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1.
Food Chem ; : 128582, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33199120

RESUMO

The electronic database was searched up to July 2020, using keywords, kenaf and roselle, chemical constituents of kenaf and roselle, therapeutic uses of kenaf and roselle. Journals, books and conference proceedings were also searched. Investigations of pharmacological activities of kenaf revealed that this edible plant exhibits a broad range of therapeutic potential including antioxidant, antimicrobial, antityrosinase, anticancer, antihyperlipidemia, antiulcer, anti-inflammatory, and hepatoprotective activities. Kenaf also showed versatile utility as a functional ingredient in food, folk medicine, and animal nutritions, as well as in nanotechnology processes. The exploitation of underexploited kenaf by-products can be a significant part of waste management from an economic and environmental point of view. In addition, kenaf showed comparable nutritional, phytochemical, and pharmacological properties with Hibiscus sabdariffa (Roselle). This review has important implications for further investigations and applications of kenaf in food and pharmaceuticals industry.

3.
Yi Chuan ; 42(11): 1122-1132, 2020 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-33229318

RESUMO

The processes of self-renewal and differentiation of germ cells are crucial to the development of male infertility and germ cell tumors. CG8005 gene is one of the regulatory factors of the testicular germ stem cells in Drosophila melanogaster, and its functional mechanism is still unknown. To explore the biological function(s) of CG8005 gene in the germ cell niche of Drosophila testis, first, the UAS-gal4 system was used to drive the expression of UAS-CG8005 RNAi in Drosophila testicular germ cells and cyst cells. Fertility tests were then performed to determine the fertility rate of male flies. Second, the expression patterns of Vasa, IBI, Zn finger homeodomain 1 (Zfh1), eyes absent (Eya), DE-cad, FasIII and Phospho-Histone H3(PH3), and TUNEL were analyzed by immunofluorescence staining in both control and CG8005 RNAi testes. Lastly, small interfering RNA (siRNA) was used to silence the CG8005 gene expression in Drosophila S2 cells; and PH3 was used to detect the proliferation ability of Drosophila S2 cells in the control group and CG8005 siRNA group. Apoptosis of Drosophila S2 cells was analyzed with TUNEL and flow cytometry. To observe the relative expression of the spliceosome, the mRNA levels of the spliceosome subunits were detected by fluorescence quantitative RT-PCR. As compared with the control group, the results showed that deletion of the CG8005 gene in the germ cells and cyst cells of the testis reduced or even completely abolished the fertility of male fruit flies. In addition, nos-gal4 driven UAS-CG8005 RNAi led to loss of fusomes and reduce the proliferative ability of germ cells. Noticeably, tj-gal4-directed UAS-CG8005 RNAi knockdown of CG8005 gene in the testis led to germ cell tumor development. Knockdown of CG8005 gene in Drosophila S2 cells resulted in increase in apoptosis and inhibition of proliferation. Further, the silencing of the CG8005 gene in Drosophila S2 cells caused increases in the mRNA levels of the spliceosome subunits. Hence, CG8005 gene is essential for the self-renewal and differentiation of germ cells in Drosophila testis. Its deletion may lead to restricted germ cell survival and the formation of germ cell-like tumors. CG8005 gene can participate in the regulation of proliferation and apoptosis of Drosophila S2 cells, which is essential for the maintenance of cell life, and might competitively regulate the mRNA levels of spliceosome subunits.

