Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 545
Filtrar
1.
Mol Nutr Food Res ; : e2100157, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061446

RESUMO

SCOPE: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aimed to investigate whether betaine affects muscle loss by improving protein synthesis. METHODS AND RESULTS: Male C57BL/6J mice were raised from aged 12 mon or 15 mon. Mice were fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group (Con) or betaine intervention group (Bet) respectively. Betaine supplementation to mice demonstrated better body composition, grip strength and motor function. Muscle morphology, upregulated expression of myogenic regulate factors (MRFs), and elevated myosin heavy chain (MyHC) also improved in Bet group. Betaine promoted muscle protein synthesis (MPS) via tethering mTORC1 on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned were time-dependent (P < 0.05). UPLC results found betaine increased S-adenosyl-L-methionine (SAM) via methionine cycle. SAM sensor - Samtor - overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibited the mTORC1 signaling. Addition of betaine attenuated this inhibition by increasing SAM level and then disrupting interaction of Samtor complex. CONCLUSIONS: These observations indicated betaine could promisingly promote protein synthesis to delay age-related muscle loss. This article is protected by copyright. All rights reserved.

3.
Kaohsiung J Med Sci ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33973356

RESUMO

Alcoholic fatty liver disease (AFLD) is the most common liver disease and can progress to fatal liver cirrhosis and carcinoma, affecting millions of patients worldwide. The functions of astragaloside on the cardiovascular system have been elucidated. However, its role in AFLD is unclear. Ethanol-treated AML-12 cells were used as a cell model of alcoholic fatty liver. Real-time quantitative reverse transcription-PCR and Western blotting detected genes and proteins expressions. Reactive oxygen species (ROS), triglyceride, total cholesterol, low-density lipoprotein, albumin, ferritin, bilirubin, superoxide dismutase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were examined using commercial kits. Lipid accumulation was assessed by Oil red O staining. MTT and flow cytometry measured cell viability and apoptosis. JC-1 was used to analyze mitochondrial membrane potential. A rat model of AFLD was established by treating rats with ethanol. Astragaloside suppressed ethanol-induced lipid accumulation, oxidative stress, and the production of AST and ALT in AML-12 cells. Ethanol induced TNF-α and reduced IL-10 expression, which were reversed by astragaloside. Ethanol promoted Bax expression and cytochrome C release and inhibited Bcl-2 and ATP expression. Astragaloside hampered these apoptosis effects in AML-12 cells. Impaired mitochondrial membrane potential was recovered by astragaloside. However, all these astragaloside-mediated beneficial effects were abolished by the ROS inducer pyocyanin. Ethanol-induced activation of NF-κB signaling was suppressed by astragaloside in vitro and in vivo, suggesting that astragaloside inhibited oxidative stress by suppressing the activation of NF-κB signaling, thus improving liver function and alleviating AFLD in rats. Our study elucidates the pharmacological mechanism of astragaloside and provides potential therapeutic strategies for AFLD.

4.
Biosaf Health ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34027383

RESUMO

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a recently discovered coronavirus that causes severe and acute diarrhea and rapid weight loss in piglets. SADS-CoV was reported to be capable of infecting cell lines derived from diverse species, including bats, mice, hamsters, rats, chickens, pigs, nonhuman primates, and humans, implying its high risk of cross-species infection. However, its receptor is still unknown. In this study, the receptor-binding domain of the SADS-CoV spike (S) protein was purified and then subjected to affinity purification (AP)-coupled mass spectrometry (MS)-based proteomic analysis to identify the interactors of the SADS-CoV S protein. Forty-three host proteins were identified, and a Gene Ontology analysis indicated that these interactors can be grouped into categories such as "cell-cell adhesion", "translation" "viral transcription", suggesting that these processes may participate in the SADS-CoV life cycles. RNA interference-based screening of these interactors indicated that PPIB and vimentin can affect SADS-CoV replication. Our study provides an overarching view into the host interactome of the SADS-CoV S protein and highlights potential targets for the development of therapeutics against SADS-CoV.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34024736

