Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
1.
Biochem Pharmacol ; 225: 116334, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824967

RESUMO

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.


Assuntos
Apoptose , Fator de Transcrição STAT3 , Animais , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Etanol/toxicidade , Etanol/administração & dosagem , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/prevenção & controle , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética
2.
Int J Biol Macromol ; 264(Pt 2): 130568, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447822

RESUMO

Polysaccharide based self-healing and injectable hydrogels with reversible characteristics have widespread potential in protein drug delivery. However, it is a challenge to design the dynamic hydrogel for sequential release of protein drugs. Herein, we developed a novel mussel inspired sequential protein delivery dynamic polysaccharide hydrogel. The nanocomposite hydrogel can be fabricated through doping polydopamine nanoparticles (PDA NPs) into reversible covalent bond (imine bonds) crosslinked polymer networks of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CEC), named PDA NPs@OHA-l-CEC. Besides multiple capabilities (i.e., injection, self-healing, and biodegradability), the nanocomposite hydrogel can achieve sustained and sequential protein delivery of vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA). PDA NPs doped in hydrogel matrix serve dual roles, acting as secondary protein release structures and form dynamic non-covalent interactions (i.e., hydrogen bonds) with polysaccharides. Moreover, by adjusting the oxidation degree of OHA, the hydrogels with different crosslinking density could control overall protein release rate. Analysis of different release kinetic models revealed that Fickian diffusion drove rapid VEGF release, while the slower BSA release followed a Super Case II transport mechanism. The novel biocompatible system achieved sequential release of protein drugs has potentials in multi-stage synergistic drug deliver based on dynamic hydrogel.


Assuntos
Quitosana , Fator A de Crescimento do Endotélio Vascular , Nanogéis , Fator A de Crescimento do Endotélio Vascular/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Quitosana/química , Polissacarídeos/química , Ácido Hialurônico/química , Soroalbumina Bovina
3.
Updates Surg ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512634

RESUMO

Tension-free hernia repair is the gold standard for groin hernia repair. However, the optimal surgical treatment for incarcerated or strangulated groin hernia in elderly populations is controversial. The aim of this study is to compare the clinical efficacy of mesh repair and suture repair in the treatment of incarcerated or strangulated groin hernia in elderly patients. Patients ≥ 65 years who underwent urgent surgical repair for incarcerated or strangulated groin hernia from January 2012 to June 2022 were included. Patients' demographic data and postoperative outcomes were retrospectively analyzed. Patients with limited life expectancy were screened from the elderly population for subgroup analysis. A total of 103 patients (median age: 84 years old, range 65-96; mean follow-up time: 36.8 ± 24.8 months) were included, involving 42 cases in the suture repair group and 61 cases in the mesh repair group. Suture repair and mesh repair had similar lengths of ICU and hospital stay, and rates of small bowel resection, chronic pain, surgical site infection, and surgical-related death. However, suture repair had a significantly higher recurrence rate than mesh repair (7% vs. 2%, P = 0.04). In our subgroup analysis, for patients with limited life expectancy (41 patients; median age: 88 years old, range: 80-96), suture repair had no statistical difference in postoperative outcomes compared with mesh repair. Mesh repair is suitable for elderly patients with acutely incarcerated or strangulated groin hernias. However, for elderly patients with limited life expectancy, suture repair and mesh repair showed similar clinical outcomes.

4.
Cancer Biol Ther ; 25(1): 2321767, 2024 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-38417050

RESUMO

Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.


Assuntos
Aminoaciltransferases , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , NF-kappa B/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/genética
5.
Surg Endosc ; 37(12): 9651-9657, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37891372