4.
Reprod Health ; 17(1): 181, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33218353

RESUMO

BACKGROUND: Letrozole can significantly decrease the estrogen level, and has been administrated to prevent the incidence of early ovary hyperstimulation syndrome (OHSS). However, the effect of Letrozole on prevention of OHSS reached to controversial conclusions. The present meta-analysis aim to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). METHODS: An exhaustive electronic literature search was conducted on MEDLINE, Google Scholar, CNKI and WANFANG MED ONLINE, from inception until May 2018. We include clinical trials that examined the effect of Letrozole on the prevention of early OHSS. The main outcome measures were the incidence of total early OHSS, mild early OHSS, moderate early OHSS, and severe early OHSS. RESULTS: Eight studies included in the review. Of these, five publications evaluated the effect of Letrozolel on the prevention of total, mild, moderate, and severe OHSS, respectively. The results indicated that there was a significantly decreased incidence of total OHSS with Letrozole compared with control group, and there were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Eight studies reported the incidence of moderate + severe OHSS. We found a significant decrease in incidence of moderate + severe OHSS in high-risk women with Letrozole. CONCLUSIONS: Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually; Letrozole should not be considered as the first-line treatment for prevention of OHSS. Further cohort studies are required to explore the effect of Letrozole on the prevention of OHSS. This study aimed to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). A meta-analysis including 8 studies was conducted. There were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually.

5.
IUBMB Life ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33141516

RESUMO

Our previous study showed that silencing of lncRNA Gm14461 alleviated pain in a murine model of trigeminal neuralgia (TN), but the molecular mechanism remains not fully understood. Evidence indicates that astrocyte activation and autophagy are involved in the development of TN. Herein, this study aimed to elucidate whether the pain-relief effect of Gm14461 silencing in TN involved regulation of astrocyte activation and autophagy. A murine model of TN was induced by chronic constriction injury of the infraorbital nerve surgery. The mechanical withdrawal threshold (MWT) was measured to assess the analgesic effect of Gm14461 silencing. Mouse astrocytes were treated with lipopolysaccharide (LPS) as a cell model. Astrocyte activation was evaluated by glial fibrillary acidic protein (GFAP) immunofluorescence and western blot analysis of GFAP. Autophagy was evaluated by LC3 immunofluorescence and western blot analysis of autophagy-related proteins. The results showed that Gm14461 silencing increased MWT value in TN model mice. Meanwhile, Gm14461 silencing inhibited astrocyte activation and enhanced autophagy in both TN mice and LPS-treated astrocytes. The enhancement of autophagy by Gm14461 silencing involved the activation of the AMPK signaling and the suppression of the Akt/mTOR signaling. Collectively, the analgesic effect of Gm14461 silencing in TN was related to attenuation of astrocyte activation via enhancement of autophagy.

6.
Cell Mol Immunol ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110251

RESUMO

A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.

7.
Front Immunol ; 11: 556526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117342

RESUMO

Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4+ T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naïve CD4+ T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1ß, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1ß, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.

8.
Pest Manag Sci ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128494

RESUMO

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. This study sheds new light on the differences in molecular scaffold from commercialized HPPD inhibitors. RESULTS: The compounds A1-A18 and B1-B27 were synthesized for in vitro and greenhouse experiments. The greenhouse experiment data indicated that compounds B14 and B18 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. In vitro testing indicated that the compounds were HPPD inhibitors. Moreover, molecular simulation results show that the compounds B14, B18, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on crop selectivity results, compounds B14 and B18 were selected for maize studies (injury≤10%), indicating its potential for weed control in maize fields. CONCLUSION: These results showed that the pyrazole-benzofuran structure could be used as possible lead compounds for the development of HPPD inhibitors.

9.
Proc Natl Acad Sci U S A ; 117(38): 23707-23716, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32878999

RESUMO

Trafficking of toll-like receptor 3 (TLR3) from the endoplasmic reticulum (ER) to endolysosomes and its subsequent proteolytic cleavage are required for it to sense viral double-stranded RNA (dsRNA) and trigger antiviral response, yet the underlying mechanisms remain enigmatic. We show that the E3 ubiquitin ligase TRIM3 is mainly located in the Golgi apparatus and transported to the early endosomes upon stimulation with the dsRNA analog poly(I:C). TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831, which is enhanced following poly(I:C) stimulation. The polyubiquitinated TLR3 is recognized and sorted by the ESCRT (endosomal sorting complex required for transport) complexes to endolysosomes. Deficiency of TRIM3 impairs TLR3 trafficking from the Golgi apparatus to endosomes and its subsequent activation. Trim3 -/- cells and mice express lower levels of antiviral genes and show lower levels of inflammatory response following poly(I:C) but not lipopolysaccharide (LPS) stimulation. These findings suggest that TRIM3-mediated polyubiquitination of TLR3 represents a feedback-positive regulatory mechanism for TLR3-mediated innate immune and inflammatory responses.


