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1.
Risk Anal ; 44(4): 958-971, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37496473

RESUMO

AI thermal facial recognition (AITFR) has been rapidly applied globally in the fight against Coronavirus disease 2019 (COVID-19). However, AITFR has also been accompanied by a controversy regarding whether the public accepts it. Therefore, it is necessary to assess the acceptance of AITFR during the COVID-19 crisis. Drawing upon the theory of acceptable risk and Siegrist's causal model of public acceptance (PA), we built a combined psychological model that included the perceived severity of COVID-19 (PSC) to describe the influencing factors and pathways of AITFR acceptance. This model was verified through a survey conducted in Xi'an City, Shaanxi Province, China, which collected 754 valid questionnaires. The results show that (1) COVID-19 provides various application scenarios for AI-related technologies. However, the respondents' trust in AITFR was found to be very low. Additionally, the public appeared concerned about the privacy disclosure issue and the accuracy of the AITFR algorithm. (2) The PSC, social trust (ST), and perceived benefit (PB) were found to directly affect AITFR acceptance. (3) The PSC was found to have a significant positive effect on perceived risk (PR). PR was found to have no significant effect on PA, which is inconsistent with the findings of previous studies. (4) The PB were found to be a stronger mediator of the indirect effect of the PSC on ST induced by AITFR acceptance.


Assuntos
COVID-19 , Reconhecimento Facial , Humanos , Confiança , Modelos Psicológicos , Inteligência Artificial
2.
Clin Anat ; 35(7): 979-986, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35842771

RESUMO

The aim of this study was to achieve accurate localization of the body surface position and depth of the center of the intramuscular nerve dense region (CINDR) of the pelvic floor muscles and to establish a target site for treating pelvic floor muscle spasm or weakness. Thirty-six adult cadavers were studied in the prone position. To locate the CINDR of the levator ani and coccygeus muscles, horizontal (H) and longitudinal (L) reference lines were used. Sihler's staining revealed the intramuscular nerve dense region of the pelvic floor muscles. The CINDR was labeled with barium sulfate and spiral computed tomography scanning, and three-dimensional reconstructions were obtained. The anterior and posterior CINDR projection points (P and P'), the position of point P projected on to the H and L lines (PH and PL ), and the CINDR depth were determined using the Syngo system. The PH of the CINDR of the levator ani and the coccygeus muscle were located at (24.73 ± 0.17)% and (15.93 ± 0.31)% of the H line, respectively. The PL were located at (84.30 ± 2.47)% and (6.76 ± 0.93)% of the L line. The puncture depth of the levator ani muscle was located at (5.56 ± 0.53) cm, and the depth of the coccygeus muscle at (22.08 ± 2.11)% of the PP' line. The body surface position and depth of the CINDR of the pelvic floor muscles were conducive to locating the target more efficiently and enhancing the efficacy of botulinum toxin A injection for treating pelvic floor muscle spasm and weakness with electrical stimulation or biofeedback.


Assuntos
Diafragma da Pelve , Dor Pélvica , Adulto , Humanos , Músculo Esquelético/inervação , Diafragma da Pelve/diagnóstico por imagem , Dor Pélvica/terapia , Períneo , Espasmo
3.
Molecules ; 27(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35335346

RESUMO

In the present study, we confirmed that α-asaronol, which is a product of the active metabolites of alpha Asarone, did not affect n-butylphthalide efficacy when n-butylphthalide and α-asaronol were co-administered to rats with cerebral ischemia-reperfusion injury. Our research revealed that the co-administration of α-asaronol and n-butylphthalide could further improve neurological function, reduce brain infarct volume, increase the number of Nissl bodies, and decrease the ratios of apoptotic cells and the expression of the caspase-3 protein for cerebral ischemia-reperfusion injury model compared to n-butylphthalide alone. Additionally, α-asaronol could significantly decrease the incidence of post-stroke epilepsy versus n-butylphthalide. This study provides valuable data for the follow-up prodrug research of α-asaronol and n-butylphthalide.