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury (IRI) represents a crucial challenge in liver transplantation. Fisetin has anti-inflammatory, anti-aging and anti-oxidative properties. This study aimed to examine whether fisetin mitigates hepatic IRI and examine its underlying mechanisms. METHODS: Sham or warm hepatic I/R operated mice were pretreated with fisetin (5, 10 or 20 mg/kg). Hepatic histological assessments, TUNEL assays and serum aminotransferase measurements were performed. An in vitro hypoxia/reoxygenation (H/R) model using RAW264.7 macrophages pretreated with fisetin (2.5, 5 or 10 µmol/L) was also used. Serum and cell supernatant concentrations of interleukin-1ß (IL-1ß), IL-18 and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Protein levels of p-GSK3ß, p-AMPK and NLR family pyrin domain-containing 3 (NLRP3)-associated proteins were detected by Western blotting. RESULTS: Compared with the I/R group, fisetin pretreatment reduced pathological liver damage, serum aminotransferase levels, serum concentrations of IL-1ß, IL-18 and TNF-α in the murine IRI model. Fisetin also reduced the expression of NLRP3 inflammasome-associated proteins (NLRP3, cleaved caspase-1, IL-1ß and IL-18) in I/R-operated liver. The experiments in vitro showed that fisetin decreased the release of IL-1ß, IL-18 and TNF-α, and reduced the expression of NLRP3 inflammasome-associated proteins in H/R-treated RAW264.7 cells. Moreover, fisetin increased the expressions of p-GSK3ß and p-AMPK in both models, indicating that its anti-inflammatory effects were dependent on GSK3ß/AMPK signaling. The anti-inflammatory effects of fisetin were partially inhibited by the AMPK specific inhibitor compound C. CONCLUSIONS: Fisetin showed protective effects against hepatic IRI, countering inflammatory responses through mediating the GSK3ß/AMPK/NLRP3 inflammasome pathway.

6.
J Colloid Interface Sci ; 600: 820-827, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34052532

RESUMO

We report CoFe2O4 and carbon nanotubes hybrid aerogels as a novel anode material for potassium ion batteries (KIBs). The synthetic route take the advantage of marine biobased materials as the precursor and facilely produce large-scale production of hybrid CoFe2O4 and carbon nanotubes aerogels as the advanced anode. The hybrid aerogels deliver a remarkable capacity of 180 mAh g-1 with high stability over 200 cycles at a current density of 0.1 A g-1. The high rate charge/discharge reveals a relatively high capacity of 83 mAh g-1 even at the current density of 1.0 A g-1. In-situ XRD investigations reveal the phase evolution during charge/discharge, demonstrating the high stability of hybrid aerogels for the potassium intercalation/extraction. The high specific surface area and large numbers of mesopores with more active sites can benefit the effective transmission of electrons and K ions, leading to an improved specific capacity and cycle stability.

7.
Int Immunopharmacol ; 96: 107604, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839577

RESUMO

Hepatic ischemia/reperfusion injury (IRI) is an inevitable pathological process in liver resection, shock and transplantation. However, the internal mechanism of hepatic IRI, including inflammatory transduction of multiple signaling pathways, is not fully understood. In the present study, we identified pleckstrin homology-like domain family member 1 (PHLDA1), suppressed by microRNA (miR)-194, as a critical intersection of dual inflammatory signals in hepatic IRI. PHLDA1 was upregulated in hepatic IRI with a concomitant downregulation of miR-194. Overexpression of miR-194 diminished PHLDA1 and inhibitors of the nuclear factor kappa-B kinase (IKK) pathway, thus leading to remission of hepatic pathological injury, apoptosis and release of cytokines. Further enrichment of PHLDA1 reversed the function of miR-194 both in vivo and in vitro. For an in-depth query, we verified PHLDA1 as a direct target of miR-194. Notably, inflammatory signal transduction of PHLDA1 was induced by activating TNF receptor-associated factor 6 (TRAF6), sequentially initiating IKK and mitogen-activated protein kinase (MAPK), both of which aggravate stress and inflammation in hepatic IRI. In conclusion, the miR-194/PHLDA1 axis was a key upstream regulator of IKK and MAPK in hepatic IRI. Targeting PHLDA1 might be a potential strategy for hepatic IRI therapy.

8.
Methods Mol Biol ; 2302: 311-334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33877635

RESUMO

Over the past decade, concepts of network theory in combination with dynamical information from conformational ensembles have been widely applied to gain insights in understanding allosteric regulation in biomolecules. In this chapter, we introduce the basic theories and protocols used in protein dynamics network analysis through a series of interactive python Jupyter notebook scripts. While various network analysis methods exist in the literature, here we focus on the two popular methods based on correlated atomic motions and pairwise interaction energies. While the tutorial is based on a small prototypic protein, the workflow and protocol introduced here are optimized to handle large membrane proteins.

9.
Chem Commun (Camb) ; 57(31): 3805-3808, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876127

RESUMO

We developed a new method for protein droplet visualization by means of a droplet probe (DroProbe) based on an aggregation-induced emission (AIE) fluorogen. A simple method for viscosity comparison of the protein condensed phase based on the lifetime of the DroProbe was also developed.

