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1.
Front Immunol ; 12: 748573, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759927

RESUMO

The cytokine storm is a marker of severity of various diseases and increased mortality. The altered metabolic profile and energy generation of immune cells affects their activation, exacerbating the cytokine storm. Currently, the emerging field of immunometabolism has highlighted the importance of specific metabolic pathways in immune regulation. The glycolytic enzyme pyruvate kinase M2 (PKM2) is a key regulator of immunometabolism and bridges metabolic and inflammatory dysfunction. This enzyme changes its conformation thus walks in different fields including metabolism and inflammation and associates with various transcription factors. This review summarizes the vital role of PKM2 in mediating immunometabolic reprogramming and its role in inducing cytokine storm, with a focus on providing references for further understanding of its pathological functions and for proposing new targets for the treatment of related diseases.

2.
MedComm (2020) ; 2(2): 221-235, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34766143

RESUMO

ATP-binding cassette (ABC) transporters superfamily mediates multidrug resistance in cancer by extruding structurally distinct chemotherapeutic agents, causing failure in chemotherapy. Among the 49 ABC transporters, multidrug resistance protein 7 (MRP7 or ABCC10) is relatively new and has been identified as the efflux pump of multiple anticancer agents including Vinca alkaloids and taxanes. Herein, we construct and validate a homology model for human MRP7 based on the cryo-EM structures of MRP1. Structure-function relationship of MRP7 was obtained from molecular dynamics simulations and docking studies and was in accordance with previous studies of ABC transporters. The motion patterns correlated with efflux mechanism were discussed. Additionally, predicted substrate- and modulator-binding sites of MRP7 were described for the first time, which provided rational insights in understanding the drug binding and functional regulation in MRP7. Our findings will benefit the high-throughput virtual screening and development of MRP7 modulators in the future.

3.
J Am Chem Soc ; 143(46): 19606-19613, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34766768

RESUMO

Most proteins perform their functions in cells. How the cellular environment modulates protein interactions is an important question. In this work, electrostatic interactions between protein charges were studied using in-cell nuclear magnetic resonance (NMR) spectroscopy. A total of eight charge pairs were introduced in protein GB3. Compared to the charge pair electrostatic interactions in a buffer, five charge pairs in cells displayed no apparent changes whereas three pairs had the interactions weakened by more than 70%. Further investigation suggests that the transfer free energy is responsible for the electrostatic interaction modulation. Both the transfer free energy of the folded state and that of the unfolded state can contribute to the cellular environmental effect on protein electrostatics, although the latter is generally larger (more negative) than the former. Our work highlights the importance of direct in-cell studies of protein interactions and thus protein function.

4.
Math Biosci Eng ; 18(6): 8392-8414, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34814305

RESUMO

In this paper, we develop two stochastic mussel-algae models: one is autonomous and the other is periodic. For the autonomous model, we provide sufficient conditions for the extinction, nonpersistent in the mean and weak persistence, and demonstrate that the model possesses a unique ergodic stationary distribution by constructing some suitable Lyapunov functions. For the periodic model, we testify that it has a periodic solution. The theoretical findings are also applied to practice to dissect the effects of environmental perturbations on the growth of mussel.

5.
Math Biosci Eng ; 18(6): 9094-9120, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34814337

RESUMO

In this manuscript, a novel predator-prey system combining prey refuge with fuzzy parameters is formulated. Sufficient conditions for the existence and stability of biological equilibria are derived. The existence of bionomic equilibria is discussed under fuzzy biological parameters. The optimal harvesting policy, by Pontryagin's maximal principle, is also investigated under imprecise inflation and discount in fuzzy environment. Meticulous numerical simulations are performed to validate our theoretical analysis in detail.

6.
Drug Discov Today ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34678489

RESUMO

Human herpes simplex viruses (HSVs) belong to the Herpesviridae family. At present, no vaccine or curative treatment is available for the prevention of HSV infections. Here, we review the cell surface receptors that are recognized by HSV's glycoprotein B, glycoprotein C, glycoprotein D, and the glycoprotein H - glycoprotein L complex to facilitate entry into host cells. These receptors include heparan sulfate (HS), herpesvirus entry mediator (HVEM), and nectin-1/-2, 3-O-sulfated heparan sulfate (3-OS HS).