Assuntos
Epilepsia , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Anisóis , Incidência , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
4.
Molecules ; 27(11)2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35684409

RESUMO

A drug-drug multicomponent crystal consisting of metformin (MET) and dobesilate (DBS) was prospectively connected by solvent cooling and evaporating co-crystallization using the multicomponent crystal strategy, not only to optimize the physicochemical properties of single drugs, but also to play a role in the cooperative effect of DBS with the potential vascular protective effects of MET against diabetic retinopathy (DR). The crystal structure analysis demonstrated that MET and DBS were coupled in a 3D supramolecular structure connected by hydrogen-bonding interactions with a molar ratio of 1:1. Almost all hydrogen bond donors and receptors of MET and DBS participated in the bonding, which hindered the combination of remaining potential hydrogen bond sites and water molecules, resulting in a lower hygroscopicity property than MET alone.


Assuntos
Metformina , Cristalização , Ligação de Hidrogênio , Metformina/química , Água/química , Molhabilidade
5.
Drug Dev Res ; 82(8): 1111-1123, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33733518

RESUMO

CQMUH-011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti-inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 µg/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH-011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH-011 pretreatment can dose-dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH-011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down-regulated the expression of p-NF-κB and related proteins in the liver tissues. Furthermore, CQMUH-011 could maintain the balance of CD3+ CD4+ /CD3+ CD8+ and decrease the percentages of CD8+ CD69+ and CD4+ CD25+/- CD69+ T-cells in the splenocytes of ConA-challenged mice. Moreover, we found thatCD4+ CD25+/- CD69+ T-cells were significantly correlated with ALT levels, especially CD4+ CD25- CD69+ T-cells. In conclusion, CQMUH-011 exerts potential protective effects against ConA-induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4+ CD25- CD69+ and CD8+ CD69+ subsets in the spleen. CQMUH-011 also reduced the early apoptosis of lymphocytes in the thymus.


Assuntos
Adamantano , Anti-Inflamatórios , Hepatite Autoimune , Sulfonamidas , Linfócitos T , Animais , Feminino , Camundongos , Adamantano/análogos & derivados , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/sangue , Centro Germinativo/efeitos dos fármacos , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
6.
Molecules ; 26(14)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34299653

RESUMO

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.


Assuntos
Barbital/química , Metformina/química , Modelos Moleculares , Cristalografia por Raios X , Ligação de Hidrogênio , Estrutura Molecular
7.
Med Sci Monit ; 26: e920851, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32116289

RESUMO

BACKGROUND Spalt-like protein 4 (SALL4) is a nuclear transcription factor central to early embryonic development, especially for regulating pluripotency of embryonic stem cells (ESCs) and sustaining ESCs self-renewal. Aberrant re-expression of SALL4 in adult tissues is involved in tumorigenesis and cancer progression. However, the role of SALL4 in angiogenesis remains elusive. Here, we determined the potential action of SALL4 on proliferation, migration, and tube formation of endothelial cells. MATERIAL AND METHODS HUVECs were infected with lentiviral particles expressing shRNA against SALL4. QRT-PCR and immunoblotting analysis were carried out to evaluate knockdown efficiency at mRNA and protein levels. Cell proliferation was measured by CCK-8 assay and flow cytometry was conducted to analyze cell cycle distribution. Wound-healing and Transwell migration assays were performed to evaluate cell motility. In addition, we determined the role of SALL4 on angiogenesis by tube formation assay, and Western blot analysis was used to assess the effect of SALL4 downregulation on VEGFA expression. RESULTS We found that SALL4 downregulation resulted in decreased proliferation. Cell cycle analysis revealed that SALL4 knockdown impeded cell cycle progression and induced cell cycle arrest at G1 phase. We also found that silencing of SALL4 decreased the capacity of wound healing and cell migration in HUVECs. Furthermore, tube formation assay showed that loss of SALL4 inhibited HUVECs angiogenesis. We also observed that SALL4 knockdown reduced the level of VEGFA in HUVECs. CONCLUSIONS In conclusion, these results support that by promoting proliferation, cell cycle progression, migration, and tube formation, SALL4 is involved in the process of angiogenesis through modulating VEGFA expression.


