29 results about "SMAD" patented technology

The application discloses a use of a solute carrier family 25A33 gene in preparation of a medicament for treating presbycusis, and the use is achieved by enhancing SLC25A33 expression on an endolymphatic vascular stripe, by maintaining mitochondrial function stability of pericyte cells around the vascular stripe, by reducing active oxygen free radical (ROS) generation, and by blocking TGFbeta / SMAD pathway-mediated pericyte differentiation, so as to protect the integrity of the blood labyrinth barrier. Animal experiments show that overexpression of SLC25A33 can significantly reduce the hearing threshold of a presbycusis model mouse, protect the structure of the blood labyrinth barrier, and improve the expression of tight junction proteins, and the SLC25A33 gene has the potential to treat presbycusis.

The invention discloses an AI intervention analysis method for diabetic renal interstitial fibrosis, and relates to the technical field of biologication.The method comprises the following specific steps of sample collection and multi-omics data acquisition, specifically, kidney tissue samples of diabetic renal interstitial fibrosis patients before and after the diabetic renal interstitial fibrosis patients use glucose kidney health intervention and kidney tissue samples of healthy contrasts are collected; respectively acquiring epigenetic data and single-cell gene expression data, preprocessing, and integrating to construct a comprehensive data set; by combining the AI technology and the high-throughput epigenetic detection technology, the epigenetic modification change on a TGF-beta1 / Smads signal path in the process of intervening diabetic renal interstitial fibrosis by the Sushenkang can be deeply analyzed; a brand-new perspective is provided for understanding the occurrence mechanism of the diabetic renal interstitial fibrosis disease and the drug action mechanism of the TGF-beta1 / Smads pathway, epigenetic data is deeply mined through AI, and the specific mechanism of the TGF-beta1 / Smads pathway related gene expression affected by the TGF-beta1 / Smads pathway through epigenetic regulation is shown.

This invention discloses a sophoridine tricyclic derivative or its pharmaceutical salt, with the following general structural formula: R1 is selected from hydrogen, C1-C20 straight-chain alkyl, and C1-C20 branched alkyl. In vitro experiments have verified that the sophoridine tricyclic derivative can inhibit TGF-β-induced activation of hepatic stellate cells, improve CCl4- and bile duct ligation-induced liver injury and liver fibrosis in mice, inhibit TGF-β / Smads signaling pathway activation, and also inhibit diethylnitrosamine-induced primary liver cancer in mice. Therefore, this invention provides new evidence for the treatment, alleviation, or improvement of liver fibrosis or primary liver cancer using sophoridine tricyclic derivatives.

The invention discloses an application of butyric acid or a derivative thereof in preparation of a zearalenone reproductive toxicity resisting preparation. Also disclosed is an antitoxic feed composition comprising a specific base ration and a butyric acid derivative. In-vivo and in-vitro tests and molecular mechanism researches prove that butyric acid and derivatives thereof (such as tributyrin and sodium butyrate) can effectively relieve zearalenone (ZEN)-induced animal ovary injury. The action mechanism of the traditional Chinese medicine composition is that follicular atresia is reduced, the balance of reproductive hormones (such as GnRH, E2, AMH and P4) is recovered, and clinical symptoms caused by ZEN poisoning such as vulva swelling and the like are relieved by activating a BMPs / SMAD signal channel, especially up-regulating SMAD4 protein expression and inhibiting oxidative stress (ROS) and Caspase-3 mediated granular cell apoptosis.

The invention discloses a TGF-beta / Smad signal channel inhibitor. The TGF-beta / Smad signal channel inhibitor is prepared from the following components in parts by mass: 1000 parts of tea oil, 0.09 to 9.8 parts of bakuchiol and 0.01 to 0.2 part of acetyl hexapeptide-8, the invention also discloses a method for preparing the TGF-beta / Smad signal channel inhibitor as described above. The invention also discloses a cosmetic, which contains the TGF-beta / Smad signal channel inhibitor as an active component. The invention further discloses a method for evaluating the anti-aging effect of the cosmetic. According to the composition, by inhibiting abnormal activation of a TGF-beta / Smad signal channel, excessive deposition and crosslinking of an extracellular matrix are reduced, meanwhile, synthesis of collagen and elastin is promoted, aging characterization such as skin laxity and wrinkles is effectively improved, and deep repair and rejuvenation remodeling of skin aging damage are achieved.

The invention belongs to the technical field of medical chemistry, and particularly relates to a polycyclic polyketone derivative as well as a preparation method and application thereof in treating hepatic fibrosis. Six polycyclic polyketone compounds are obtained from a fungus M. arundinis HL1 separated from a marine sample in Huilaxian County, Guangdong Province, the series of compounds can significantly inhibit expression of FN, Collagen I, alpha-SMA and other fibrosis-related factors in hepatic stellate cells LX-2, and the compound 2 has a significant inhibition effect at a concentration of 40 [mu] mol / L and has no significant toxicity. And the compound 2 reduces the p-Smad2 / 3 level through dose dependence, does not influence the total Smad2 / 3 level, and plays an anti-fibrosis role by inhibiting a TGF-beta / Smad signal channel. The series of compounds, especially the compound 2, are expected to become anti-hepatic fibrosis candidate drugs, and provide a brand new chemical skeleton for research and development of low-toxicity and high-efficiency anti-hepatic fibrosis drugs.

The method for producing a cell aggregate including glial progenitor cells according to the present invention comprises:(1) a step of subjecting pluripotent stem cells to suspension culture in an embryoid-body-forming culture medium containing one or more SMAD signaling inhibitors and one or more Wnt signaling activators in the absence of feeder cells for 5 days to 10 days, to form a cell aggregate;(2) a step of subjecting the cell aggregate obtained in (1) to suspension culture in an embryoid-body-forming culture medium containing retinoic acid;(3) a step of subjecting the cell aggregate obtained in (2) to suspension culture in an embryoid-body-forming culture medium or neuron-and-glia-proliferating culture medium containing retinoic acid and one or more SHH signaling activators; and(4) a step of subjecting the cell aggregate obtained in (3) to suspension culture in a neuron-and-glia-proliferating culture medium containing no retinoic acid and one or more SHH signaling activators.

Provided are: an improved culture medium composition which can be used for culturing pluripotent stem cells of mammals, preferably for establishing and maintaining pluripotent stem cells of mammals useful for producing cultured meat for cattle, pigs, or the like; and a culture method using the culture medium composition. The culture method according to the present invention comprises a step of culturing pluripotent stem cells of mammals in a culture medium composition, the culture medium composition being a culture medium composition for culturing pluripotent stem cells of mammals, the culture medium composition being a serum-free culture medium containing (1) a CDK8 / 19 inhibitor, (2) a ROCK inhibitor, (3) a SMAD activator, and (4) a STAT3 activator.

This invention belongs to the field of medicine, specifically disclosing a drug-loaded biomimetic nanodecoy based on genetic engineering, its preparation method, and its application. The drug-loaded biomimetic nanodecoy of this invention comprises CCR2-overexpressing nanovesicles, and the hydrophobic regions of the nanovesicles are loaded with curcumin. This invention also provides a method for preparing the drug-loaded biomimetic nanodecoy based on genetic engineering and its application. The overexpressed CCR2 is used to adsorb excess CCL2 to inhibit the binding of macrophages to CCL2, preventing macrophage chemotaxis and subsequent TGF-β production. This inhibits the activation of hepatic stellate cells by removing pro-fibrotic mediators upstream; simultaneously, curcumin is released to block the downstream TGF-β / Smad signaling pathway, thereby inhibiting the activation of hepatic stellate cells.

