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Biomedical subjects

Hao Fang

Publications and source records attributed to Hao Fang.

18 recordsLinked to original sources
PubMed2026

Targeting SIRT6: the design and therapeutic implications of activators and inhibitors.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacylase that maintains genomic stability, regulates metabolism, and influences aging, making it an attractive but challenging therapeutic target. Pharmacological modulation of SIRT6 holds promise for cancer and metabolic disorders, yet its context-dependent functions demand precise intervention strategies. Potent, selective, and drug-like chemical probes are therefore essential to dissect SIRT6 biology and to validate its therapeutic potential. This review critically evaluates recent medicinal chemistry advances in SIRT6 modulation. We focus on structure-guided design strategies and structure-activity relationships (SAR) that have transformed initial hits into optimized leads for both activators and inhibitors, highlighting the remaining challenges in achieving isoform selectivity and drug-like properties.

Sirtuins↗
PubMed2026

Covalent warheads as a versatile platform for molecular glue development.

Targeted protein degradation (TPD) has become a novel therapeutic modality for diseases in drug discovery. Most progress on TPD has focused on the ubiquitin proteasome system; however, only a handful of >600 human genome-encoded E3 ligases have been successfully applied. Expansion of the E3 ligase toolbox with novel E3 ligases and their ligands will broaden the potential applications of TPD. Besides that, covalent molecular glue degraders (MGDs) provide a promising direction for TPD. Covalent MGDs may offer several advantages, including increased selectivity, broad applicability to traditionally undruggable proteins, and efficient protein degradation. This review systematically summarizes the latest progress in the field of covalent MGDs, focusing on validated E3 ligases and their corresponding covalent warheads. Structural features, modes of action, and design strategies of covalent MGDs are discussed aiming to provide guidance for the development of novel covalent MGDs.

Journal Article↗
PubMed2026

The Mechanism of Celosiae Semen in the Treatment of Diabetic Cataract: Based on Network Pharmacology.

INTRODUCTION: Diabetes mellitus can be complicated by a variety of ocular diseases, among which the postoperative complications of diabetic cataract (DC) are significantly higher than those of non-DC patients. Therefore, finding drugs with natural active ingredients is an urgent challenge in the prevention and treatment of DC. Discovering the potential molecular mechanism of celosiae semen (CS) for the treatment of DC and providing new ideas and programs for the treatment and prevention of DC. METHODS: In this study, network pharmacology, molecular docking, and molecular dynamics simulations were utilized to predict the binding and functional enrichment of the main active ingredients of CS with DC-related targets, and to explore the potential pathways and mechanisms of CS for the treatment of DC. RESULTS: Through database searching and screening, a total of 45 potential targets of CS for the treatment of DC were identified, functionally enriched, and a protein-protein interaction network was constructed, and the key target, SRC, was finally found. The results of molecular docking and molecular dynamics simulation showed that the main active ingredient of CS, stigmasterol, could bind stably to the key target SRC protein. DISCUSSION: This study not only elucidates the phyto-pharmacological basis of CS in DC management but also provides a framework for developing natural product-derived targeted therapies against diabetic ocular complications. The integration of modern genomics and computational chemistry to deconstruct the therapeutic effects of traditional Chinese herbal medicines has great clinical significance in expanding the scope of traditional Chinese medicines for the treatment of DC and promoting precision targeting. However, this requires verification through basic experiments. CONCLUSION: These computational findings suggest that CS may exert its anti-cataract effects through the multi-target modulation of diabetic metabolic pathways and SRC-mediated signaling cascades.

Humans↗
PubMed2006

Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors.

A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the l-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC(50)=5.2-9.7nM) and could be used as lead compounds in the future.

Caffeic Acids↗
PubMed2006

Anaphylactic reaction induced by Toxoplasma gondii-derived heat shock protein 70.

Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) is a virulent molecule specific for tachyzoites of T. gondii. The expression of T.g.HSP70 rapidly increases just before death of the host, indicating that T.g.HSP70 functions as a danger signal during lethal acute T. gondii infection. In the present study, T.g.HSP70 was proven to be capable of inducing lethal anaphylactic reaction in T. gondii-infected wild-type (WT) mice. Anaphylactic reaction appeared within the first hour after intraperitoneal injection of T.g.HSP70 and was characterized by a series of consequent symptoms until death. T.g.HSP70-induced anaphylactic reaction was not observed in IFN-gamma knockout (GKO) mice, indicating the involvement of IFN-gamma in the reaction. The anaphylactic reaction was transferable to GKO mice by splenocytes but not serum from infected WT mice. Also, this reaction occurred in B cell-deficient mice, indicating that T.g.HSP70-induced anaphylactic reaction occurred through an Ig-independent pathway. The messenger RNA (mRNA) expression of IFN-gamma increased significantly in splenocytes from T. gondii-infected WT mice after T.g.HSP70 injection. Furthermore, the mRNA expression of platelet-activating factor (PAF) acetylhydrolase in WT, but not GKO mice, distinctly increased during the occurrence of T.g.HSP70-induced anaphylactic reaction, indicating the involvement of PAF in T.g.HSP70-induced anaphylactic reaction. Treatment with PAF receptor antagonist rescued WT mice from the anaphylactic reaction. These data demonstrated the involvement of IFN-gamma-dependent PAF activation in T.g.HSP70-induced anaphylactic reaction.

Anaphylaxis↗
PubMed2006

Toxoplasma gondii-derived heat shock protein 70 stimulates maturation of murine bone marrow-derived dendritic cells via Toll-like receptor 4.

Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) induced maturation of bone marrow-derived dendritic cells (DCs) of wild-type (WT) C57BL/6 mice as evidenced by an increase in surface expression of MHC class I and II molecules and costimulatory molecules such as CD40, CD80, and CD86. Functionally, decreased phagocytic ability and increased alloreactive T cell stimulatory ability were observed in T.g.HSP70-stimulated DCs. These phenotypic and functional changes of T.g.HSP70-stimulated DCs were demonstrated in Toll-like receptor (TLR) 2- and myeloid differentiation factor 88 (MyD88)-deficient but not TLR4-deficient C57BL/6 mice. DCs from WT and TLR2-deficient but not TLR4-deficient mice produced IL-12 after T.g.HSP70 stimulation. T.g.HSP70-stimulated DCs from WT, TLR2-deficient, and MyD88-deficient, but not TLR4-deficient mice expressed IFN-beta mRNA. Thus, T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88-independent signal transduction cascade.

Animals↗
PubMed2006

[Immunohistochemical study of heme oxygenase-1 expressed in human normal dental pulp cell and tissue].

OBJECTIVE: To study the expression of heme oxygenase-1 (HO-1) in dental pulp tissue and to find out the relationship of distribution and function of HO-1. METHODS: 30 pulp tissues were obtained from clinically extracted human healthy premolars and third molars. The expression of HO-1 in dental pulp was detected by means of SABC immunohistochemical technology. RESULTS: HO-1 immunoreactivity was observed in vascular endothelial cells, odontoblasts and some fibroblasts cells. CONCLUSION: The distribution of HO-1 in normal human dental pulp suggests that HO-1 may play an important role in pulp flow regulation, dentin production and its calcifying; it also may play some roles in dental pulp cells metabolism and differentiation.

Cell Differentiation↗
PubMed2005

Pharmacophore-based design, synthesis, biological evaluation, and 3D-QSAR studies of aryl-piperazines as alpha(1)-adrenoceptor antagonists.

Phenyl-piperazines were designed and synthesized based on pharmacophore for uro-selective alpha(1)-adrenoceptor antagonists and 3D chemical database searching. Within this series, three compounds, 2, 3, and 13, showed similar or better alpha(1)-AR antagonistic activity compared with prazosin. The 3D-QSAR study of these compounds may provide useful information for the development of novel aryl-piperazines as uro-selective alpha(1)-adrenoceptor antagonists, which can be used for the treatment of BPH with fewer side effects.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

Boronolectins and fluorescent boronolectins: an examination of the detailed chemistry issues important for the design.