Assuntos
Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais/fisiologia , Neovascularização Fisiológica/fisiologia , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Angiogênicas/metabolismo , Fase G1 , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Transdução de Sinais
8.
Molecules ; 25(18)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32962058

RESUMO

A co-crystal of rosiglitazone (Rsg) with berberine (Bbr), Rsg-Bbr, was prepared by the solvent evaporation method and characterized. The results showed that the electrostatic attraction existed between the nitrogen anion of rosiglitazone and the quaternary ammonium cation of berberine, and C-H···O hydrogen bonds were formed between Rsg and Bbr. In the crystal structure, rosiglitazone molecules stack into a supramolecular layer through π-π interactions while π-π interactions between berberine cations also result in a similar layer. The co-crystal presented a low moisture adsorption curve in the range of 0-95% relative humidity values at 25 °C. The improved dissolution rate of rosiglitazone in pH = 6.8 buffer solution could be achieved after forming co-crystal.


Assuntos
Berberina/química , Rosiglitazona/química , Berberina/síntese química , Cristalografia por Raios X , Ligação de Hidrogênio , Conformação Molecular , Teoria Quântica , Solubilidade , Eletricidade Estática
9.
Molecules ; 25(6)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188020

RESUMO

Both rosiglitazone and metformin have effects on blood glucose regulation and the proliferation of liver cancer cells. Combination therapy with these two drugs is common and effective for the treatment of diabetes in the clinic, however, the application of these two drugs is influenced by the poor dissolution of rosiglitazone and the gastrointestinal side-effect of metformin resulting from a high solubility. The formation of a multidrug crystal form (Rsg-Met) by a solvent evaporation method can solve the solubility issue. Crystal structure data and intramolecular hydrogen bonds were detected by X-ray diffraction and infrared spectroscopy. Surprisingly, Rsg-Met shortens the time spent in solubility equilibrium and multiplies the dissolution rate of Rsg. Finally, we found that a low concentration of Rsg-Met enhanced the proliferation inhibition effect on liver cancer cells (HepG2, SK-hep1) compared with rosiglitazone, without affecting the human normal cell line LO2.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cristalização , Humanos , Ligação de Hidrogênio , Conformação Molecular , Probabilidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X
10.
Cancer Cell Int ; 19: 13, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30651718

RESUMO

BACKGROUND: Rosiglitazone metformin adduct (RZM) is a novel compound, synthesized from rosiglitazone (Ros) and metformin (Met) combined at a molar mass ratio of 1:1. Met and Ros are widely used together for treating type 2 diabetes to improve drug effectiveness and reduce adverse drug reactions. Recent studies reported that both Met and Ros may possess antineoplastic properties in several cancers, including hepatocellular carcinoma (HCC). However, the effects of RZM in HCC and its underlying mechanisms remain unknown. METHODS: RZM was synthesized from Ros and Met at an equal molar ratio and identified by infrared spectroscopy. MTS and colony formation assays were performed to detect proliferative repression of RZM, the mixture, Met and Ros, respectively. Tumorigenesis assay in vivo was used to confirm the anti-tumorigenesis potential of RZM and Met. Moreover, cellular apoptosis caused by RZM was analyzed by hoechst staining assay and flow cytometry. RT-qPCR and western blotting were performed to reveal mechanisms for the function of RZM. RESULTS: Both in vitro and in vivo data showed that low doses of RZM enhanced inhibitory effect on HCC cells growth compared with Met. Flow cytometry analysis confirmed that treatment with RZM at 1 mM for 48 h triggered HCC cells apoptosis. RT-qPCR and western blotting analyses showed that p21 was upregulated in response to 1 mM RZM treatment. Furthermore, RZM could increase AMPK activation compared with Met. The increased p21 expression induced by RZM treatment was attenuated by an AMPK inhibitor compound C. CONCLUSIONS: All these observations demonstrate that RZM increases the antiproliferative effect of Met in HCC via upregulating p21 expression in an AMPK-dependent manner. Our results suggest that RZM has the potential to be an adjuvant for HCC therapy.