Assuntos
Proteínas de Transporte/imunologia , Complexos Endossomais de Distribuição Requeridos para Transporte/imunologia , Imunidade Inata/imunologia , Receptor 3 Toll-Like/imunologia , Ubiquitinação/imunologia , Animais , Antivirais/imunologia , Células HEK293 , Humanos , Lisossomos/imunologia , Camundongos , Transporte Proteico/imunologia , RNA Viral/imunologia , Transdução de Sinais/imunologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-32891539

RESUMO

BACKGROUND: The causative pathogen of pediatric osteomyelitis is often unidentified despite culturing attempts. This study evaluated and compared the clinical characteristics, therapeutic approach, and outcomes of osteomyelitis caused by unknown pathogens and identified microorganisms. METHOD: This 17-year retrospective study was conducted at a tertiary hospital in central Taiwan. Medical records of children aged less than 18 years with a diagnosis of osteomyelitis between 2003 and 2019 were reviewed. RESULT: In total, 70 patients (median age = 6.4 years; male = 65.7%) fulfilled the inclusion criteria, of whom 33 (47.1%) were culture negative. Staphylococcus aureus was the main pathogen (67.6% of identified bacteria). The proportion of methicillin-resistant S. aureus (MRSA) was 44% and 54.5% of the MRSA isolates exhibited clindamycin resistance. Compared to children with culture-positive osteomyelitis, those with culture-negative osteomyelitis had a lower rate of concomitant septic arthritis (40.5% vs. 15.2%, p = 0.019) and leukocytosis on presentation (45.9% vs. 21.2%, p = 0.030); they also required fewer surgical interventions (56.8% vs. 24.2%, p = 0.006) and received a shorter course of total antibiotic therapy (49.0 vs. 43.0 days, p = 0.045). In the culture-negative group, the MRSA coverage rate was 18.8% during initial empirical therapy and increased to 59.4% during further adjusted therapy. The overall complication rate was 18.6% and was lower in the culture-negative group (32.4% vs. 3.0%, p = 0.002). CONCLUSION: In areas where community-associated MRSA and clindamycin resistance strains are a concern, empirical glycopeptide-based therapy is suggested in pediatric osteomyelitis, particularly in those with culture-negative infections.

11.
Chin J Nat Med ; 18(9): 677-683, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32928511

RESUMO

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B (1) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the 15N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.

13.
Int J Pharm ; 589: 119869, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32919000

RESUMO

To reduce systemic bleeding risks during anticoagulant treatment, a new concept named "precise anticoagulation" was proposed to localize the effects of anticoagulants via the targeted delivery of prodrugs to the coagulation site. In this study, the fusion protein Annexin V-hirudin 3-ABD (hAvHA) was constructed to achieve the prolonged circulation and targeted delivery of hirudin to coagulation sites. hAvHA was inactive as a prodrug, and it could bind to albumin during circulation. The drug was quickly activated via factor Xa-mediated cleavage once coagulation occurred, and hirudin was efficiently released to exert antithrombin activity in vitro. The hAvHA protein could be activated in mouse blood and exert significant anticoagulation effects. The results of FITC labeling illustrated that hAvHA bound to procoagulant platelets, suggesting the Annexin V modification permits targeted delivery to sites of thrombosis. hAvHA bound to albumin in vitro with an equilibrium dissociation constant of 8 pM, suggesting the ABD modification permitted prolonged circulation in vivo. Moreover, the bleeding time was much shorter in hAvHA-treated mice than in hirudin-treated mice. Therefore, our results suggested that that hAvHA is a potential and promising anticoagulant in vivo.