7.
Vaccines (Basel) ; 9(10)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34696263

RESUMO

Capsular type A and D strains of Pasteurella multocida are the main epidemic serogroups in pigs in China. In this study, we preliminarily evaluated the immune protective efficacy of the two traditional vaccines, an inactivated C44-1 aluminum-hydroxide-gel-adjuvanted (Alh-C44-1) vaccine and a live EO630 vaccine, against currently circulating strains of P. multocida in a mouse model. Mice immunized twice with conventional vaccines generated higher antibody titers, and significantly higher levels of IgG were observed in the mice inoculated with the inactivated Alh-C44-1 vaccine on day 35 (p < 0.05) than those with the live EO630 vaccine. The mice immune protection test showed that the vaccination groups had a 57% or 71% protection effect against the serogroup B strain, but had no protective effect against epidemic strains. In conclusion, our study found that the widely used traditional P. multocida vaccines in China provide good protection against homologous strains, but could not provide cross-protection against heterologous strains in a mouse model.

8.
Adv Sci (Weinh) ; : e2102653, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716691

RESUMO

The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid-liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ-binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ-driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ-driven oncogenic transcriptional program.

9.
World J Clin Cases ; 9(27): 8114-8119, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34621869

RESUMO

BACKGROUND: Empyema is a severe complication following pneumonectomy that is associated with high morbidity and mortality rates. Although there are a wide variety of treatment options, successful management remains challenging when this condition is combined with a large cavity in very thin patients who had previously undergone a posterolateral thoracotomy. CASE SUMMARY: We reported the case of a thin, 63-year-old man with a progressive pulmonary cyst who underwent left pneumonectomy via posterolateral thoracotomy 23 years ago. After an initially uneventful postoperative course, he was readmitted with empyema and a large cavity 21 years after surgery. He was successfully treated with limited thoracoplasty, followed by free vastus lateralis musculocutaneous flap transposition. CONCLUSION: This case highlights that the treatment mode of limited thoracoplasty and free vastus lateralis musculocutaneous flap transposition is safe and effective for the management of postpneumonectomy empyema with a large cavity in thin patients who had previously undergone a posterolateral thoracotomy.

10.
Mol Ther ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34601133

RESUMO

Hepatocellular carcinoma (HCC) is frequently characterized by metabolic and immune remodeling in the tumor microenvironment. We previously discovered that liver-specific deletion of fructose-1, 6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme ubiquitously suppressed in HCC tissues, promotes liver tumorigenesis and induces metabolic and immune perturbations closely resembling human HCC. However, the underlying mechanisms remain incompletely understood. Here, we reported that FBP1-deficient livers exhibit diminished amounts of natural killer (NK) cells and accelerated tumorigenesis. Using the diethylnitrosamine-induced HCC mouse model, we analyzed potential changes in the immune cell populations purified from control and FBP1-depleted livers and found that NK cells were strongly suppressed. Mechanistically, FBP1 attenuation in hepatocytes derepresses an zeste homolog 2 (EZH2)-dependent transcriptional program to inhibit PKLR expression. This leads to reduced levels of PKLR cargo proteins sorted into hepatocyte-derived extracellular vesicles (EVs), dampened activity of EV-targeted NK cells, and accelerated liver tumorigenesis. Our study demonstrated that hepatic FBP1 depletion promotes HCC-associated immune remodeling, partly through the transfer of hepatocyte-secreted, PKLR-attenuated EVs to NK cells.

11.
STAR Protoc ; 2(4): 100871, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34661172

RESUMO

Vaccinia virus is a large double-stranded DNA virus that is widely used to express foreign genes from different origins. We generated recombinant vaccinia virus that expresses a viral inhibitor to examine its effect on virus-induced necroptosis. We provide a detailed protocol to describe the generation of recombinant vaccinia virus, validation of protein expression, and determination of necroptosis using live cell imaging. This approach can be adapted to examine the effect of other cell death regulators on virus-induced cell death. For complete details on the use and execution of this protocol, please refer to Liu et al. (2021).

12.
Opt Express ; 29(18): 28277-28286, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34614962

RESUMO

Metamaterials of metal-insulator-metal structures represent effective ways in manipulating light absorbance for photodetection, sensing, and energy harvesting etc. Most of the time, specular reflection has been used in characterizing resonances of metamaterials without considering diffuse scattering from their periodic subwavelength units. In this paper, we investigate diffuse reflection in metasurfaces made of periodic metallic disks in the mid-infrared region. Integrating sphere-based spectral measurements indicate that diffuse reflection is dominated by grating diffractions, which cause diffuse scattering in a spectral region with wavelengths less than that of the first order Rayleigh anomaly. The diffuse reflection is greatly enhanced by the metasurface resonance and exhibits a general increase towards shorter wavelengths, which not only causes a significant difference in evaluating the metamaterial resonant absorption efficiency but also a small blue-shift of the resonance frequency. These findings are helpful for designing and analyzing metamaterial resonant properties when diffuse scattering is taken into account.