RESUMO

BACKGROUND: Due to limited technical demand, single-port sleeve gastrectomy (SPSG) is a feasible laparoscopic technique for sleeve gastrectomy (SG). Nonetheless, difficulties exist when performing the single-port technique, and in this study, we aim to describe a slight maneuver that can improve the SPSG procedure. METHODS: Patients who underwent laparoscopic SG between January 2022 and May 2023 at our hospital were included. The patients were classified into two groups: (1) SPSG and (2) multiple-port SG (MPSG). The parameters for this analysis were the patients' age, gender, weight, body mass index (BMI), conversion rate, drainage placement, 30-day readmission rate, and postoperative complications. Postoperative one-month and three-month percentages of total weight loss (%TWL) were calculated and compared. RESULTS: 171 patients were included in this study: (1) the SPSG group (n = 96) and (2) the MPSG group (n = 75). No statistically significant difference was observed within the preoperative (age, gender, height, weight, and BMI) and the perioperative parameters between SPSG and MPSG (operation time, drainage placement, 30-day readmission) (p > 0.05). Per Clavien-Dindo's grading, two patients in the SPSG group suffered grade 1 complications; for the MPSG group, one patient sustained grade 2 and another suffered grade 3b complication. No statistical significance was observed on the %TWL between the two groups (p > 0.05). CONCLUSION: Our study found that performing SPSG in specific patient is feasible and non-inferior when compared to the MPSG. Further studies will be needed to elucidate better the efficacy and safety of performing SPSG.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade Mórbida/complicações , Gastrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Índice de Massa Corporal , Laparoscopia/métodos , Estudos Retrospectivos , Derivação Gástrica/efeitos adversos , Resultado do Tratamento
6.
Am J Cancer Res ; 13(7): 3234-3245, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37559988

RESUMO

Pegylated liposomal doxorubicin (PLD) has excellent therapeutic efficacy in the treatment of cancers, but can cause serious adverse reactions such as hand-foot syndrome (HFS). Our previous research suggests that both PLD-induced HFS may be associated with injury to tight junctions (TJs) in the skin and that calcium dobesilate (CaD) can alleviate HFS. However, the underlying molecular mechanism is not well understood. Here, we created an in vitro PLD-treated model using Human Microvascular Endothelial Cell line-1 (HMEC-1) and an in vivo HFS rat model to investigate the underlying pathways. Treatment with PLD increased the expression of HYAL-1, CD44, and hyaluronic acid (HA) concentration, while reducing ZO-1 and Claudin-5 expression. Moreover, PLD treatment induced the degradation of higher molecular weight HA to its lower molecular weight counterpart, elevating the permeability of both HEMC-1 cell membranes and rat paw skin capillaries. AD-01 (CD44 inhibitor) inhibited the effect of PLD on the expression of ZO-1 and Claudin-5. Furthermore, CaD treatment suppressed the expression of HYAL-1 and CD44, mitigated HA degradation, and enhanced the expression of ZO-1 and Claudin-5. This resulted in decreased permeability in HEMC-1 cells and rat skin capillaries. In summary, our data suggest that PLD may promote the destruction of TJs via the HA/CD44 pathway, thereby leading to HFS through increased skin permeability and exacerbated doxorubicin extravasation. Moreover, CaD can inhibit this pathway, offering a potential therapeutic avenue to alleviate HFS.

7.
World J Surg ; 47(10): 2416-2424, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37268782

RESUMO

AIM: To compare the efficacy and safety of synthetic and biological meshes in ventral hernia repair (VHR) and abdominal wall reconstruction (AWR). METHODS: We screened all clinical trials that reported the application of synthetic and biological meshes in VHR and AWR using Medline, Web of Science, and Embase (Ovid). Only comparative studies with similar baselines such as age, sex, body mass index, degree of wound contamination, and hernia defects between the intervention and control groups were included. Effect sizes with 95% confidence were pooled using a random- or fixed-effects model based on the size of heterogeneity. A sensitivity analysis was performed to test the stability of the results. RESULTS: Ten studies with 1305 participants were included. Biological meshes were associated with significantly higher recurrence rate (OR, 2.09; 95% CI 1.42-3.08; I2 = 50%), surgical site infection (OR, 1.47; 95% CI 1.10-1.97; I2 = 30%), higher re-admission rate (OR, 1.51; 95% CI 1.05-2.17; I2 = 50%), and longer length of hospital stay (SMD, 0.37; 95% CI 0.10-0.65; I2 = 72%). Similar surgical site occurrence, re-operation rate, and mesh explantation rate were observed among biological and synthetic meshes. Biological meshes have no difference in recurrence rate as compared to synthetic meshes, between the clean-contaminated, and contamination-infected fields (OR, 1.41; 95% CI 0.41-4.87 vs 3.00; 95% CI 1.07-8.46; P = 0.36). CONCLUSION: Synthetic meshes are a safe alternative to biological meshes for VHR and AWR. Considering the high cost of biological meshes, synthetic meshes are more appropriate for the VHR and AWR.