11.
J Adv Res ; 29: 83-94, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33842007

RESUMO

Introduction: Inflammation is a key factor in myocardial ischemia/reperfusion (MI/R) injury. Targeting leucocyte-mediated inflammation is an important strategy for MI/R therapy. Iminostilbene (ISB), a simple dibenzoazepine small molecule compound, has a strong anti-neurodegenerative effect. However, no study has shown the cardioprotective effect of ISB. Objectives: This study aimed to investigate the role of ISB against MI/R injury and identify its molecular target. Methods: To verify the cardiac protection of ISB in vivo and in vitro, we performed rat MI/R surgery and subjected inflammatory modeling of macrophages. In terms of molecular mechanisms, we designed and synthesized a small molecular probe of ISB and employed it on the click chemistry-activity-based protein profiling technique to fish for ISB targets in macrophages. To identify the target, we applied the competitive inhibition assay, surface-plasmon resonance (SPR), cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assay. Results: In vivo, ISB showed robust anti-myocardial injury activity by improving cardiac function, reducing myocardial infarction, and inhibiting macrophage-mediated inflammation. In vitro, ISB strongly inhibited the transcription and the expression levels of inflammatory cytokines in macrophages. The pyruvate kinase isozyme type M2 (PKM2) was identified as the potential target of ISB through proteomic analysis and the competitive assay was performed for specific binding verification. Further thermodynamic and kinetic experiments showed that ISB was bound to PKM2 in a dose-dependent manner. Moreover, in terms of the biological function of ISB on PKM2, ISB reduced the expression of PKM2, thereby reducing the expression of HIF1α and the phosphorylation of STAT3. Conclusion: This study for the first time demonstrated that ISB targeted PKM2 to reduce macrophage inflammation thereby significantly alleviating MI/R injury.

12.
Biomed Res Int ; 2021: 6653387, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33884267

RESUMO

Background: As a newly discovered regulatory RNA, circular RNA (circRNA) has become a hot spot in many tumor pieces of research. In recent years, it has been discovered that circRNAs have multiple biological effects in different stages of cancer. However, the expression pattern and mechanism of circFAT1(e2) in non-small-cell lung cancer (NSCLC) are still unclear. Methods: The expressions of circFAT1(e2) in NSCLC tissues and cell lines were studied. Functionally, CCK-8 and transwell experiments were performed in A549 and H1299. In addition, we also performed a dual-luciferase report analysis to clarify the mechanism of action of circFAT1(e2). Results: circFAT1(e2) was significantly upregulated in NSCLC tissues and cell lines. circFAT1(e2) gene knockdown could significantly inhibit the proliferation, migration, and invasion of NSCLC cells. Loss of function testing found that circFAT1(e2) functioned as an oncogene in NSCLC cells. In addition, circFAT1(e2) acted as a ceRNA to spongy miR-30e-5p, which led to the increase in USP22 and promoted cell growth. Conclusions: The circFAT1(e2)-miR-30e-5p-USP22 axis is a crucial part of the progression of NSCLC. This study suggests that circFAT1(e2) may be an important potential of prognostic prediction and treatment targets for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Circular/metabolismo , Ubiquitina Tiolesterase/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/metabolismo , Metástase Neoplásica , RNA Circular/genética , Ubiquitina Tiolesterase/metabolismo
13.
Biomater Sci ; 9(11): 4066-4075, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33908452

RESUMO

Disseminated tumor cells in bleeding and residual tumor cells in the resection tumor site are the primary factors that result in tumor recurrence after surgery. Safe and efficient local implantation of the drug depot system into the resection cavity to inhibit tumor recurrence would be of great benefit to reduce the mortality of postoperative patients. Here, a sandwich-like doxorubicin-triptolide-loaded fiber/(chitosan/gelatin) sponge, DTF/CGS, is fabricated, combining hemostatic, antibacterial, and chemotherapeutic capability. The CGS obtained via freeze-drying can efficiently prevent bleeding; meanwhile, the metastatic residual tumor cells are stuck with the clotted absorbed blood. Subsequently, dual drugs released from the electrospun fiber can further kill the stuck tumor cells in CGS and the disseminated tumor cells to significantly inhibit the tumor recurrence. This antitumor recurrence strategy by immediately implanting a multifunctional hybrid sponge for in situ postoperative management may possess great potential for preventing tumor recurrence.