13.
J Appl Math Comput ; : 1-20, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34539296

RESUMO

Two types of stochastic epidemic models are formulated, in which both infectivity in the latent period and household quarantine on the susceptible are incorporated. With the help of Lyapunov functions and Has'minskii's theory, we derive that, for the nonautonomous periodic version with white noises, it owns a positive periodic solution. For the other version with white and telephone noises, we construct stochastic Lyapunov function with regime switching to present easily verifiable sufficient criteria for the existence of ergodic stationary distribution. Also, we introduce a series of numerical simulations to support our analytical findings. At last, a brief discussion of our theoretical results shows that the stochastic perturbations and household quarantine measures can significantly affect both periodicity and stationary distribution.

14.
Eur J Pharmacol ; 911: 174522, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34560076

RESUMO

Cynaroside is the primary flavonoid component of honeysuckle which has been widely used as Chinese traditional medicine given its anti-inflammation properties. Overactive systemic inflammatory response and multi-organ injury are the leading causes of life-threatening sepsis. Regulation of macrophage polarization balance may act as a promising strategy for its treatment. In the present study, we aimed to investigate whether cynaroside exerted protective effects against sepsis and its potential mechanism. Building upon a sepsis mouse model, we observed cynaroside alleviated serum levels of inflammatory factors including IL-1ß and TNF-α at 5 and 10 mg/kg. The pathological injury of heart, kidney and lung was remarkedly attenuated as the levels of blood urea nitrogen, creatinine, creatine kinase-MB and lactate dehydrogenase were reduced nearly 2.8-, 2.7-, 2.4-, and 2.5-fold as compared with the sepsis mice, respectively. We further demonstrated cynaroside suppressed the biomarker of pro-inflammatory macrophage M1 phenotype (iNOS+) and promotes the anti-inflammatory M2 polarization (CD206+) in the injury organs of septic mice. Mechanistic research verified cynaroside inhibited LPS-induced polarization of macrophage into M1 phenotype, which can be highly blocked by Nrf2 inhibitor. Expectedly, Nrf2 and its downstream (Heme oxygenase-1 (HO-1)) was upregulated in injury organs after treating with cynaroside, indicating the involvement of Nrf2 signaling. Taken together, the data claims cynaroside ameliorated systematic inflammation and multi-organ injury dependent on Nrf2/HO-1 pathway in septic mice.

15.
J Virol Methods ; 298: 114298, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34560110

RESUMO

Enterovirus A (EV-A) species are the main agents responsible for hand, foot, and mouth disease (HFMD), a serious public health concern. Lack of appropriate reagents prevents the mechanistic study of these virus infections. 2C protein, a non-structural protein of Enterovirus, is crucial for viral replication and antiviral immunity. Here, preparation and testing of a monoclonal antibody by immunizing mice with Coxsackievirus A10 protein 2C (CVA10-2C) was reported. This antibody could identify most EV-A types, both conventional and unconventional groups. We also mapped the antibody epitope SLATGIIARA, which is highly conserved in EV-A species and located in the ATPase domain. Some key amino acids include G140, I141, I142, and R144. In conclusion, we generated a recombinant monoclonal antibody against multiple EVA types and confirmed its performance, which may facilitate the future study of Enterovirus A infection and many potential applications, such as the diagnosis of pathogen or the development of antiviral therapies.

16.
Front Bioeng Biotechnol ; 9: 684335, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350160

RESUMO

Bone defects are difficult to repair and reconstruct as bone regeneration remains technically challenging, with exogenous factors required to accelerate this process. Biodegradable synthetic scaffolds are promising materials for stimulating bone tissue repair. In this study, we investigated whether a bilayer membrane that includes mineralized collagen (MC) and chitosan (CS) delivering berberine (BER)-a typical Chinese herbal monomer-could promote bone healing in a rat model. An MC/CS cast film was coated with polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) electrospun nanofibers loaded with BER, yielding the BER@PCL/PVP-MC/CS bilayer membrane. The 3-dimensional structure had nanofibers of uniform diameter and showed good hydrophilicity; the bilayer membrane showed favorable mechanical properties. BER@PCL/PVP-MC/CS enhanced the proliferation and attachment of MC3T3-E1 cells in vitro and induced bone regeneration when implanted into a rat femoral bone defect. These findings provide evidence that BER@PCL/PVP-MC/CS has clinical potential for effective bone repair.