Assuntos
Parede Abdominal , Hérnia Ventral , Humanos , Parede Abdominal/cirurgia , Telas Cirúrgicas , Resultado do Tratamento , Hérnia Ventral/cirurgia , Hérnia Ventral/complicações , Medicina Baseada em Evidências
8.
Chem Commun (Camb) ; 59(18): 2592-2595, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36753236

RESUMO

A new dual-cationic amphiphilic AIEgen TPhBT-PyP with NIR emission and efficient 1O2 generation was designed. The amphiphilicity of TPhBT-PyP was tuned with dual-positive charges of pyridinium and TPP groups, efficiently targeting mitochondria and distinguishing Gram-positive bacteria. TPhBT-PyP performed well in photodynamic therapy, inducing cancer cell apoptosis and killing S. aureus bacteria.


Assuntos
Fotoquimioterapia , Staphylococcus aureus , Fotoquimioterapia/métodos , Mitocôndrias , Diagnóstico por Imagem , Bactérias Gram-Positivas , Cátions/farmacologia , Fármacos Fotossensibilizantes/farmacologia
9.
Environ Sci Technol ; 57(2): 1103-1113, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36574338

RESUMO

Anthracite is globally used as a filter material for water purification. Herein, it was found that up to 15 disinfection byproducts (DBPs) were formed in the chlorination of anthracite-filtered pure water, while the levels of DBPs were below the detection limit in the chlorination of zeolite-, quartz sand-, and porcelain sandstone-filtered pure water. In new-anthracite-filtered water, the levels of dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and ammonia nitrogen (NH3-N) ranged from 266.3 to 305.4 µg/L, 37 to 61 µg/L, and 8.6 to 17.1 µg/L, respectively. In aged anthracite (collected from a filter at a DWTP after one year of operation) filtered water, the levels of the above substances ranged from 475.1 to 597.5 µg/L, 62.1 to 125.6 µg/L, and 14 to 28.9 µg/L, respectively. Anthracite would release dissolved substances into filtered water, and aged anthracite releases more substances than new anthracite. The released organics were partly (around 5%) composed by the µg/L level of toxic and carcinogenic aromatic carbons including pyridine, paraxylene, benzene, naphthalene, and phenanthrene, while over 95% of the released organics could not be identified. Organic carbon may be torn off from the carbon skeleton structure of anthracite due to hydrodynamic force in the water filtration process.


Assuntos
Desinfetantes , Água Potável , Poluentes Químicos da Água , Purificação da Água , Água Potável/análise , Água Potável/química , Desinfecção , Cloro , Carvão Mineral , Cloretos , Carbono , Halogenação , Poluentes Químicos da Água/análise , Desinfetantes/análise
10.
Macromol Rapid Commun ; 44(3): e2200690, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36250440

RESUMO

Water-soluble 3D polymers with inherent nanoscale pores have been shown to be ideal platforms for the inclusion and delivery of drugs and hold a great promise as biocompatible materials for diagnostic and therapeutic purposes. Herein, a low cytotoxic water-soluble flexible organic framework FOF-S6 with a hydrodynamic diameter of about 127.5 nm is synthesized through the formation of a hydrazone bond from a semirigid tetraaldehyde and a flexible biacylhydrazines which contains a disulfide bond (1:2). FOF-S6 has the ability to dissociate and release inclusion complexes in response to weakly acidic media and glutathione (GSH) overexpressed in tumor cells. More importantly, a facile strategy is developed to contain and deliver aggregation-induced emission photosensitizers (AIE PS, TBD-DQA-540) and chemotherapeutic drugs (Doxorubicin hydrochloride, DOX). DOX-PS@FOF-S6 is synthesized by a one-pot method, which can realize efficient photo-chemotherapy under the guidance of fluorescence imaging, thereby improving the multidrug resistance of tumor cells and the instability of photosensitizers, so as to improve the tumor treatment efficacy.