Assuntos
Quitosana , Hemostáticos , Doxorrubicina/uso terapêutico , Gelatina , Humanos , Recidiva Local de Neoplasia/prevenção & controle
14.
J Phys Chem B ; 125(10): 2771-2780, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33662212

RESUMO

Cell-surface polysaccharides are essential to many aspects of physiology, serving as a highly conserved evolutionary feature of life and as an important part of the innate immune system in mammals. Here, as simplified biophysical models of these sugar coatings, we present results of molecular dynamics simulations of hyaluronic acid and heparin brushes that show important effects of ion pairing, water dielectric decrease, and coion exclusion. As in prior studies of macromolecular crowding under physiologically relevant salt concentrations, our results show equilibria with electroneutrality attained through screening and pairing of brush anionic charges by monovalent cations at the atomistic detail. Most surprising is the reversal of the Donnan potential obtained from both nonpolarizable and Drude polarizable force fields, in contrast to what would be expected based on electrostatic Boltzmann partitioning alone. Water dielectric decrement within the brush domain is also associated with Born hydration-driven cation exclusion from the brush. We observe that the primary partition energy attracting cations to attain brush electroneutrality is the ion pairing or salt-bridge energy. Potassium and sodium pairings to glycosaminoglycan carboxylates and sulfates show similar abundance of contact-pairing and solvent-separated pairing. We conclude that in these crowded macromolecular brushes, ion-pairing, Born-hydration, and electrostatic potential energies all contribute to attain electroneutrality and should therefore contribute in mean-field models to accurately represent brush electrostatics.


Assuntos
Glicosaminoglicanos , Simulação de Dinâmica Molecular , Solventes , Eletricidade Estática , Água
15.
J Environ Manage ; 287: 112290, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33714734

RESUMO

Over recent years, concerns about the need to reduce energy intensity have intensified due to the increasing volume of greenhouse gas emissions that has amplified problems related to global climate change and environmental pollution. At the same time, foreign direct investment (FDI) has been found to have a prominent effect on energy intensity. This study empirically examines the relationship between sectoral FDI inflows and energy intensity by investigating the possibility of a threshold effect of research and development (R&D) technological absorptive capacity. Our sample covers 34 OECD countries over 1987-2013, with FDI and R&D data disaggregated at three sectoral levels (primary, secondary and tertiary sectors), an analysis that is absent in existing literature. We uncover a significant R&D input threshold in the relationship between FDI inflows to non-primary sectors and energy intensity. FDI inflows to non-primary sectors increase the level of energy intensity when the level of sectoral R&D is below the threshold, but such effect decreases when the sectoral R&D level is above the threshold point. Important implications flow from our findings with respect to the type of FDI and the level of indigenous R&D to be encouraged (or discouraged) by policymakers to effectively reduce energy intensity.


Assuntos
Desenvolvimento Econômico , Organização para a Cooperação e Desenvolvimento Econômico , Dióxido de Carbono , Investimentos em Saúde , Pesquisa
16.
Virol Sin ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616893

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease with a high mortality of ~ 35%. The lack of approved treatments for MERS-CoV infection underscores the need for a user-friendly system for rapid drug screening. In this study, we constructed a MERS-CoV replicon containing the Renilla luciferase (Rluc) reporter gene and a stable luciferase replicon-carrying cell line. Using this cell line, we showed that MERS-CoV replication was inhibited by combined application of lopinavir and ritonavir, indicating that this cell line can be used to screen inhibitors of MERS-CoV replication. Importantly, the MERS-replicon cell line can be used for high-throughput screening of antiviral drugs without the need for live virus handling, providing an effective and safe tool for the discovery of antiviral drugs against MERS-CoV.

17.
Int J Psychophysiol ; 164: 17-22, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33592232

RESUMO

BACKGROUND: Respiratory sinus arrhythmia (RSA) has been understood as a physiological marker of emotional regulatory capacity. To date, little is known about the potential psychophysiological contributions to which influence the family functioning on young adult's internet addiction (IA) symptoms. The aim of this research was to examine the moderating role of resting RSA and its link between family functioning and IA symptoms. METHOD: One-hundred and nine participants (69 men) aged between 17 and 21 years old completed questionnaires on family functioning and IA symptoms. Data pertaining to RSA was collected during a resting period in the laboratory. RESULTS: Resting RSA moderated the association between family functioning and IA symptoms. Specifically, poorer family functioning was related to higher levels of IA symptoms particularly for participants with low resting RSA. When the participants' resting RSA was high, family functioning showed no significant relation with IA symptoms. CONCLUSION: Our findings indicated that lower resting RSA may place young adults at greater risk for IA symptoms. This occurs when exposed to poorer family functioning. Furthermore, high resting RSA may serve as a protective factor that alleviates the detrimental influences of poor family functioning on IA symptoms. These findings highlight that contemporaneous consideration is needed for both contextual and physiological factors. This can help to advance persons understanding of internet addictive behaviors in young adults.