Glycans in the form of glycoproteins or glycolipids play very critical roles in various biological and pathological processes including inflammation, cancer metastasis, immune reactions, embryo development, cell-cell communications and adhesions, blood generation, etc. Proteins (lectins) that can recognize carbohydrates have played very important roles in studying glycobiology. Small molecule mimics of lectins will be very useful in the development of new therapeutics and diagnostics. Along this line, boronic acids have been widely used in the design and synthesis of small organic compounds that mimic the function of lectins. This review examines in detail the factors that are important for the design of boronic acid-based lectin mimics, boronolectins.

Animals↗
PubMed2005

A novel B-2 suppressor cell regulating susceptibility/resistance of mice to Toxoplasma gondii infection.

Irradiation treatment enhanced resistance of C57BL/6, but not BALB/c against Toxoplasma gondii infection. Six Gy-irradiated (IR) C57BL/6 recipients of B-2 cells from T. gondii-infected C57BL/6 died after infection. B-2 suppressor cells from infected C57BL/6 enhanced production of IL-4 and IL-10 in peritoneal exudate cells (PECs), and down-regulated NO release in peritoneal macrophages after infection. On the other hand, B-2 suppressor cells were not detected in a strain, BALB/c, resistant against infection. These data indicated that irradiation-sensitive B-2 cells regulated susceptibility/resistance in mice against T. gondii infection.

Animals↗
PubMed2005

Toll-like receptor 4 mediates tolerance in macrophages stimulated with Toxoplasma gondii-derived heat shock protein 70.

Peritoneal macrophages (PMs) from toll-like receptor 4 (TLR4)-deficient and wild-type (WT) mice were responsive to recombinant Toxoplasma gondii-derived heat shock protein 70 (rTgHSP70) and natural TgHSP70 (nTgHSP70) in NO release, but those from TLR2-, myeloid differentiation factor 88 (MyD88)-, and interleukin-1R-associated kinase 4 (IRAK4)-deficient mice were not. Polymyxin B did not inhibit PM activation by TgHSP70 and nTgHSP70 from WT and TLR4-deficient mice, while it inhibited PM activation by lipopolysaccharide. Pretreatment of PMs from WT but not from TLR4-deficient mice with rTgHSP70 resulted in suppression of NO release on restimulation with rTgHSP70. Similarly, pretreatment of PMs from WT but not TLR4-deficient mice with nTgHSP70 resulted in suppression of NO release on restimulation with nTgHSP70. Polymyxin B did not inhibit rTgHSP70- and nTgHSP70-induced tolerance of PMs from TLR4-deficient mice. Furthermore, PMs from WT mice increased suppressor of cytokine-signaling-1 (SOCS-1) expression after restimulation with rTgHSP70, while those from TLR4-deficient mice did not. Phosphorylation of JNK and I-kappaBalpha occurred in rTgHSP70-induced tolerance of PMs from TLR4-deficient mice, but not in that from WT mice. These data indicated that TgHSP70 signaling mechanisms were mediated by TLR2, MyD88, and IRAK4, but not by TLR4. On the other hand, signaling of TgHSP70-induced tolerance was mediated by TLR4, and the expression of SOCS-1 suppressed the TLR2 signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies and lupus nephritis. In the present study using New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZBW F1) mice, we planned to investigate the effects of Toxoplasma gondii infection on the progress of lupus nephritis. Female NZBW F1 mice at the age of 2 months were perorally infected with T. gondii. The T. gondii infection reduced the number of mice developing proteinuria and immune complex deposits in their kidneys and prolonged their life span. A marked decrease in the levels of IgM and IgG anti-DNA antibodies, especially IgG2a and IgG3 subclasses, was observed in T. gondii-infected NZBW F1 mice at 9 months of age. The level of anti-HSP70 IgG autoantibody in the sera of NZBW F1 mice was significantly higher than that in control mice at 9 weeks after T. gondii infection. Moreover, NZBW F1 mice treated with anti-self heat shock protein 70 (HSP70) monoclonal antibody were substantially protected against the onset of glomerulonephritis. Further, down-regulation of intracellular expression of IFN-gamma and IL-10 was shown in spleen cells of T. gondii-infected NZBW F1 mice. This was consistent with the previous data indicating the involvement of Th1-type and Th2-type cytokines in the development of lupus-like nephritis. These results suggest that T. gondii infection is capable of preventing the development of autoimmune renal disorder in NZBW F1 mice.