Assuntos
Neoplasias , Fármacos Fotossensibilizantes , Humanos , Fármacos Fotossensibilizantes/química , Água , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Glutationa , Oxirredução , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
11.
JACS Au ; 2(7): 1686-1698, 2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35911443

RESUMO

FtmOx1 is a nonheme iron (NHFe) endoperoxidase, catalyzing three disparate reactions, endoperoxidation, alcohol dehydrogenation, and dealkylation, under in vitro conditions; the diversity complicates its mechanistic studies. In this study, we use two substrate analogues to simplify the FtmOx1-catalyzed reaction to either a dealkylation or an alcohol dehydrogenation reaction for structure-function relationship analysis to address two key FtmOx1 mechanistic questions: (1) Y224 flipping in the proposed COX-like model vs α-ketoglutarate (αKG) rotation proposed in the CarC-like mechanistic model and (2) the involvement of a Y224 radical (COX-like model) or a Y68 radical (CarC-like model) in FtmOx1-catalysis. When 13-oxo-fumitremorgin B (7) is used as the substrate, FtmOx1-catalysis changes from the endoperoxidation to a hydroxylation reaction and leads to dealkylation. In addition, consistent with the dealkylation side-reaction in the COX-like model prediction, the X-ray structure of the FtmOx1•CoII•αKG•7 ternary complex reveals a flip of Y224 to an alternative conformation relative to the FtmOx1•FeII•αKG binary complex. Verruculogen (2) was used as a second substrate analogue to study the alcohol dehydrogenation reaction to examine the involvement of the Y224 radical or Y68 radical in FtmOx1-catalysis, and again, the results from the verruculogen reaction are more consistent with the COX-like model.

12.
Front Plant Sci ; 13: 951003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36035662

RESUMO

Rhododendron (Ericaceae) not only has ornamental value, but also has great medicinal and edible values. Many Rhododendron species are native to acid soils where aluminum (Al) toxicity limits plant productivity and species distribution. However, it remains unknown how Rhododendron adapts to acid soils. Here, we investigated the physiological and molecular mechanisms of Al tolerance in Rhododendron yunnanense Franch. We found that the shoots of R. yunnanense Franch did not accumulate Al after exposure of seedlings to 50 µM Al for 7 days but predominantly accumulated in roots, suggesting that root Al immobilization contributes to its high Al tolerance. Whole-genome de novo transcriptome analysis was carried out for R. yunnanense Franch root apex in response to 6 h of 50 µM Al stress. A total of 443,639 unigenes were identified, among which 1,354 and 3,413 were up- and down-regulated, respectively, by 6 h of 50 µM Al treatment. Both Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that genes involved in "ribosome" and "cytoskeleton" are overrepresented. Additionally, we identified Al-tolerance homologous genes including a tonoplast-localized ABC transporter RyALS3; 1. Overexpression of RyALS3; 1 in tobacco plants confers transgenic plants higher Al tolerance. However, root Al content was not different between wild-type plants and transgenic plants, suggesting that RyALS3; 1 is responsible for Al compartmentalization within vacuoles. Taken together, integrative transcriptome, physiological, and molecular analyses revealed that high Al tolerance in R. yunnanense Franch is associated with ALS3; 1-mediated Al immobilization in roots.

13.
Adv Sci (Weinh) ; 9(29): e2202453, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35981878

RESUMO

Smart nanomaterials constitute a new approach toward safer and more effective combined anti-cancer immunotherapy. In this study, polydopamine-multiprotein conjugates (DmPCs) that can be used for targeted delivery of multiple proteins to cells, realize imaging and combine the advantages of multiple treatment methods (photothermal therapy, chemodynamic therapy, and immunotherapy) can be synthesized and characterized. Proteins, as biological agents, are frequently used in this context, given their low toxicity in vivo. To overcome protein instability and short half-life in vivo, the use of several proteins in combination with selected nanomaterials to treat patients with melanoma is proposed. In addition to the synthesis and characterization of protein-bound nanoparticles, it is further demonstrated that several proteins can be efficiently delivered to tumor sites. DmPCs have a wide range of potential adaptability, which provides new opportunities for proteins in the field of treatment and imaging.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Fatores Biológicos , Humanos , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico , Neoplasias/terapia , Fototerapia , Ligação Proteica
14.
J Immunol Res ; 2022: 3218452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571566

RESUMO

Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1ß) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5'-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.