The invention discloses an application of glutathione peroxidase 3 as a therapeutic target in preparation of a medicine for treating pulmonary fibrosis, and an application of a compound Ebselen in preparation of a medicine for treating pulmonary fibrosis. Through single cell and space transcriptomics analysis, it is found for the first time that expression of GPX3 in pulmonary fibrosis patients and model animal lung tissues is significantly reduced. In-vivo and in-vitro experiments prove that up-regulation of GPX3 expression can effectively inhibit fibroblast activation, migration, proliferation and oxidative stress and block a TGF-beta1 / Smad signal channel, so that collagen deposition and pulmonary fibrosis pathological change are relieved. Furthermore, a GPX3 simulant Ebselen is given by adopting an aerosol inhalation mode, is preferably loaded in liposome, and shows a remarkable anti-fibrosis effect in two mouse pulmonary fibrosis models induced by bleomycin and silicon dioxide. The invention provides a brand-new therapeutic target and a medicine scheme with clinical transformation potential for pulmonary fibrosis.

The invention relates to the technical field of TGF-beta regulating peptides, in particular to a TGF-beta regulating peptide as well as a composition, a product and application thereof. The amino acid sequence of the TGF-beta regulating peptide disclosed by the invention comprises (a) any one of the amino acid sequences shown as SEQ ID NO. 1-SEQ ID NO. 20, (b) any one of the amino acid sequences shown as SEQ ID NO. (b) amino acid sequences which are obtained by modifying the N end and / or the C end of the TGF-beta regulating peptide limited by (a) and have the same or similar functions. The TGF-beta regulating peptide provided by the invention can effectively activate a TGF-beta / Smad signal channel, promote the synthesis of collagen and inhibit the generation of sebum, has the effects of resisting skin aging and regulating grease secretion, and has a wide application prospect in the fields of medicines, foods and cosmetics.

The invention discloses a radix ophiopogonis decoction anti-pulmonary fibrosis active component separated based on a centrifugation-membrane dialysis method and application of the radix ophiopogonis decoction anti-pulmonary fibrosis active component. Belongs to the field of ophiopogon root soup. The invention aims to solve the problem that the research on the ophiopogon root decoction mostly focuses on component analysis, pharmacological effect and the like in the prior art. The precipitation phase state, CP-I, CP-II and true solution phase state of the ophiopogon root decoction are successfully separated by adopting a centrifugation-membrane dialysis method. The results of qualitative and quantitative analysis of chemical components show that CP-I is closer to D, D, CP-I can more effectively improve PF symptoms compared with CP-II, and D, CP-I and CP-II do not cause damage to A549 cells and inhibit proliferation of the A549 cells induced by TGF-beta1 to different degrees. Compared with CP-II, the D and CP-I can more remarkably inhibit phosphorylation of protein Smad2 / 3, and the D, CP-I and CP-II can weaken the EMT of A549 cells induced by TGF-beta1 by blocking a TGF-beta1 / Smad pathway. CP-I is an effective phase state of the ophiopogon root decoction.

The invention provides application of irisin and resveratrol in preparation of a preparation for preventing and / or treating radiation-induced lung injury, and belongs to the technical field of biological medicine. The invention finds that combined use of irisin and resveratrol shows a remarkable synergistic effect in the aspects of reducing the radiation-induced oxidative stress level and inflammatory response, and the effect is superior to that of single use of irisin and resveratrol. According to the combination scheme, the inflammation stage and the fibrosis stage of the radiation-induced lung injury are intervened at the same time, the inflammatory reaction is relieved, and meanwhile the fibrosis process is inhibited by adjusting a TGF-beta1 / Smad signal channel. Besides, irisin serving as an endogenous polypeptide and resveratrol serving as a natural product have good safety, so that the immunosuppression risk caused by a large dose of hormone can be avoided.

The invention provides application of an LRG1 inhibitor or a miR-145-5p nano-complex in preparation of a medicine for preventing and / or treating prostatitis, and belongs to the technical field of biological medicine manufacturing. The invention discloses application of an LRG1 inhibitor in preparation of a medicine for preventing and / or treating prostatitis. In order to further improve the stability and the delivery efficiency of the miR-145-5p in vivo when the miR-145-5p is used as an LRG1 inhibitor, the invention provides a miR-145-5p nano-composite which is a polymer nano-particle loaded with the miR-145-5p. According to the invention, through targeted down-regulation of LRG1 and regulation and control of a TGF-beta / Smad signal channel, polarization of macrophages from M1 to M2 is remodeled, and oxidative stress of prostate tissues is synchronously relieved, so that mandatory treatment of prostatitis is realized.