Animals↗
PubMed2004

The design of boronic acid spectroscopic reporter compounds by taking advantage of the pK(a)-lowering effect of diol binding: nitrophenol-based color reporters for diols.

The complex that forms between a boronic acid and a diol is often much more acidic than the starting boronic acid. In conditions where the solution pH is between the two pK(a) values, the boron atom will convert from a neutral trigonal form to an anionic tetrahedral form upon complexation. Such a change is likely to dramatically alter the electron density of neighboring groups. Utilizing this effect, we have designed and synthesized two nitrophenol-based boronic acid reporter compounds that change ionization states and therefore spectroscopic properties upon diol binding. Both compounds show significant UV changes upon addition of saccharides. For example, a blue shift of the absorption max from 373 to 332 nm was observed with the addition of D-fructose to 2-hydroxy-5-nitrophenylboronic acid at neutral pH. Such a reporter compound can be used as a recognition and signaling unit for the construction of polyboronic acid sensors for the selective and specific recognitions of saccharides of biological significance.

Boronic Acids↗
PubMed2004

A quantitative assay method of Toxoplasma gondii HSP70 mRNA by quantitative competitive-reverse transcriptase-PCR.

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) has been identified as a virulent molecule expressing only in T. gondii tachyzoites during lethal acute infection. Therefore, it is of importance to determine the expression of T.g.HSP70 mRNA in a quantitative manner for analysis of virulence of T. gondii in tissues. We have constructed a competitor T.g.HSP70 and have successfully established a quantitative competitive-reverse transcriptase-polymerase chain reaction (QC-RT-PCR) targeting T.g.HSP70 gene. By using the established QC-RT-PCR method, we have demonstrated that the copy number of T.g.HSP70 mRNA per T. gondii tachyzoite was highest in the lung among the organs examined in interferon-gamma knockout (GKO) mice.

Animals↗
PubMed2004

Progress in boronic acid-based fluorescent glucose sensors.

Effective management of diabetes relies on the frequent monitoring of blood glucose concentrations. The current approach of blood sampling and glucose concentration determination in vitro) presents many problems. Therefore, there is a drive for the development of non-invasive and continuous monitoring of glucose concentrations. The use of implanted glucose fluorescent sensors represents a promising approach. Due to its strong interaction with diol moieties, the boronic acid group often plays a critical role in the design of such glucose sensors. This paper reviews the progress in this area during the last ten years.

Alcohols↗
PubMed2004

Roles of Toxoplasma gondii-derived heat shock protein 70 in host defense against T. gondii infection.

C57BL/6 mice receiving intraperitoneal injection of Toxoplasma gondii -derived heat shock protein 70 (T.g. HSP70) on day 3 post T. gondii infection succumbed by day 9 post infection, while vector protein-injected control mice survived more than 6 months. The deteriorating effect of T.g. HSP70 on host immune responses was dose-dependent. By T.g. HSP70 injection, T. gondii loads increased in various organs of T. gondii-infected mice. Th2 cytokines such as IL-4 and IL-10 were continuously produced from spleen and peritoneal exudate cells of T. gondii -infected mice by injection of T.g. HSP70. Furthermore, nitric oxide production from peritoneal macrophages in T. gondii-infected mice was reduced by T.g. HSP70.

Animals↗
PubMed2003

Induction of protective immunity by primed B-1 cells in Toxoplasma gondii -infected B cell-deficient mice.

We examined the role of B-1 cells in protection against Toxoplasma gondii infection using B cell-deficient mice (muMT mice). We found that primed but not naïve B-1 cells from wild-type C57BL/6 mice protected B cell-deficient recipients from challenge infection. All muMT mice transferred with primed B-1 cells survived more than 5 months after T. gondii infection, whereas 100% of muMT mice transferred with naïve B-1 cells succumbed by 18 days after infection. Additionally, high expression of both T help (Th) 1- and Th2-type cytokines and a high level of nitric oxide production were observed in T. gondii-infected muMT mice transferred with primed B-1 cells. Thus, it was clearly demonstrated that B-1 cells play an important role in host protection against T. gondii infection in muMT mice.

Adoptive Transfer↗