Assuntos
Metformina , Encefalopatia Associada a Sepse , Sepse , Animais , Lipopolissacarídeos/farmacologia , Metformina/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Microglia/metabolismo , NF-kappa B/metabolismo , Prognóstico , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/patologia
15.
Chem Sci ; 13(12): 3589-3598, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35432880

RESUMO

Mononuclear non-heme iron enzymes are a large class of enzymes catalyzing a wide-range of reactions. In this work, we report that a non-heme iron enzyme in Methyloversatilis thermotolerans, OvoAMtht, has two different activities, as a thiol oxygenase and a sulfoxide synthase. When cysteine is presented as the only substrate, OvoAMtht is a thiol oxygenase. In the presence of both histidine and cysteine as substrates, OvoAMtht catalyzes the oxidative coupling between histidine and cysteine (a sulfoxide synthase). Additionally, we demonstrate that both substrates and the active site iron's secondary coordination shell residues exert exquisite control over the dual activities of OvoAMtht (sulfoxide synthase vs. thiol oxygenase activities). OvoAMtht is an excellent system for future detailed mechanistic investigation on how metal ligands and secondary coordination shell residues fine-tune the iron-center electronic properties to achieve different reactivities.

16.
Int J Biol Macromol ; 202: 657-670, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35066024

RESUMO

Chronic non-healing diabetic wounds and ulcers can be fatal, lead to amputations, and remain a major challenge to medical, and health care sectors. Susceptibility to infection and impaired angiogenesis are two central reasons for the clinical consequences associated with chronic non-healing diabetic wounds. Herein, we successfully developed calcium ion (Ca2+) cross-linked sodium alginate (SA) hydrogels with both pro-angiogenesis and antibacterial properties. Our results demonstrated that deferoxamine (DFO) and copper nanoparticles (Cu-NPs) worked synergistically to enhance the proliferation, migration, and angiogenesis of human umbilical venous endothelial cells in vitro. Results of colony formation assay indicated Cu-NPs were effective against E. coli and S. aureus in a dose-dependent manner in vitro. An SA hydrogel containing both DFO and Cu-NPs (SA-DFO/Cu) was prepared using a Ca2+ cross-linking method. Cytotoxicity assay and colony formation assay indicated that the hydrogel exhibited beneficial biocompatible and antibacterial properties in vitro. Furthermore, SA-DFO/Cu significantly accelerated diabetic wound healing, improved angiogenesis and reduced long-lasting inflammation in a mouse model of diabetic wound. Mechanistically, DFO and Cu-NPs synergistically stimulated the levels of hypoxia-inducible factor 1α and vascular endothelial growth factor in vivo. Given the pro-angiogenesis, antibacterial and healing properties, the hydrogel possesses high potential for clinical application in refractory wounds.


Assuntos
Diabetes Mellitus , Nanopartículas , Alginatos , Animais , Cálcio , Cobre , Desferroxamina/farmacologia , Escherichia coli , Células Endoteliais da Veia Umbilical Humana , Humanos , Hidrogéis/farmacologia , Camundongos , Staphylococcus aureus , Fator A de Crescimento do Endotélio Vascular , Cicatrização
17.
Nucleic Acids Res ; 49(21): 12048-12068, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34850126

RESUMO

N6-methyladenosine (m6A) modification is the most extensively studied epigenetic modification due to its crucial role in regulating an array of biological processes. Herein, Bsu06560, formerly annotated as an adenine deaminase derived from Bacillus subtilis 168, was recognized as the first enzyme capable of metabolizing the epigenetic nucleoside N6-methyladenosine. A model of Bsu06560 was constructed, and several critical residues were putatively identified via mutational screening. Two mutants, F91L and Q150W, provided a superiorly enhanced conversion ratio of adenosine and N6-methyladenosine. The CRISPR-Cas9 system generated Bsu06560-knockout, F91L, and Q150W mutations from the B. subtilis 168 genome. Transcriptional profiling revealed a higher global gene expression level in BS-F91L and BS-Q150W strains with enhanced N6-methyladenosine deaminase activity. The differentially expressed genes were categorized using GO, COG, KEGG and verified through RT-qPCR. This study assessed the crucial roles of Bsu06560 in regulating adenosine and N6-methyladenosine metabolism, which influence a myriad of biological processes. This is the first systematic research to identify and functionally annotate an enzyme capable of metabolizing N6-methyladenosine and highlight its significant roles in regulation of bacterial metabolism. Besides, this study provides a novel method for controlling gene expression through the mutations of critical residues.


