52 results about "SMAD" patented technology

Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons. The present disclosure also relates to compositions of cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons, and their precursors, that are highly enriched and can be used in variety of application. These cells can be used therapeutically to treat neurodegenerative and neuropsychiatric disorders, and can be used for disease modeling and drug screening.

The instant application provides kits and methods for identifying agents which induce or inhibit the osteogenic effect of LMP or BMP proteins. The kits are directed to methods which measure either an amount of a complex between a Smurf protein or a fragment thereof and an LMP protein or a fragment thereof. Alternatively, the kits are directed to methods of measuring an amount of the ubiquitinated Smad protein or a fragment thereof.

<heading lvl="1">SUMMARY OF THE INVENTION < / heading> The use of gene therapy for the treatment of different kinds of fibrosis in human beings is disclosed. The purpose is the use of "therapeutic2 genes specifically directed to target organs to revert and / or prevent the development of the fibrosis process. The potential application of gene therapy to patients with fibrosis and / or cirrhosis will depend to a large extent on the successful delivery of genes which encode for therapeutic proteins to livers with severe fibrosis and that these genes which encode for proteins human MMP-8 active and latent, MMP-1, MMP-2, MMP-9 and MMP-13; human uPA wild type and / or modified (or its truncated version), the truncated receptor for TGF-beta type II and Smad-7 can be directed by adenovirus and / or other recombinant vectors that cannot transduce (infect) others organs. The recombinant adenoviruses (AdR) are vectors highly efficient for the transduction of therapeutic genes to diverse target cells. We have proved that they can carry genes to cirrhotic livers. The delivery of therapeutic genes through such adenoviral vectors and other recombinant vectors could also be performed using cationic and anionic liposomes (DOTMA). Therefore, we propose the use of this patent to be applied in the same manner to: Renal fibrosis Pulmonary fibrosis Hypertrophic and keloid scars (skin fibrosis), and Other kinds of fibrosis.

Under the knowledge which two kinds of intracellular signal transfer mechanism of TGF-beta super family receptor exist: a pathway via Smad molecule and a pathway via novel MAP kinase such as TAB1 and TAKI, and the knowledge of interaction of Smad molecule with intranuclear receptor or CBP / p300 on the transcription control by Smad molecule, a screening method and a molecular designing method for pharmaceuticals with identified site of action and higher specificity can be accomplished.

The present invention relates to uses of icariin or icariside II, specifically to uses of icariin, icariside II or pharmaceutically acceptable salts thereof in preparation of products for prevention and treatment of kidney diseases, specifically chronic kidney diseases. According to the present invention, with the icariin and the icariside II, the kidney endogenous stem cells of the EdU label can be increased and recruited, the TGF[beta] / Smad, CTGF, P-ERK1 / 2 phosphorylation level can be regulated, the pathological changes of endothelial cells, glomerular basement membrane and kidney tubules can be improved, the proteinuria can be reduced, the urea nitrogen and creatinine clearance level can be improved, the pathological change progression of the chronic kidney disease can be delayed, and the risk of the renal dysfunction can be reduced, such that the icariin and the icariside II can be used for prevention or treatment of kidney diseases.

The invention relates to new application and a new action mechanism of verbascoside, in particular to application of verbascoside in the drugs for treating and preventing type II diabetic nephropathy,and the research on the protection function of the verbascoside for the type II diabetic nephropathy and the action mechanism thereof. Results show that the verbascoside can alleviate liver injury caused by high glucose and lower the serum creatinine, urea nitrogen and urinary microalbuminuria levels, the blood fat level (total cholesterol and triglyceride) and the fasting blood-glucose and bloodinsulin level of spontaneous diabetes db / db mice; TGF (Transforming Growth Factor)-beta 1 and the signal transduction protein Smad3 and Smad4 and alpha-SMA protein expression thereof in a kidney tissue are obviously lowered; meanwhile, the verbascoside can alleviate the liver injury caused by high glucose; HK-2 proliferation and EMT (pithelial-Mesenchymal Transition) formation can be inhibited. In conclusion, the verbascoside has an obvious protection function on the type II diabetic nephropathy, the action mechanism of the verbascoside is that the kidney protection function of the verbascoside is implemented through oxidative stress reaction regulation and control, TGF-beta / smad signaling channel inhibition and kidney fibrosis alleviation.

The invention belongs to the technical field of glioma prognosis markers, and particularly relates to application of BACE2 as a glioma prognosis / treatment marker. According to the invention, the research results prove that high-level BACE2 expression is related to the high-level human brain glioma, the mesenchymal molecule subtype of GBM and the poor prognosis for the first time; furthermore, TGF[beta] 1 stimulates BACE2 expression by means of Smad dependent signal transduction, so as to regulate the activity of TNF-[alpha] induced NF-[kappa] B by means of a PP1 / IKK pathway to promote tumorigenesis in glioma cells. The BACE2 can be used as a novel biomarker and a potential treatment target for treating human brain glioma.