The invention relates to a preparation method and application of serum exosome miR-98-5p of an asthma patient, and belongs to the technical field of biological medicine and molecular biology. The preparation method of the serum exosome miR-98-5p of the asthma patient comprises the following steps: S1, collecting the serum of the asthma patient, heating to quickly melt a sample, then performing centrifugal treatment, taking supernate, filtering by a filter membrane, and collecting filtrate; s2, the filtrate is subjected to centrifugal treatment, supernate is removed, and an exosome crude extract is obtained; s3, the exosome crude extract is subjected to centrifugal treatment after being resuspended, supernate is removed, resuspension is conducted, and the serum exosome of the asthma patient is obtained. According to the present invention, BEAS-2B cells are treated by using the serum exosome of an asthma patient, a miR-22-3p mediated TGF-beta / SMAD pathway is down-regulated to participate in cell epithelial-mesenchymal transition, and proliferation and migration of lung epithelial cells BEAS-2B are promoted;

The present application relates to the technical field of biological medicine, and particularly relates to a nitrile glycoside compound, a preparation method thereof and application of the nitrile glycoside compound in preventing and / or treating kidney disease. A structural formula of the nitrile glycoside compound is shown as follows: wherein R is selected from hydrogen, substituted rhamnose, glucose, substituted glucose, mannose and substituted mannose; the substituents on the substituted rhamnose, the substituted glucose and the substituted mannose are independently selected from formyl, acetyl, propionyl, butyryl, C1-C6 alkyl, C1-C6 alkoxy, halogen, sulfonic acid group or amino; and the substituents on the substituted rhamnose, the substituted glucose and the substituted mannose are located at 2 and 4 positions of a monosaccharide cyclic structure. The present application shows that the nitrile glycoside compound can relieve diabetic nephropathy by driving metabolic reprogramming and a PFKFB3 / TGF-beta / Smads pathway, and has a good treatment effect.

The invention discloses a composition for preventing pressure fine and soft hair and alopecia and promoting hair growth. The composition comprises the following components: EGCG (epigallocatechin gallate), biotin and palmitoyl tripeptide-1. The composition provided by the invention is applied to preparation of cosmetics or medicines for preventing pressure fine and soft hair and pressure alopecia or promoting hair growth. According to the composition, hair follicle fibrosis is inhibited by inhibiting a TGF-beta / smad signal channel, keratin synthesis is increased to improve hair fineness and softness, a BMP signal channel is activated to improve hair follicle miniaturization, hair follicle and hair growth is promoted, the synergistic effect is achieved, the remarkable anti-hair-loss effect is achieved, and toxic and side effects are avoided.

The application belongs to the field of biological medicine, and provides application of TGF-beta / Smad signal pathway in treatment of corneal neovascularization after corneal alkali burn. The application proves that by inhibiting the TGF-beta / Smad signal pathway, the alkali burn-induced corneal neovascularization can be significantly reduced, and the corneal pathological damage is improved, and the mechanism of action involves regulating M2 type macrophage polarization and inhibiting the process of cellular ferroptosis of corneal tissue. It is found that by using a specific inhibitor SB-431542, the expression of TGF-beta1 and p-Smad2 / 3 proteins can be effectively reduced, the angiogenic factors such as VEGFA and CD31 are reduced, the inflammatory factors such as IL-4 and IL-10 are down-regulated, the GSH level is restored, and the Fe 2+ and MDA contents are reduced. The application is suitable for developing a targeted therapeutic drug for pathological neovascularization after corneal alkali burn, and provides a theoretical basis.

The invention relates to the field of medical instruments, in particular to a device for resisting penis cavernous body fibrosis and application, the device comprises magnets arranged in pairs and a driving mechanism for driving the magnets to rotate so as to generate a rotating magnetic field capable of inhibiting the penis cavernous body fibrosis process, and the device further comprises a control device used for containing a tested object and used for controlling the penis cavernous body fibrosis process. And the cabin body enables the tested object to be in an effective action area of the rotating magnetic field. According to the rotating magnetic field intervention device provided by the invention, a non-intrusive physical intervention field aiming at deep soft tissues can be generated through the combination of the paired magnets and the driving mechanism, so that a new hardware platform is provided for resisting penis cavernosum fibrosis; the rotating magnetic field generated by the device is proved to be capable of specifically inhibiting a fibrosis core signal channel TGF-beta / Smad, has the function of adjusting the balance of inflammatory factors, effectively reduces the protein expression level of related signal molecules, and intervenes in the fibrosis process from the molecular level.