Assuntos
Adenosina/análogos & derivados , Epigênese Genética , Regulação da Expressão Gênica , Adenosina/metabolismo , Desaminação , Humanos
18.
Ann Transl Med ; 9(18): 1459, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734011

RESUMO

BACKGROUND: Using bioinformatic methods to explore the differentially expressed genes (DEGs) of human idiopathic pulmonary fibrosis (IPF) and to elucidate the pathogenesis of IPF from the genetic level. METHODS: The GSE110147 gene expression profile was downloaded from the GEO database. The data of lung adenocarcinoma (LUAD) samples, lung squamous cell carcinoma (LUSC) samples and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. DEGs between IPF patients and healthy donors were analyzed using the GEO2R tool. Use the "clusterprofiler" package in R software to perform gene ontology (GO) and KEGG pathway enrichment analysis, and then perform function annotation and protein-protein interaction (PPI) network construction in the STRING online tool. The Genome Browser tool of the university of california santa cruz (UCSC) online website was used to predict transcription factors (TFs) of genes. In the final, the results were analyzed synthetically. RESULTS: A total of 9,183 DEGs were identified, of which 4,545 genes were down-regulated, and 4638 were up-regulated. MMP1, SPP1, and BPIFB1 were the top three DEGs with the highest significant up-regulation. These DEGs played an important role in the occurrence of IPF through the MAPK (mitogen-activated protein kinase) signaling pathway. Furthermore, 50 DEGs were enriched in the expression of PD-L1 and the PD-1 checkpoint pathway in cancer, of which 11 genes were re-enriched in the pathway of non-small cell lung cancer. The expression of the 11 genes were extensively regulated by CTCFL, SP2 and ZNF341. Most of them were differentially expressed between lung cancers and normal lung tissues. The overall survival (OS) curve of LUAD were significantly stratified by AKT2, KRAS, PIK3R1, meanwhile the OS curve of LUAC was significantly stratified by MAPK3. CONCLUSIONS: Bioinformatics analysis revealed that DEGs including MPP1 might be potential targets and biomarkers of IPF, and the MAPK signaling pathway is related to the occurrence and development of IPF. The development of IPF lung cancer complications may be related to the activation of genes enriched in PD-L1 expression and PD-1 checkpoint pathway, which provides clues to the pathogenesis of IPF combined with lung cancer.

19.
Ann Transl Med ; 9(10): 874, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164508

RESUMO

BACKGROUND: The incidence of abdominal wall metastasis from colorectal cancer (CRC) is very low, but it has a poor prognosis. Despite the advances in radiotherapy, chemotherapy, and targeted therapy, patient prognosis has not improved significantly. Through surgical treatment, some patients with locally advanced CRC with abdominal wall invasion can achieve tumor-free survival or an improved quality of life. METHODS: The clinical data of 15 patients in our department from January 2015 to January 2020 were retrospectively analyzed. All patients underwent preoperative three-dimensional reconstruction of the tumor and abdominal wall after discussion with a multidisciplinary team (MDT). Patient information, including tumor size, defect size, operation time, intraoperative bleeding, hospital stay, and other factors, was collected. RESULTS: All 15 patients underwent resection followed by reconstruction for locally advanced CRC with abdominal wall invasion. The average tumor area and abdominal wall defects were 98.13±71.70 and 270.07±101.95 cm2, respectively; and accurate abdominal wall classification and zoning were obtained for all patients. The average operation time was 431.7±189.2 min, and the average blood loss was 513.3±244.6 mL. The recurrence rates in the incisional hernia and abdominal wall were 6.0% and 13.3%, respectively. The patient survival rate was 87.7%. CONCLUSIONS: Surgical treatment of locally advanced CRC with abdominal wall invasion is feasible, but requires accurate and comprehensive preoperative evaluation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA