cytoscape software. Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the top 20 genes. The molecular docking was performed on the key targets to study the mechanism of action of curcumin in treating silicosis. Results A total of 311 targets related to curcumin, 270 targets related to silicosis, and 74 cross-targets were obtained from the databases. GO function analysis revealed 2 665 related pathways, and KEGG pathway enrichment analysis revealed 188 related pathways. Molecular docking results showed that curcumin had good binding ability with the targets of mitogen-activated protein kinase 3 (MAPK3), interleukin (IL) 6, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), signal transducer and activator of transcription 3, albumin, Jun proto-oncogene, tumor necrosis factor (TNF), IL1B, tumor protein p53, C-C motif chemokine ligand 2 and fibronectin 1. Conclusion The therapeutical effects of curcumin on silicosis were implemented through multi-targets and multi-pathways. Curcumin may play a role in the treatment of silicosis by binding to the core targets MAPK3, IL6, AKT1, VEGFA and TNF and regulating the MAPK, IL6, TNF, phosphatidylinositol 3-kinase/protein kinase B and VEGF signaling pathways.
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Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.
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Knee osteoarthritis （KOA） is a common degenerative joint disease in the middle-aged and elderly. The incidence of KOA is rising as the population aging aggravates and the obese population grows. KOA seriously affects the health and daily life of the patients. The commonly used drugs for the symptomatic treatment of KOA include non-steroidal anti-inflammatory drugs， cartilage protective drugs， and opioid analgesics， which have limited therapeutic effects and induce obvious adverse drug reactions. Eucommiae Cortex is one of the commonly used Chinese herbal medicines for the treatment of KOA， while its pharmacological material basis and mechanism remain unclear， which limits its clinical application. The active ingredients of Eucommiae Cortex for treating KOA mainly include iridoids （geniposide， aucubin）， lignans （pinoresinol diglucoside）， flavonoids （quercetin， astragaloside， baicalein， hyperoside， and kaempferol）， phenylpropanoids （chlorogenic acid）， and polysaccharides. These compounds regulate the levels of inflammatory cytokines， inhibit oxidative stress， protect chondrocytes， balance the synthesis and degradation of extracellular matrix， and control the progression of KOA via the mitogen-activated protein kinase， nuclear factor-κB， phosphatidylinositol-3-kinase/protein kinase B， and Janus kinase 1/signal transducer and activator of transcription 3 signaling pathways. This paper introduces the mechanisms of Eucommiae Cortex and its active components in the treatment of KOA， aiming to provide a theoretical basis for the development of new drugs for KOA.
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Osteoporosis （OP） is a systemic metabolic disease that affects the health of middle-aged and elderly people by crosslinking multiple signaling pathways. With the increasing aging of the population， the incidence of OP is also increasing year by year. Because of a series of problems such as high incidence， difficulty in treatment， and poor prognosis， it has been widely studied and reported by scholars in China and abroad. At present， the drugs used by western medicine are mainly divided into two categories： Bone resorption inhibitors and bone formation promoters. Although the efficacy is reliable， there are still deficiencies such as poor dependence of patients on the drug， uncontrollable side effects， and high costs. However， in recent years， with the continuous deepening and innovation of traditional Chinese medicine （TCM） research， the treatment of OP by TCM has been widely recognized in clinical practice. Many scholars have found that the mechanism of TCM in the treatment of OP includes the widespread involvement of mitogen-activated protein kinase （MAPK） signaling pathway， which mainly promotes the differentiation of bone marrow mesenchymal stem cells （BMSCs） to osteoblasts （OB）， inhibits the differentiation of osteoclasts （OC）， and improves the expression of osteogenesis-related factors alkaline phosphatase （ALP）， Runt-associated transcription factor 2 （Runx2）， type Ⅰ collagen （ColⅠ） to treat OP. Although the current research on the TCM treatment of OP through the MAPK pathway is deepening， there are still certain deficiencies in the study of its molecular mechanism. Therefore， this paper reviewed the relationship between the MAPK signaling pathway and key target protein factors and OP to clarify the important role of the MAPK signaling pathway in OP. At the same time， the targeted regulation of MAPK signaling pathways by TCM to treat OP was systematically summarized in order to provide a scientific basis for the further accurate treatment of OP in TCM.