14.
Chem Commun (Camb) ; 56(79): 11720-11734, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-32960206

RESUMO

Borane clusters represent a unique class of nano-objects not only because of their special coordination and 3D structure but also due to their broad applications ranging from heat resistance coating to cancer therapy agent. Borane cluster-containing polymers (BCCPs) can effectively integrate the merits of both borane clusters and polymers. During the last two decades, with the progress of boron chemistry and the development of advanced polymerization techniques, BCCPs with different architectures and properties have been developed. The introduction of borane clusters into polymeric frameworks not only improves the chemical and thermal stability of traditional polymers but also endows BCCPs with many specific properties, such as photoluminescence, chemical sensing, heat resistance, and boron neutron capture therapy. This feature article gives an overview of the preparation of BCCPs, especially focusing on the design and synthetic methodology. We expect that this review will be helpful to researchers working in the fields of polymer chemistry and materials science.

15.
Zhongguo Zhen Jiu ; 40(9): 953-6, 2020 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-32959590

RESUMO

OBJECTIVE: To compare the clinical effect of lower extremity varicose veins between fire needling bloodletting and operation, and to explore the possible mechanism. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. In the control group,the operation was adopted. The fire needling bloodletting was applied in the observation group, twice a week for 4 weeks. Before and after treatment, the venous clinical severity score (VCSS) and venous disability score (VDS) were recorded, the hemorheological indexes [blood viscosity, plasma viscosity, hematocrit, fibrinogen and erythrocyte sedimentation rate (ESR)], immune inflammatory response indexes[serum C-reactive protein (CRP), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6)], vascular endothelial cell function indexes [the number of circulatingendothelial cell (CEC), plasma endothelin (ET-1) and NO)] and apoptosis indexes (Bcl-2, Bax and Caspase-3) were detected in the two groups. RESULTS: Compared before treatment, the scores of VCSS and VDS, hemorheological indexes, immune inflammatory response indexes and levels of plasma NO after treatment were reduced in the two groups (P<0.05). The level of serum Bax after treatment was reduced in the observation group (P<0.05). The number of CEC and levels of plasma ET-1 after treatment were increased in the two groups (P<0.05). The levels of serum Bcl-2 and Caspase-3 after treatment were increased in the observation group (P<0.05). In the observation group, the scores of VCSS and VDS, hemorheological indexes,immune inflammatory response indexes, vascular endothelial cell function indexes and level of serum Bax after treatment were lower than the control group (P<0.05), and the levels of Bcl-2 and Caspase-3 were higher than the control group (P<0.05). CONCLUSION: Fire needling bloodletting could effectively treat lower extremity varicose veins, and the mechanism may be related to the improvement of hemorheology, downregulation of immune inflammatory response, improvement of vascular endothelial cell function and inhibition of apoptosis.

16.
J Control Release ; 328: 45-58, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32860924

RESUMO

Lanthanum can reduce absorption of phosphate by forming lanthanum phosphate complexes after oral administration of lanthanum carbonate tablets (FOSRENOL®) in patients. Based on the pH-responsive interaction of phosphate and lanthanum ions, the chitosan coated siRNA-loaded lanthanum phosphate nanoparticles (CS/LaP/siRNA NPs) were prepared for improving cancer treatment, in which polysaccharide chitosan was used as the outer shell to control the excessive growth of lanthanum phosphate complexes, and enable intestinal mucoadhesion. The CS/LaP/siEGFR NPs exhibited significant biological activities in human colorectal cancer HT-29 cells by the synergistic effects of siEGFRs and lanthanum ions, such as downregulation of EGFR and upregulation of miR-34a. Furthermore, significant tumor growth inhibition was observed in both transgenic C57BL/6-ApcMinC/Nju cancer mouse model and AOM/DSS chemically induced orthotopic colorectal cancer mouse model after intestinal instillation administration of CS/LaP/siEGFR NPs. Therefore, the lanthanum-based siRNA delivery system would provide a potential and efficient strategy for the treatment of colorectal cancers.