17.
Front Pharmacol ; 12: 720726, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366872

RESUMO

Antibiotic resistance or microbial drug resistance is emerging as a serious threat to human healthcare globally, and the multidrug-resistant (MDR) strains are imposing major hurdles to the progression of drug discovery programs. Newer antibiotic-resistance mechanisms in microbes contribute to the inefficacy of the existing drugs along with the prolonged illness and escalating expenditures. The injudicious usage of the conventional and commonly available antibiotics in human health, hygiene, veterinary and agricultural practices is proving to be a major driver for evolution, persistence and spread of antibiotic-resistance at a frightening rate. The drying pipeline of new and potent antibiotics is adding to the severity. Therefore, novel and effective new drugs and innovative therapies to treat MDR infections are urgently needed. Apart from the different natural and synthetic drugs being tested, plant secondary metabolites or phytochemicals are proving efficient in combating the drug-resistant strains. Various phytochemicals from classes including alkaloids, phenols, coumarins, terpenes have been successfully demonstrated their inhibitory potential against the drug-resistant pathogens. Several phytochemicals have proved effective against the molecular determinants responsible for attaining the drug resistance in pathogens like membrane proteins, biofilms, efflux pumps and bacterial cell communications. However, translational success rate needs to be improved, but the trends are encouraging. This review highlights current knowledge and developments associated challenges and future prospects for the successful application of phytochemicals in combating antibiotic resistance and the resistant microbial pathogens.

18.
Mitochondrial DNA B Resour ; 6(7): 2017-2018, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377786

RESUMO

Ruellia simplex C.Wright is a perennial plant of the Acanthaceae, which has significant ornamental value. Because of its strong adaptability, it is widely planted in Chinese rural areas. Based on sequencing data from Illumina, the first complete chloroplast (cp) genome of Ruellia simplex C.Wright is reported in this paper. This cp genome was 143,016bp in length, including a large single-copy region (LSC) of 91,857bp, a small single-copy (SSC) of 17,591bp and two inverted repeat regions (IRs) of 16,784bp. It contained 128 genes, 35 transfer RNA genes, 8 ribosomal RNA genes, with an overall GC content of 38.41%. Additionally, the phylogenetic analysis showed that Ruellia simplex is closely related to Strobilanthes cusia (NC_037485), Strobilanthes bantonensis (MT576695) and Echinacanthus attenuatus (NC_039762). The results of this study provide valuable information for the continued study of its species evolution, genetic engineering and germplasm resource utilization.

19.
Exp Cell Res ; 405(2): 112728, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34246653

RESUMO

ATP-binding cassette (ABC) transporter C10 (ABCC10), also named multidrug resistance protein 7 (MRP7), is a member of ABC transporter superfamily and has been revealed to transport a wide range of chemotherapeutic agents including taxanes, epothilone B, Vinca alkaloids, and anthracyclines. In our previous study, a 5-cyano-6-phenylpyrimidin derivative CP55 was synthesized and found significantly reversal effect of multidrug resistance (MDR) mediated by ABCB1. In this study, we found CP55 also efficiently reversed MDR mediated by ABCC10. Our in vitro study showed that co-treatment with CP55 significantly increased the efficacy of ABCC10-substrate anticancer drugs in MDR cells overexpressing ABCC10. Furthermore, we showed that treatment with CP55 increased the intracellular accumulation of [3H]-labeled anticancer drugs and in-turn decreasing drug efflux by inhibiting the transport activity, without altering ABCC10 protein ex-pression level or cellular localization. Potential CP55-ABCC10 interactions were predicted via docking analysis using human ABCC10 homology model and obtained high docking score. Therefore, CP55 represents a promising therapeutic agent in the combinational treatment of chemo-resistant cancer related to ABCC10.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/fisiologia , Humanos , Proteínas de Neoplasias/metabolismo , Sensibilidade e Especificidade
20.
Math Biosci Eng ; 18(4): 3160-3179, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-34198379

RESUMO

To investigate the roles of both coupling noises and distributed delays with strong kernels, a novel delayed stochastic two-species facultative mutualism model is established, in where the strong kernels indicate that the maximum influence on the growth rate response at some time is due to population densities at the previous time, and the saturation effect is also incorporated because the facultative capacity of each species is finite and their interspecific mutualism should be upper bounded in real life. We first transfer the two-species stochastic model with strong kernels into an equivalent six-dimensional model through a linear chain technique. Later, sufficient conditions for the extinction exponentially, persistence in the mean, permanent in time average and stationary distribution are respectively obtained. Finally, numerical simulations are supplied to support our theoretical results. Our analytical results show that the coupling noise intensities play an important role in the long-time behaviors while the strong kernels are independent of the above asymptotic properties.


Assuntos
Simbiose , Densidade Demográfica , Processos Estocásticos
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