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ObjectiveTo explore the antidepressant effect of Sophora flavescens seed extract and its molecular mechanism. MethodA mouse depression model was established by intraperitoneal injection of lipopolysaccharide（LPS）， and normal group， model group， fluoxetine group（2.5 mg·kg-1）， and S. flavescens seed low， medium and high dose groups（200， 400， 800 mg·kg-1） were set up for 7 d of consecutive gavage. Then the antidepressant effect of S. flavescens seed extract was evaluated by using open field test， elevated plus maze test and forced swimming test. Pathological morphological changes in the hippocampal tissue was observed by hematoxylin-eosin（HE） staining. Protein expression levels of G1/S-specific cyclin D1（Cyclin D1）， Wnt1， β-catenin and phosphorylated glycogen synthase kinase-3β（p-GSK-3β） in mouse brain tissues were detected by Western blot. Hippocampal cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL）. ResultThe results of mouse behavioral experiments showed that compared with the normal group， the speed of movement in the open field and the distance of movement in the central area of the open field， and the time spent on the open arms of the elevated plus maze were significantly reduced in the model group（P<0.01）， while immobility time in the forced swimming test was significantly increased（P<0.05）. Compared with the model group， the S. flavescens seed medium and high dose groups had increased speed of movement in the open field test and time spent on the open arms of the elevated plus maze test（P<0.05， P<0.01）， and decreased immobility time in the forced swimming test（P<0.05）， the distance of movement in the central area of the open field test increased in the high dose group（P<0.05）. HE staining results showed that compared with the normal group， the hippocampal neuron structure of mice in the model group was damaged. Compared with the model group， after treatment of S. flavescens seed extract， the pathological state of the mouse hippocampal neuron structure was alleviated， and the neurons increased， were neatly arranged， and the cytoplasm was clear. Western blot results showed that the protein expression levels of Wnt1 and β-catenin in mouse brain tissue were significantly decreased（P<0.01）， while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly increased（P<0.01） after LPS injection. Compared with the model group， protein expression levels of Wnt1 and β-catenin in brain tissue of S. flavescens seed medium and high dose groups were significantly increased（P<0.01）， while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly decreased（P<0.01）. TUNEL staining results showed that the hippocampal cell apoptosis rate in the model group was significantly increased compared with that of the normal group（P<0.01）， while the hippocampal cell apoptosis rate in the S. flavescens seed medium and high dose groups was significantly decreased compared with that of the model group（P<0.01）. ConclusionS. flavescens seed extract can effectively improve the severity of depression in LPS-induced depressed mice， and its molecular mechanism is related to the regulation of neuroinflammation and hippocampal neuronal apoptosis mediated by Wnt/β-catenin signaling pathway.
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Objective To investigate the inhibitory effect of cryptotanshinone (CPT) on human breast cancer cell MCF7 and its mechanism. Methods The survival rate of MCF7 cells was measured by MTT assay. Cell apoptosis was detected by Annexin V/PI assay and Hoechst 33258 fluorescence staining assay. Cell cycle and reactive oxygen species were detected by flow cytometry. Cell migration and invasion were detected by cell scratch test and Transwell chamber test. The surface molecules CD44 and CD24 were detected by flow cytometry and microsphere culture. The expression of cell-associated proteins was detected by Western blot. Results CPT inhibited the proliferation of MCF7 cells in a dose-dependent manner, and the 24 h IC50 value was 19.24 μmol/L. Compared with the untreated group, the CPT-treated group showed cell cycle arrested in the S phase, and apoptosis was induced. The results of the cell scratch and Transwell chamber tests showed that CPT significantly inhibited the migration and invasion of MCF7 cells. Furthermore, CPT reduced the CD24-/LowCD44+ cell population in MCF7 cell-derived microspheres. Western blot results showed that CPT could up-regulate the expression of Bax protein, down-regulate the expression of BCL-2, PI3K-p85, Akt, N-cadherin, Twist1, Sox2, Oct4, and Nanog protein, effectively inhibit the phosphorylation of ER-α, and decrease the expression of ABCG2. Conclusion CPT can inhibit the proliferation of MCF7 cells by inhibiting the migration and invasion of MCF7 cells, decreasing the number of CD24-/lowCD44+ cells and affecting the expression of tumor stem cell-related proteins.