11.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640214

RESUMO

A multidrug crystal based on drug combinations was synthesized by the solvent evaporation method. This multicomponent crystal consisted of antidiabetic drugs Glimepiride (Gli) and Metformin (Met), which was performed by single crystal X-ray structure analysis. The results showed an enhancement of the pharmaceutical properties such as lower hygroscopicity and greater accelerated stability than the parent drug Met, and a higher solubility and dissolution rate than Gli.


Assuntos
Hipoglicemiantes/síntese química , Metformina/química , Compostos de Sulfonilureia/química , Química Farmacêutica , Cristalografia por Raios X , Combinação de Medicamentos , Hipoglicemiantes/química , Solubilidade , Molhabilidade
12.
J Cell Biochem ; 119(7): 5449-5459, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29369427

RESUMO

Pioglitazone/metformin adduct is a novel compound synthesized from pioglitazone and metformin combined at a molar mass ratio of 1:1. The aim of this study was to investigate the effects of pioglitazone/metformin adduct on high glucose-induced insulin secretion and apoptosis in INS-1 cells. Western blot and CCK8 analyses showed that the death rate of INS-1 cells increased in response to glucose treatment in a concentration-dependent manner. ELISA assays and Western blot analyses showed that insulin secretion peaked following treatment with glucose concentration at 33.33 mM. Treatment of INS-1 cells with 1 µM pioglitazone/metformin adduct in the presence of 33.33 mM glucose greatly improveded the levels of insulin and apoptosis rates compared to those of the control group. Analysis of mechanism underlying these effects revealed the involvement of the p21-p53-MDM2 signaling pathway. Our results indicate that pioglitazone/metformin adduct is superior to pioglitazone and/or metformin in regulating high glucose-induced insulin secretion and apoptosis in INS-1 cells.


Assuntos
Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Metformina/farmacologia , Pioglitazona/farmacologia , Animais , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Sinergismo Farmacológico , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ratos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Pharmazie ; 73(9): 494-497, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30223930

RESUMO

Pazopanib (trade name Votrient®) is a potent and selective multi-targeted tyrosine kinase inhibitor that blocks tumor growth and inhibits angiogenesis. Based on a recently reported procedure, we herein report the first synthesis of four potential process impurities generated in the production of pazopanib. The structure of these impurities were synthesized and characterized by 1H NMR, 13C NMR and HRMS data. The possible formation mechanisms of these impurities were also elucidated. These findings should be useful for the quality control of pazopanib in manufacture.


Assuntos
Inibidores da Angiogênese/química , Contaminação de Medicamentos , Inibidores de Proteínas Quinases/química , Pirimidinas/química , Sulfonamidas/química , Indazóis , Espectroscopia de Ressonância Magnética/métodos , Controle de Qualidade
14.
Pak J Pharm Sci ; 31(4): 1393-1397, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30033425

RESUMO

2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (IV), a key intermediate of saxagliptin for type 2 diabetes mellitus (T2DM), was prepared from 1-adamantanecarboxylic acid(I) via oxidation by potassium permanganate(KMnO4) to afford 3-hydroxy-1-adamantanecarboxylic acid (II), which was treated with a one-pot method to give 1-acetyl-3-hydroxyadamantane (III) followed by oxidation. Some key steps were optimized and the overall yield was about 51%.