The invention relates to the application of BMP-7 in preparing drugs for preventing and / or treating hepatic fibrosis and belongs to the medical treatment technical field. The preparation comprises the steps of: preparing a hepatic fibrosis model of rats through an animal model experiment and a vitro cell experiment, separating liver cells and hepatic stellate cells of an animal to be tested, observing the affect of bone morphogenetic protein BMP-7 on experimental hepatic fibrosis. The results show that BMP-7 can restrain the activity of a signaling pathway protein Smad 1 / 3 of TGF-beta1 in cells and the expression of TGF-beta1.The results of the animal experiment show that BMP-7 can remarkably prevent and treat experimental hepatic fibrosis.

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.

This invention provides method for repairing, regenerating, treating, or inducing the repair of an injury, a defect or a condition of a connective tissue of a subject. This invention provides a method of regenerating, enhancing, inducing repair and / or development of connective tissue as a result of a defect, injury or condition of the connective tissue of a subject comprising the step of inserting an engineered cell which comprises a nucleic acid encoding a SMAD protein or variant thereof, so as to induce regeneration, repair and / or development of the connective tissue. This invention further provides methods of ex-vivo implantation of engineered cells into an injury, defect or condition of the connective tissue. This invention also provides a nucleic acid encoding a SMAD 8 protein variant, cells comprising such SMAD 8 variant, include mesenchymal stem cells, progenitor cells or cells derived from a connective tissue. Lastly, this invention provides SMAD 8 protein variant.

The invention relates to novel 2'-carbamyl biphenyl compounds and application thereof in anti-hepatic fibrosis medicines. Experimental research proves that the novel 2'-carbamyl biphenyl compounds are capable of obviously restraining generation of collagenous fiber, inhibiting TGFbeta / Smad signal channels, reversing loss of weight, improving liver function and inhibiting ductular proliferation. Therefore, the compounds or compositions comprising the compounds are expected to be developed into anti-hepatic fibrosis medicines with good potential.

A new family of proteins, the SARA proteins, has been identified. These proteins bind to receptor-regulated Smad proteins and modulate signal transduction by TGFβ, activin and bone morphogenetic protein.

The invention provides application of sulforaphane in preparation of a drug for inhibiting and / or treating radioactive muscle fibrosis, and relates to the technical field of biological medicines. The Sulforaphane (SFN) serves as an Nrf2 agonist, can play a role in inhibiting tumors by intervening signal transduction pathways related to oxidative stress, inflammation, cell cycle, proliferation, apoptosis, angiogenesis, metastasis and the like, and can protect various tissues and organs from fibrosis. The SFN can inhibit expression of fibrosis genes by regulating Nrf2-mediated oxidative stress and TGF-beta1 / Smad signal pathways, excessive accumulation of extracellular matrix (ECM) is reduced, and therefore muscle fibrosis caused by radiation is remarkably improved, and the application has certain significance in clinical application in the future.

The invention relates to the technical field of biology, in particular to a gene / small molecule compound complex lipid preparation and a preparation method and application thereof, and particularly relates to a gene / drug composite lipid preparation aiming at a TGF-beta / SMAD signal channel and application thereof. Research finds that a positively charged cationic lipid and a negatively charged nucleic acid drug form a lipid complex through electrostatic interaction, and by means of an active drug loading technology of a small molecule compound, a complex lipid carrier capable of simultaneously delivering a gene drug / small molecule compound into the same target cell can be formed.

The invention relates to application of quinacrine in preparation of a medicine for treating pulmonary fibrosis. A structural formula of the quinacrine is shown in the specification. According to the application, it is found for the first time that the quinacrine can be used for inhibiting Smad2 / 3 phosphorylation through targeting a CUL4B protein, then, a TGF-beta1 / Smads signal transduction pathway is affected, the effect of treating the pulmonary fibrosis is achieved, and the defect that in the prior art, the quinacrine only serves as a sensitizer to participate in a treatment process of cancers such as liver cancer are overcome, so that the application range of the quinacrine is obviously widened.

The invention belongs to the technical field of traditional Chinese medicine application, and particularly relates to application of a tiarella polyphylla alcohol extract in preparation of drugs for treating or protecting and regulating hepatic fibrosis diseases. The application comprises the following steps of: extracting tiarella polyphylla with methanol, heating and refluxing, adding methanol again for reflux extraction, combining extracting solutions, filtering, recovering a solvent under reduced pressure, and performing freeze drying to obtain the tiarella polyphylla alcohol extract. By establishing a mouse hepatic fibrosis model, the tiarella polyphylla alcohol extract is used for administration of high, medium and low doses of the mouse hepatic fibrosis model, and researches find that the tiarella polyphylla alcohol extract has a certain protective effect on CCl4-induced hepatic fibrosis mice, and the effect is related to inhibition of oxidative stress reaction, reduction of inflammatory factor level, regulation of TGF-beta 1 / Smad signal pathway related protein expression, inhibition of HSC activation, reduction of alpha-SMA expression and reduction of collagen synthesis.