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Non-small cell lung cancer （NSCLC） is a malignant tumor of the respiratory system with a high incidence. The early symptoms are not typical， and most patients are diagnosed at an advanced stage， which seriously threatens the lives and health of people. Surgery， chemotherapy， and targeted therapy are the main means of treatment at present， but the consequent drug resistance and adverse reactions restrict these treatment methods with certain limitations. In recent years， with the development of traditional Chinese medicine （TCM） in tumor resistance， TCM has attracted extensive attention for its obvious therapeutic effect and fewer adverse reactions. Numerous signaling pathways are involved in the formation and development of NSCLC， where phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway is one of the key regulatory pathways. The PI3K/Akt/mTOR signaling pathway affects the proliferation， invasion， and metastasis of NSCLC cells by affecting the cycle， inhibiting the apoptosis， inhibiting the autophagy of tumor cells， and promoting tumor neovascularization. As revealed by the recent literature， Chinese medicine plays an indispensable role in NSCLC cell autophagy， cell cycle， apoptosis， invasion and metastasis， neovascularization， and reversal of drug resistance by regulating the PI3K/Akt/mTOR signaling pathway. Although some Chinese medicinal extracts or compounds have made great breakthroughs in some mechanisms of action in the treatment of NSCLC， these studies only remain at the level of in vitro cell experiments and animal studies in vivo. Researchers are faced with the great challenge of "transforming the research results of Chinese medicines into clinical applications". Based on the current research status in China and abroad， this paper reviewed Chinese medicine in the intervention in NSCLC through the regulation of PI3K/Akt/mTOR signaling pathway in recent years， in order to open up new ideas for NSCLC drug therapy research and also provide a useful reference for further mechanism research.
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@#The tyrosine kinase activity of epidermal growth factor receptor (EGFR) plays a key role in tumor cell proliferation, invasion, migration, and drug resistance. Studies have shown that non-small cell lung cancer patients with somatic driver gene EGFR mutations are sensitive to and can benefit from EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Nevertheless, EGFR-TKIs-related adverse events should not be ignored. Common adverse events such as diarrhea, acne-like rash and paronychia are usually manageable; although the incidence of interstitial lung disease is low, once it occurs, it is a serious threat to patients' life, and its pathogenesis is still unclear. There is very limited animal experimental and clinical research evidence on the potential mechanism of EGFR-TKIs-related interstitial lung disease in the available literature. Based on this, this article reviews the association between EGFR-TKIs and interstitial lung disease, at the same time, also discusses the research progress of EGFR-TKIs-related interstitial lung disease in combination with cytotoxic drugs or immunotherapeutic drugs and EGFR-TKIs, in order to provide a reference for the prevention and treatment of EGFR-TKIs-related interstitial lung disease in clinical practice in the future.