Assuntos
Acetatos/síntese química , Adamantano/análogos & derivados , Adamantano/síntese química , Técnicas de Química Sintética/métodos , Dipeptídeos/química , Hipoglicemiantes/síntese química , Acetatos/química , Acetatos/farmacologia , Adamantano/química , Adamantano/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Estrutura Molecular , Permanganato de Potássio/química
15.
Saudi Pharm J ; 23(5): 581-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26594126

RESUMO

The aim of this study was to prepare the rosiglitazone sodium enteric-coated tablets and investigate its release rate. The rosiglitazone sodium enteric-coated tablet was prepared by single punch tablet press using substituted hydroxypropyl cellulose and polyvinylpyrrolidone (PVP). The release rate from the enteric-coated tablet of rosiglitazone sodium was evaluated. The release rate study showed that few rosiglitazone sodium was released from enteric coated formulation within 2 h in simulated gastric juice, while it released more than 80% of the labeled amount in 30 min in simulated intestinal juice. The preparing method of rosiglitazone sodium enteric-coated tablets was simple and had a good reproducibility. The release condition and determined methods could be used for the routine determinations of rosiglitazone sodium enteric-coated tablets.

16.
Anat Sci Int ; 99(1): 127-137, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37768515

RESUMO

The innervation of the pelvic wall muscles is not very clear. This study aimed to reveal the division of neuromuscular compartments and localize the surface position and depth of the center of the intramuscular nerve-dense region (CINDR) of the pelvic wall muscles based on Sihler's staining. Twenty-four adult cadavers were used. To localize the CINDR of the pelvic wall muscles, horizontal (H) and longitudinal (L) reference lines were drawn, and Sihler's staining was used to reveal the intramuscular nerve distribution. The CINDR projection points (P and P' points) behind and in front of the body surface, the positions of the P points projected onto the H and L lines (PH and PL points), and the depth of CINDR were determined by spiral computed tomography scanning. The piriformis and obturator internus muscles can be divided into two and three neuromuscular compartments, respectively. The PH of CINDR of the piriformis muscle was located at 22.61 ± 2.66% of the H line, the PL was at 28.53 ± 6.08% of the L line, and the puncture depth of the piriformis muscle was at 24.64 ± 2.16% of the PP' line. The PH of CINDR of the obturator internus muscle was at 16.49 ± 1.20% of the H line, the PL was at 10.94 ± 1.09% of its L line, and the puncture depth was 6.26 ± 0.38 cm. These findings may guide the design of the compartmentalized transplantation of the pelvic wall muscles and improve the target localization efficiency and efficacy for injecting botulinum toxin A to treat pelvic wall muscle spasm.


Assuntos
Músculo Esquelético , Adulto , Humanos , Coloração e Rotulagem , Músculo Esquelético/inervação , Cadáver
17.
Front Microbiol ; 14: 1100747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37032862

RESUMO

Spaceflight and microgravity has a significant impact on the immune, central nervous, bone, and muscle support and cardiovascular systems. However, limited studies are available on the adverse effects of long-term microgravity on the intestinal microbiota, metabolism, and its relationships. In this study, a ground-based simulated microgravity (SMG) mouse model was established to evaluate the impact of long-term microgravity on gut microbiota and metabolome. After 8 weeks of SMG, alterations of the intestinal microbiota and metabolites were detected using 16S rRNA sequencing and untargeted metabolomics. Compared to the control, no significant differences in α-diversity were observed at weeks 2, 4 and 8. Nevertheless, there were clear differences in community structures at different time points. The phylum Verrucomicrobia significantly declined from 2 to 8 weeks of SMG, yet the relative abundance of Actinobacteria and Deferribacteres expanded remarkably at weeks 8. SMG decreased the genus of Allobaculum and increased Bacteroides significantly throughout the period of 8 weeks. Besides, Genus Akkermansia, Gracilibacter, Prevotella, Odoribacter, Rothia, Sporosarcina, Gracilibacter, Clostridium, and Mucispirillum were identified as biomarkers for SMG group. Desulfovibrio_c21_c20, Akkermansia_muciniphila, and Ruminococcus_gnavus dropped at week 2, which tend to recover at week 4, except for Akkermansia_muciniphila. Bacteroides_uniformis and Faecalibacterium_prausnitzii declined significantly, while Ruminococcus_flavefaciens and Mucispirillum_schaedleri elevated at week 8. Furthermore, intestinal metabolome analysis showed that 129 were upregulated and 146 metabolites were downregulated in SMG. Long-term SMG most affected steroid hormone biosynthesis, tryptophan, cysteine, methionine, arginine, proline metabolism, and histidine metabolism. Correlated analysis suggested that the potential beneficial taxa Allobaculum, Akkermansia, and Faecalibacterium were negatively associated with tryptophan, histidine, arginine, and proline metabolism, but positively with steroid hormone biosynthesis. Yet Bacteroides, Lachnospiraceae_Clostridium, Rothia, Bilophila, and Coprococcus were positively correlated with arginine, proline, tryptophan, and histidine metabolism, while negatively associated with steroid hormone biosynthesis. These results suggest that Long-term SMG altered the community of intestinal microbiota, and then further disturbed intestinal metabolites and metabolic pathways, which have great potential to help understand and provide clues for revealing the mechanisms of long-term SMG involved diseases.