This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a mulberry bark extract for treating chronic kidney disease, its preparation method, and its uses. The mulberry bark extract of this invention is obtained by extracting mulberry bark with a 75-100% (v / v) ethanol aqueous solution, concentrating the extract, and drying it. This invention is the first to experimentally discover that the ethanol extract of mulberry bark has significant TGF-β / Smad signaling inhibitory activity. Based on this, a new pharmaceutical use for mulberry bark and its ethanol extract is provided for inhibiting renal TGF-β signaling, suppressing renal fibrosis, and improving renal function, showing great application potential.

In the present invention, we identified the hepatokine FGL1 as a previously unreported hepcidin suppressor that is highly induced in the liver in response to hypoxia during recovery from anemia and in thalassemia mice. We demonstrated that FGL1 is a potent suppressor of hepcidin in vitro and in vivo. Deficiency of Fgl1 in mice (Fgl1- / -) results in lower hepcidin repression after hemorrhage. Finally, we clearly demonstrated that FGL1 is a BMP antagonist that directly binds to BMP6 and impairs the canonical BMP-SMAD signaling cascade that controls hepcidin regulation. Therefore, the present invention relates to methods for preventing or treating iron overload-related diseases by targeting the hepatokine FGL1, a novel hepcidin repressor.

The present invention relates to a use of TSG6 shRNA as a therapeutic agent for metastatic solid cancer. More specifically, the present invention can be usefully used for treating cancer in which metastasis occurs by PLK1, which is known to be overexpressed, particularly in cancer, and the active form thereof or TGF-beta / Smad signaling by reducing proliferation, migration, and invasiveness of metastatic cancer cells through gene therapy that suppresses TSG6 mRNA expression.

The invention discloses an application of a fortune euonymus herb chemical fiber formula in treatment of hepatic fibrosis, and relates to the field of biological medicines. According to the present invention, the anti-hepatic fibrosis effect is provided by inhibiting hepatic stellate cell activation and reducing extracellular matrix deposition, and the hepatic fibrosis is the chronic liver injury pathological stage caused by viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease or drug-induced liver injury; in an in-vitro experiment, the euonymus fortunei chemical fiber formula also plays a role in resisting hepatic fibrosis by inhibiting a transient receptor potential vanillic acid subtype 4 signal channel. The method has the following comprehensive advantages that (1) HSC activation and ECM deposition are inhibited through multi-component and multi-target cooperation; (2) key signal channels such as TGF-beta1 / Smad, TRPV4 and the like can be regulated and controlled at the same time; (3) liver function indexes are obviously improved, and tissue structure damage is relieved; and (4) the medicine is natural in source, high in safety and suitable for long-term application.

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. The efficient derivation of cranial placodes from human pluripotent stem cells is disclosed where the timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Further fate specification at the pre-placode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers and anterior pituitary hormone-producing cells that upon transplantation produce hormones including, but not limited to, human growth hormone and adrenocortiocotropic hormone in vivo. Alternatively, anterior pituitary hormone-producing cells are generated in cell culture systems in vitro.

The invention provides a new medicine for treating gastric cancer, opens up a brand new application field of an alpha-glucosidase inhibitor, and provides a potential effective, safe and economical new treatment scheme for patients with gastric cancer; the invention also discloses a brand new anti-gastric cancer action mechanism of the alpha-glucosidase inhibitor, phosphorylation of PPP1CA at a T320 site is inhibited by down-regulating expression of a tumor inhibition factor RASAL2, and finally inactivation of a downstream p38 MAPK signal channel and a downstream Smad signal channel (a key medium of a TGF-beta channel) is caused. Expression of key genes related to tumor stem cell characteristics (LGR5, CD44 and SOX9), transcription factors (BACH1) and immune escape (PD-L1) is reduced through inhibition of the pathways, so that the effects of inhibiting proliferation of gastric cancer cells and reducing the malignancy degree of the gastric cancer cells are achieved.