18.
Sci Total Environ ; 772: 144957, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578161

RESUMO

Short-chain chlorinated paraffins (SCCPs) could disrupt fatty acid metabolism in male rat liver through activating rat PPARα signaling. However, whether this mode of action can translate to humans remained largely unclear. In this study, based on luciferase assays, C10-13-CPs (56.5% Cl) at concentrations greater than 1 µM (i.e., 362 µg/L) showed weak agonistic activity toward human PPARα (hPPARα) signaling. But in HepG2 cells, exposure to C10-13-CPs (56.5% Cl) at the human internal exposure level (100 µg/L) down-regulated expressions of most of the tested hPPARα target genes, which encode for enzymes that oxidize fatty acids. In line with the gene expression data, metabolomics further confirmed that exposure to four SCCP standards with varying chlorine contents at 100 µg/L significantly suppressed oxidation of fatty acids in HepG2 cells, mainly evidenced by elevations in both total fatty acids and long-chain acylcarnitines. In addition, exposure to these SCCPs also caused a shift in carbohydrate metabolism from the tricarboxylic acid cycle (TCA cycle) to aerobic glycolysis. Overall, the results revealed that SCCPs could inhibit hPPARα-mediated fatty acid oxidation, and stimulated aerobic glycolysis in HepG2 cells.


Assuntos
Hidrocarbonetos Clorados , Parafina , Animais , China , Ciclo do Ácido Cítrico , Monitoramento Ambiental , Ácidos Graxos , Glicólise , Humanos , Hidrocarbonetos Clorados/análise , Masculino , PPAR alfa/genética , Parafina/análise , Ratos
19.
Clin Transl Med ; 11(2): e296, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33635004

RESUMO

BACKGROUND: The human liver possesses a remarkable capacity for self-repair. However, liver fibrosis remains a serious medical concern, potentially progressing to end-stage liver cirrhosis and even death. Liver fibrosis is characterized by excess accumulation of extracellular matrix in response to chronic injury. Liver regenerative ability, a strong indicator of liver health, is important in resisting fibrosis. In this study, we provide evidence that ursodesoxycholic acid (UDCA) can alleviate liver fibrosis by promoting liver regeneration via activation of the ID1-WNT2/hepatocyte growth factor (HGF) pathway. METHODS: Bile duct ligation (BDL) and partial hepatectomy (PH) mouse models were used to verify the effects of UDCA on liver fibrosis, regeneration, and the ID1-WNT2/HGF pathway. An Id1 knockdown mouse model was also used to assess the role of Id1 in UDCA alleviation of liver fibrosis. RESULTS: Our results demonstrate that UDCA can alleviate liver fibrosis in the BDL mice and promote liver regeneration via the ID1-WNT2/HGF pathway in PH mice. In addition, Id1 knockdown abolished the protection afforded by UDCA in BDL mice. CONCLUSIONS: We conclude that UDCA protects against liver fibrosis by proregeneration via activation of the ID1-WNT2/HGF pathway.

20.
J Sep Sci ; 44(9): 1805-1814, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33569908

RESUMO

Extensive pharmacological research has demonstrated that Clerodendranthi Spicati Herba has an obvious anti-hyperglycemic effect via α-glucosidase inhibitory activity. However, the anti-hyperglycemic active fraction and its metabolic behavior in vivo have not been elaborated clearly. In this study, ultra-high-performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry with data filtering strategy, including mass defect screening, diagnostic product ions and neutral loss identification, was established for chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba. A total of 28 methoxylated flavonoids and 61 diterpenoids were rapidly identified. Four main known methoxylated flavonoids were purified and unambiguously identified by nuclear magnetic resonance analysis. Thirty-one absorbed diterpenoids, 12 absorbed methoxylated flavonoids, and 56 methoxylated flavonoids metabolites were identified in rat plasma, urine, bile, and feces after oral administration of anti-hyperglycemic active fraction. The methoxylated flavonoids were predominantly metabolized by demethylation, sulfation, and glucuronidation. Glucuronidation metabolites found in bile and urine after demethylation were dominant metabolites. Diterpenoids were absorbed into the blood mainly in the form of prototypes and excreted through bile and urine. These results indicated that methoxylated flavonoids and diterpenoids were responsible for α-glucosidase inhibitory activity, which might provide novel drug candidates for the management of diabetes mellitus.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...