17.
World Neurosurg ; 143: e640-e647, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32791229

RESUMO

BACKGROUND: Chiari malformation type I (CMI) cases are frequently associated with basilar invagination (BI), which complicates the understanding of the pathology of CMI. We specifically evaluated the morphometric and volumetric alterations in the bony structures of CMI patients without BI. METHODS: Fifty adult CMI patients without BI treated at our institution from January 2015 to December 2019 were retrospectively studied. The morphometric and volumetric characteristics of the posterior cranial fossa (PCF) were analyzed using thin-slice computed tomography images. RESULTS: Compared with the controls, the clivus length (P < 0.001), supraoccipital length (P < 0.001), Klaus height index (P < 0.001), axial length (P < 0.001), clivo-axial angle (P < 0.001), tentorial angle (P < 0.05), and bony PCF volume (P < 0.001) of the CMI-only group were significantly smaller, and the distance between the Chamberlain line and the dens axis (P < 0.001), clivus angle (P < 0.001), and basal angle (P < 0.001) of the CMI-only group were significantly larger, while the distance between the McRae line and the dens axis, McRae line, anteroposterior diameter of the PCF, occipital angle, occipital canal angle, and tentorial Twining line angle showed no significant difference between the 2 groups. CONCLUSIONS: Hypoplasia of the clivus and occipital bone were confirmed in CMI patients without BI, thus providing further evidence for the notion that CMI is secondary to the underdevelopment of the PCF.

18.
Protein Cell ; 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772249

RESUMO

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

19.
Ann Palliat Med ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32787377

RESUMO

It is essential for acute ischemic stroke (AIS) patients to receive timely revascularization. However, intravenous thrombolysis (IVT) is not recommended for AIS patients with warfarin associated hypocoagulability. Meanwhile, monotherapy of coagulation factors or vitamin K is unable to reverse anticoagulation of warfarin in emergency. Thus, developing an effective IVT strategy poses a challenging task for these fragile population. Herein, an 82-year-old male, on regular administration with warfarin because of nonvalvular atrial fibrillation (NVAF), suffered from AIS and had an elevated international normalized ratio value of 1.72 and prolonged prothrombin time of 18.2 s at stroke onset. For normalizing INR, combination of 4 factor prothrombin complex concentrate, fresh frozen plasma and vitamin K1 were administrated. Finally, the patient successfully received recombinant tissue plasminogen activator (rt-PA), with an obviously neurological improvement. This case shows a feasible role of IVT therapy with rt-PA after reversal of coagulation regarding AIS patients with warfarin-related hypocoagulability.

20.
Cell Mol Life Sci ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32851475

RESUMO

Proteasome inhibitors, such as bortezomib and carfilzomib, have shown efficacy in anti-cancer therapy in hematological diseases but not in solid cancers. Here, we found that liposarcomas (LPS) are susceptible to proteasome inhibition, and identified drugs that synergize with carfilzomib, such as selinexor, an inhibitor of XPO1-mediated nuclear export. Through quantitative nuclear protein profiling and phospho-kinase arrays, we identified potential mode of actions of this combination, including interference with ribosome biogenesis and inhibition of pro-survival kinase PRAS40. Furthermore, by assessing global protein levels changes, FADS2, a key enzyme regulating fatty acids synthesis, was found down-regulated after proteasome inhibition. Interestingly, SC26196, an inhibitor of FADS2, synergized with carfilzomib. Finally, to identify further combinational options, we performed high-throughput drug screening and uncovered novel drug interactions with carfilzomib. For instance, cyclosporin A, a known immunosuppressive agent, enhanced carfilzomib's efficacy in vitro and in vivo. Altogether, these results demonstrate that carfilzomib and its combinations could be repurposed for LPS clinical management.

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