The present disclosure relates to the development and use of an immunomodulator that is an antibody or antigen-binding portion thereof that binds to PD-L1. The PD-L1 antibody has high blocking activity on combination of PD-L1 and PD-1, a novel bifunctional antibody formed by the PD-L1 antibody and TGFBR2 can release the anti-tumor activity of T cells by blocking interaction of PD-L1 and PD-1, meanwhile, immunosuppression caused by activation of a smad signal channel by TGF-beta in a tumor microenvironment is effectively blocked, and the anti-tumor activity of the T cells is improved. The induction of effective and lasting anti-tumor immune response in the tumor which is not reacted originally is facilitated.

The invention relates to a pharmaceutical composition for inhibiting myocardial fibrosis, and belongs to the technical field of biological medicines. As the acatinib has relatively high kinase selectivity and relatively good safety, and in a pathological state, BTK in myocardial fibroblasts can be directly combined and phosphorylated with a TGF-beta receptor I (TbetaRI), so that activation of downstream SMAD classical and MAPK non-classical fibrosis signal channels is promoted. The Acalabrutinib can be used for inhibiting phosphorylation and activation of BTK in a targeted manner and reducing the activation of a fibrosis signal channel in a pathological state, so that the occurrence of cardiomyopathy fibrosis is prevented. Therefore, research shows that the BTK inhibitor Acalabrutinib can inhibit myocardial fibrosis reaction under cardiomyopathy conditions (such as myocardial infarction, hypertension, chronic myocardial ischemia and other pathological conditions), so that the cardiac function is protected, adverse cardiac remodeling is prevented, and the occurrence of heart failure is controlled.

The invention provides a structural sequence and a construction method of a fused polypeptide mutant containing a protein transduction domain TAT (Transactivator of Transcription), a Smad anchor and a receptor-activated protein SARA peptide aptamer (SARA / SBD). The fused protein mutant contains 73 amino acids. The protein is subjected to fusion expression and purification, and purified TAT-SARA / SBD is taken as a tested medicament for performing an animal single-side ureteral ligation obstruction model experiment. As proved by a result, the tested medicament has a fibrosis reversing effect. The fused protein mutant can be subjected to efficient supernatant expression, is easy for purifying, is convenient for roducing, and is expected to be applied to treatment of kidney fibrosis.

The invention discloses a preparation method and application of a targeting mesenchymal stem cell (MSC) drug delivery system. The preparation method comprises the steps as follows: S1, stem cell collection; S2, cell detection; S3, production of a transfection mixed solution; S4, pretreatment of MSCs; and S6, alkaline culture. The MSCs are widely sourced, can be xenogenous as well as autogenous andhave sufficient sources, and the cells have excellent capacity in proliferation, survival, differentiation, migration, synthesis, factor secretion and other aspects, are free of ethical problems andhave low immunogenicity and broad application prospects. The disclosed tissue damage targeting MSCs can be effectively planted at tissue damage parts, blood washing or natural falling can be avoided,the homing cell quantity can be increased, besides, low expression of smad protein can be avoided, and the fibrosis promotion risk due to transplantation of the MSCs can be avoided.

The invention disclosed herein generally relates to methods and systems for converting stem cells into specific tissue(s) or cells through directed differentiation. In particular, the invention disclosed herein relates to methods and systems for promoting functional basal-like cells from pluripotent stem cell-derived lung bud tip progenitor organoid tissue through activation of SMAD signaling via activation of TGFβ1 (and / or the TGFβsignaling pathway) and BMP4 (and / or the BMP signaling pathway).

A method for producing a cerebral organoid having amyloid plaques is provided by the invention. The method comprises step (a) for forming, in the presence of an SMAD inhibitor, a germ layer body from a pluripotent stem cell having a mutation in an Alzheimer's disease-related gene; step (b) for, after step (a), embedding the germ layer body in an extracellular matrix, and three-dimensionally culturing the germ layer body in the presence of the SMAD inhibitor and a glycogen synthase kinase 3beta (GSK3beta) inhibitor, to form an organoid; and step (c) for, after step (b), removing the organoid from the extracellular matrix, and culturing the organoid in a culture medium while stirring same, wherein at least a portion of step (c) is performed in the presence of leukemia inhibitory factor (LIF).