18.
Comput Math Methods Med ; 2022: 2929605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35726228

RESUMO

Monoclonal antibodies and antibody-derived biologics are essential tools for cancer research and therapy. The development of monoclonal antibody treatments for successful tumor-targeted therapies took several decades. A nanobody constructed by molecular engineering of heavy-chain-only antibody, which is unique in camel or alpaca, is a burgeoning tools of diagnostic and therapeutic in clinic. In this study, we immunized a 4-year-old female alpaca with TIM-3 antigen. Then, a VHH phage was synthesized from the transcriptome of its B cells by nested PCR as an intermediate library; the library selection for Tim-3 antigen is carried out in three rounds of translation. The most reactive colonies were selected by periplasmic extract monoclonal ELISA. The nanobody was immobilized by metal affinity chromatography (IMAC) purification with the use of a Ni-NTA column, SDS-PAGE, and Western blotting. Finally, the affinity of TIM3-specific nanobody was determined by ELISA. As results, specific 15 kD bands representing nanomaterials were observed on the gel and confirmed by Western blotting. The nanobody showed obvious specific immune response to Tim-3 and had high binding affinity. We have successfully prepared a functional anti-human Tim-3 nanobody with high affinity in vitro.


Assuntos
Anticorpos de Domínio Único , Ensaio de Imunoadsorção Enzimática , Feminino , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Mucina-3 , Linfócitos T
19.
Life Sci ; 298: 120515, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367243

RESUMO

AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been extensively used for the treatment of type 2 diabetes mellitus. Nevertheless, side effects like sore throat and diarrhea also occur in DPP-4 inhibitors treatment. The study aims to identify and develop novel DPP-4 inhibitors with better therapeutic profiles. MATERIALS AND METHODS: Here we synthesized a series of vildagliptin analogs, and among which, ZD-2 showed the moderate inhibition of DPP-4 activity compared with vildagliptin. High-fat-diet (HFD) mice were treated with ZD-2 (4.5 and 7.5 mg/kg) or vildagliptin (6 mg/kg) for 7 weeks following the examinations of metabolic index and pancreatic ß-cell function. Mouse pancreatic cell line MIN6 was used to evaluate ß-cell function, and intestinal enteroendocrine cell line STC-1 was used to evaluate the expression of gut hormones. KEY FINDINGS: The IC50 of ZD-2 was over 30-fold higher than vildagliptin. However, both ZD-2 and vildagliptin treatment showed comparable effects on improving glucose tolerance and reducing the steatosis of liver and fat mass in HFD mice. Moreover, ZD-2 exerted ß-cell-protective actions by preserving islet ß-cell mass and increasing the expression of functional ß-cell-related genes. Additionally, ZD-2 also stimulated the expression of gut hormones in STC-1 cells. SIGNIFICANCE: ZD-2 showed comparable anti-diabetic activities in HFD-fed mice although its lower potency on inhibition of DPP-4 compared with vildagliptin. Protection of ß-cell function might contribute to its anti-diabetic effects.


Assuntos
Adamantano , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Controle Glicêmico , Hormônios/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Camundongos Obesos , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Pirrolidinas/farmacologia , Vildagliptina/farmacologia , Vildagliptina/uso terapêutico
20.
Front Pharmacol ; 13: 842879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571083

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice. Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate. Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells. Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.

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