Anemia, defined as a reduction in the amount of functional red blood cells in circulation, is a major cause of disease affecting one-third of the world's population. Iron is essential for hemoglobin, the functional component of red blood cells, to store and transport oxygen. Hepcidin, a liver-derived peptide, is a key regulator of iron homeostasis. During anemia, the erythropoietic hormone erythroferon regulates hepcidin synthesis to ensure an adequate supply of iron to the bone marrow for red blood cell synthesis. However, accumulating evidence suggests that other factors may perform a similar function. We identified the hepatokine FGL1 as a previously undescribed hepcidin suppressor that is highly induced in the liver in response to hypoxia during recovery from anemia and in thalassemia mice. We demonstrated that FGL1 is a potent hepcidin suppressor in vitro and in vivo. Deletion of Fgl1 in mice blunts hepcidin suppression after hemorrhage.Finally, FGL1 is a BMP antagonist that directly binds to BMP6 and impairs the BMP-SMAD signaling cascade that controls hepcidin regulation.Therefore, the present invention relates to an FGL1 polypeptide for use in treating patients suffering from iron deficiency-related diseases.

The invention relates to the field of biological medicine application, and provides copper-doped carbon dots for antibiosis and osteogenesis as well as a preparation method and application of the copper-doped carbon dots, and the copper-doped carbon dots are obtained by doping monovalent copper ions on the surfaces of carbon dots with negative charges through a microwave-assisted hydrothermal method; the content of the monovalent copper ions in the copper-doped carbon dots is 3%-10%. The copper-doped carbon dots have ROS generation mediated copper-like death-like antibacterial performance, and show obvious surface negative charges, so that electrostatic interaction between the copper-doped carbon dots and mesenchymal stem cells can be triggered, downstream activation of a BMP / SMAD pathway is triggered, and the BMP / SMAD pathway is activated. The negative charges promote osteogenic differentiation, Cu-triggered copper-like death and the synergistic antibacterial effect of CDT, so that the infectious bone defect of the skull can be completely healed after 2 months.

This invention provides a triptolide sustained-release hydrogel targeting the FOSB and TGFB1 axes and its applications, belonging to the field of biomedical materials and drug delivery technology. The sustained-release hydrogel is a core-shell structured sequential release hydrogel. The outer layer is a 40 mg / mL low-concentration gelatin methacrylamide hydrogel loaded with stromal cell-derived factor-1α (SDF-1α), and the inner layer is a 60 mg / mL high-concentration GelMA hydrogel loaded with triptolide. This invention is the first to clearly demonstrate that the transcription factor FOSB constitutes a core driving pathway for endometriosis fibrosis by transcribing and activating TGFB1. Triptolide can directly bind to FOSB and promote its ubiquitination-mediated degradation, thereby blocking the TGF-β / Smad signaling pathway and mesenchymal-myofibroblast transformation. Through a synergistic recruitment-targeted inhibition strategy using core-shell hydrogels, SDF-1α rapidly recruits myofibroblasts in the lesion area, and tripterygium wilfordii achieves local sustained release over 14 days. While significantly inhibiting fibrosis and reducing the size of endometriosis lesions, it avoids the hepatotoxicity and off-target damage of free drugs.

The invention discloses an application of methyl coptisine in preparation of an anti-pulmonary fibrosis medicine. In-vivo and in-vitro experiments prove that methyl coptisine can remarkably improve pathological manifestations of bleomycin-induced pulmonary fibrosis in mice, reduce collagen deposition and increase the survival rate, and the action mechanism of methyl coptisine is that the methyl coptisine can doubly inhibit activation of TGF-beta1 / Smad and NF-kappa B signal channels and reverse expression of fibrosis key markers. The invention provides a new candidate drug for treatment of pulmonary fibrosis, and has great clinical application value.