The invention discloses preparation and application of a polypeptide for promoting bone regeneration or bone formation. The amino acid sequence of the polypeptide is shown as SEQ ID NO: 1. According to the invention, the tenth to eleventh segments of LRRs motifs are screened from eleventh segments of LRRs motifs of an OMD core protein and are key sites of a complex formed by OMD, BMP2 and a receptor thereof. The polypeptide segment can activate a downstream BMP / SMAD signal channel, reduce the dosage of BMP2 and optimize BMP2 osteogenesis. The polypeptide is small in molecular weight, simple and stable in structure and higher in activity, and can be better applied to promotion of bone injury regeneration and repair.

The invention relates to shRNA and a vector for knocking down a TGF-beta1 (Transforming Growth Factor-beta 1), a kit and application of the shRNA or the vector or the kit. The shRNA disclosed by the invention comprises two oligonucleotide chains; a sequence of the oligonucleotide chain is as shown in SEQ ID NO:9 to 10. The shRNA, the vector or the kit disclosed by the invention can effectively reduce expression of the TGF-beta1 and inhibit expression of the TGF-beta1, CTGF (Connective Tissue Growth Factor) and alpha-SMA and Smads phosphorylation in detrusor smooth muscle cells or urinary bladder from the mRNA level and the protein level so as to effectively inhibit fibrosis of the detrusor smooth muscle cells or the urinary bladder, and has a treatment effect on fibrosis of neurogenic bladder.

The invention belongs to the technical field of medicines, and mainly relates to application of a DOR agonist in preparation of a medicine for resisting renal fibrosis. The application of the DOR agonist is as follows: a1, a2, a3 or a4, a1, preparing a medicine for preventing and / or treating renal fibrosis; a2, prevention and / or treatment of renal fibrosis; a3, activating and / or inhibiting DOR-related cell and molecular signal pathways; and a4, establishing an in-vitro model for activating the DOR so as to prevent and / or treat renal fibrosis. It is found for the first time that by adopting a specific DOR agonist (such as UFP-512) to activate DOR, signal channels such as Smad, p38, Akt and the like can be adjusted, and the specific DOR agonist can act on a transcription factor Snail to regulate and control renal tubulointerstitial transformation (EMT), so that the process of renal fibrosis is relieved. The invention expounds the relationship between the DOR and the renal fibrosis for the first time, reveals that the DOR on the kidney cells is activated to effectively relieve the fibrosis lesion of the kidney cells, provides a new way for preventing and treating the pathological change of the renal fibrosis, and has important scientific value and clinical significance.

The invention provides an application of a compound kushen (radix sophorae flavescentis) injection in preparing a medicine for treating chronic hepatic fibrosis. The compound kushen injection can also be applied in repairing liver injury, and liver tissues are recovered to be normal by inhibiting the deposition of collagen in the liver; in addition, the compound kushen injection can also inhibit activation of hepatic stellate cells, and the medicine is prepared by inhibiting activation of the hepatic stellate cells to treat chronic hepatic fibrosis; the medicine for treating chronic hepatic fibrosis is prepared by down-regulating the expression of hepatic stellate cell activators; the medicine for treating chronic hepatic fibrosis is prepared by selectively inhibiting hepatic stellate cell activation; and the medicine for treating chronic hepatic fibrosis is prepared by intervening activation of a TGF-beta / Smad signal axis in hepatic stellate cells. Compared with the lack of approved drugs for treating hepatic fibrosis in clinic at present, the application of the compound kushen injection disclosed by the invention shows that the compound kushen injection can be used as a promising candidate drug for preventing or treating hepatic fibrosis and preventing the progression of hepatic fibrosis in clinical application.

Methods are provided, in some aspects, for differentiating pluripotent cells into midbrain dopaminergic (DA) neurons using a mono-SMAD inhibition or inhibition of SMAD signaling with only one SMAD inhibitor. In some embodiments, mono-SMAD inhibition utilizes a single inhibitor of bone morphogenic protein (BMP) for differentiating pluripotent cells into midbrain DA neurons.

The invention relates to an application of an extract of a medicinal natural product, in particular to an application of a radix astragali extract. The natural product extract disclosed by the invention is an extract of radix astragali, especially total flavonoids of radix astragali or astragaloside. The radix astragali extract disclosed by the invention can be directly used for preparing the medicine for treating the pulmonary fibrosis disease or used for preparing the compound medicine for treating the pulmonary fibrosis disease. The invention has the following beneficial effects: 1, it is found for the first time that total flavonoids of radix astragali and astragaloside can inhibit polarization of M2 type macrophages and activation of TGF-beta1 / Smads signal channels, and effectively inhibit pulmonary fibrosis; and 2, the medicine is a traditional Chinese medicinal material, is low in price and small in toxic and side effects, can remarkably inhibit the development of pulmonary fibrosis, and is worthy of wide popularization.

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.