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Idiopathic pulmonary fibrosis （IPF） is a progressive interstitial lung disease with unknown etiology and poor prognosis. At present， there are few antifibrotic drugs， which have limited efficacy and cause diverse side effects in the treatment of IPF， failing to meet the clinical needs. Therefore， it is urgent to develop more safe and effective drugs to treat IPF. Traditional Chinese medicine （TCM） has garnered increasing attention in recent years in the treatment of IPF due to its unique advantages. Increasing studies have shown that Chinese medicines have remarkable therapeutic effects on IPF and broad application prospects. However， the unclear material basis and mechanism in treating IPF hinders the modernization， internationalization， and clinical application of Chinese medicines. Therefore， it is essential to decipher the mechanism of the active components in Chinese medicines in treating IPF， which has gradually become a hot spot in the research on IPF. Increasing research results have demonstrated that anti-inflammation， anti-oxidation， inhibition of epithelial-mesenchymal transition are involved in the treatment of IPF with these active components， whereas the systematic research and summary remain to be carried out. By reviewing the articles about the treatment of IPF with the active components in Chinese medicines in recent years， this paper summarizes the mechanism and experimental studies and puts forward the existing problems in the research on the mechanism， aiming to provide references for the further basic research on IPF and the development of targerted drugs.
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Obesity type 2 diabetes mellitus （T2DM） strengthens insulin resistance （IR） and metabolic abnormalities and significantly increases the risk of heart disease， cancer， and other diseases， and it is characterized by IR and malnutrition. As a metabolic regulation center， adenosine phosphate activated protein kinase （AMPK） mainly responds to the changes in intracellular serine/threonine kinase adenosine monophosphate （AMP） levels. After its activation， AMPK converts the cell metabolism mode from synthesis to decomposition to improve energy metabolism and acts on pathological conditions such as inflammation， ischemia， obesity， and aging. In recent years， a large number of studies have found that AMPK is an important target for the treatment of obesity T2DM. Traditional Chinese medicine（TCM） monomers/extracts and TCM formulas mainly affect the mammalian target of rapamycin （mTOR）， recombinant sirtuin 1 （SIRT1）， nuclear factor erythroid 2-related factor 2 （Nrf2）， nuclear factor kappa-B （NF-κB）， and other key signaling factors by regulating the AMPK signaling pathway， so as to achieve a variety of effects such as regulating metabolism and autophagy， reducing oxidative stress and inflammatory response， and treating obesity T2DM. It also has advantages such as multiple targets， comprehensiveness， and low toxicity. The regulation of the AMPK pathway by TCM in the prevention and treatment of obesity T2DM has become an important research direction at the present and in the future， but there is no systematic summary and induction in this field. Therefore， this article attempts to summarize the composition and regulatory mechanisms of the AMPK signaling pathway in affecting obesity. It provides a review of the current research status of TCM in regulating the AMPK signaling pathway for the prevention and treatment of obesity T2DM， so as to provide a reference for the diagnosis and treatment of obesity T2DM in TCM and the development of new drugs.
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Pancreatic cancer is one of the most destructive malignant tumors； the pathogenesis of this disease is complex and is closely related to genetic susceptibility， chronic pancreatitis， and gene mutations in signaling pathways. The phosphoinositide 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical cancer signaling pathway that is aberrantly activated in pancreatic cancer cells. In recent years， it has been found that traditional Chinese medicine （TCM） monomers show special activity in the treatment of pancreatic cancer and can be potential drug for the treatment of pancreatic cancer. Based on PI3K/Akt signaling pathway， this paper summarizes the mechanism of TCM monomer intervening in pancreatic cancer and finds that TCM monomer of alkaloids （sinomenine， dictamnine， dauricine， etc.）， terpenoids （saikosaponin A， linderalactone， isoalantolactone， etc.）， phenols （6-gingerol， curcumin， pterostilbene， etc.）， flavonoids （fisetin， kaempferol， quercetin， etc.） and quinones （β-hydroxyisovaleryl shikonin， rhein， lucidone， etc.） can inhibit the proliferation， invasion and migration of pancreatic cancer cells， regulate autophagy and apoptosis， and then inhibit the pathological process of pancreatic cancer by inhibiting PI3K/Akt signaling pathway.