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1.
Int J Biol Macromol ; 273(Pt 2): 133040, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38857721

RESUMO

Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-ß1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.


Assuntos
Quitosana , Flavonóis , Lipossomos , Animais , Quitosana/química , Quitosana/farmacologia , Lipossomos/química , Flavonóis/farmacologia , Flavonóis/administração & dosagem , Camundongos , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/lesões , Fígado/patologia , Antioxidantes/farmacologia , Antioxidantes/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos
2.
Microbiol Spectr ; : e0023224, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912811

RESUMO

Soil salinization usually occurs in arid and semi-arid climate areas from 37 to 50 degrees north latitude and 73 to 123 degrees east longitude. These regions are inhabited by a large number of Coleopteran insects, which play an important role in the ecological cycle. However, little is known about the endosymbiotic microbial taxa and their biological characteristics in these insects. A study of endosymbiotic microorganisms of Coleoptera from Xinjiang, a typical arid and inland saline area, revealed that endosymbiont bacteria with salinity tolerance are common among the endosymbionts of Coleoptera. Functional prediction of the microbiota analysis indicated a higher abundance of inorganic ion transporters and metabolism in these endosymbiont strains. Screening was conducted on the tolerable 11% NaCl levels of Brevibacterium casei G20 (PRJNA754761), and differential metabolite and proteins were performed. The differential metabolites of the strain during the exponential and plateau phases were found to include benzene compounds, organic acids, and their derivatives. These results suggest that the endosymbiotic microorganisms of Coleoptera in this environment have adaptive evolution to extreme environments, and this group of microorganisms is also one of the important resources for mining saline and alkaline-tolerant chassis microorganisms and high-robustness enzymes. IMPORTANCE: Coleoptera insects, as the first largest order of insect class, have the characteristics of a wide variety and wide distribution. The arid and semi-arid climate makes it more adaptable. By studying the endosymbiont bacteria of Coleoptera insects, we can systematically understand the adaptability of endosymbiont bacteria to host and special environment. Through the analysis of endosymbiont bacteria of Coleoptera insects in different saline-alkali areas in arid and semi-arid regions of Xinjiang, it was found that bacteria in different host samples were resistant to saline-alkali stress. These results suggest that bacteria and their hosts co-evolved in response to this climate. Therefore, this study is of great significance for understanding the endosymbiont bacteria of Coleoptera insects and obtaining extremophile resources (Saline-alkali-resistant chassis strains with modification potential for the production of bulk chemicals and highly robust industrial enzymes).

3.
World Neurosurg ; 187: e585-e597, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38679374

RESUMO

BACKGROUND: Debate persists over the relative merits of neuroendoscopic surgery (NS) compared to stereotactic aspiration (SA) for treating supratentorial intracerebral hemorrhage (ICH). Consequently, we undertook this meta-analysis to assess the efficacy and safety of NS versus SA. METHODS: We searched for the all-relevant studies systematically from English databases including PubMed, Embase, Web of Science, and the Cochrane Library. Three independent researchers identified and selected these literatures that met the inclusion criteria. Then we evaluated the quality of these studies according to the Cochrane Collaboration's risk of bias tool and the Newcastle-Ottawa Scale. RevMan 5.4 statistical software was used to conduct this meta-analysis. RESULTS: Sixteen studies, including 2722 supratentorial ICH patients, were included in our meta-analysis. The pooled results showed that NS could effectively improve the functional prognosis (P = 0.002), reduce the postoperative mortality (P < 0.00001), and increase the hematoma evacuation rate (P < 0.00001). In addition, SA had more advantages in shortening operation time (P < 0.00001) and reducing intraoperative blood loss (P < 0.0001). However, there was no obvious statistical difference in intensive care unit stays (P = 0.23) between NS and SA. Besides, no sufficient evidence could support a significant difference in hospital stays. In the aspect of complications, NS was discovered to have a positive effect on preventing rebleeding (P = 0.005) and intracranial infection (P = 0.003). However, no significant differences between the 2 groups in digestive tract ulcer (P = 0.34), epilepsy (P = 0.99), and pneumonia (P = 0.58) were discovered. In the subgroup analysis, factors including publication time, Glasgow Coma Scale score, age, and follow-up, all significantly influenced the good functional outcome and mortality. Meanwhile, NS behaved more advantageous in improving functional prognosis for patients with hematoma located in the basal ganglia. CONCLUSIONS: NS may hold more advantages over SA in the treatment of supratentorial ICH. However, SA is also an effective and suitable alternative for elderly patients, especially those with multiple comorbidities intolerant to extended surgical procedures. Further high-quality studies are warranted to substantiate our findings in the future.


Assuntos
Hemorragia Cerebral , Neuroendoscopia , Técnicas Estereotáxicas , Humanos , Neuroendoscopia/métodos , Hemorragia Cerebral/cirurgia , Resultado do Tratamento , Sucção/métodos
4.
Carbohydr Polym ; 336: 122115, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670750

RESUMO

To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.


Assuntos
Proliferação de Células , Quitosana , Hidrogéis , Lipossomos , Osteoblastos , Quercetina , Quercetina/análogos & derivados , Crânio , Via de Sinalização Wnt , Animais , Quitosana/análogos & derivados , Quitosana/química , Quitosana/farmacologia , Quercetina/farmacologia , Quercetina/química , Lipossomos/química , Via de Sinalização Wnt/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Crânio/efeitos dos fármacos , Crânio/patologia , Crânio/metabolismo , Ratos , Regeneração Óssea/efeitos dos fármacos , Ratos Sprague-Dawley , Osteogênese/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Diferenciação Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Masculino , Simulação de Acoplamento Molecular
5.
Int J Biol Macromol ; 262(Pt 1): 129937, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325683

RESUMO

Diabetic wounds are typically chronic wounds and the healing process is limited by problems such as high blood glucose levels, bacterial infections, and other issues that make wound healing difficult. Designing drug-loaded wound dressings is an effective way to promote diabetic wound healing. In this study, we developed an SA/PVA nanofiber (SPS) containing Shikonin (SK) for the treatment of diabetic wounds. The prepared nanofibers were uniform in diameter, had good hydrophilicity and high water vapor permeability, and effectively promoted gas exchange between the wound site and the outside world. The results of in vitro experiments showed that SPS was effective in antimicrobial, antioxidant, and biocompatible. In vivo tests showed that the wound healing rate of mice treated with SPS reached 85.5 %. Immunohistochemical staining results showed that SPS was involved in the diabetic wound healing process through the up-regulation of growth factors (CD31, HIF-1α) and the down-regulation of inflammatory factors (CD68). Western blotting experiments showed that SPS attenuated the inflammation through the inhibition of the IκBα/NF-κB signaling pathway. These results suggest that SPS is a promising candidate for future clinical application of chronic wound dressings.


Assuntos
Diabetes Mellitus , Nanofibras , Naftoquinonas , Animais , Camundongos , Álcool de Polivinil/farmacologia , Alginatos/farmacologia , Cicatrização , Antibacterianos/farmacologia
6.
Int J Biol Macromol ; 263(Pt 1): 130256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38368995

RESUMO

The current clinical treatment of diabetic wounds is still based on oxygen therapy, and the slow healing of skin wounds due to hypoxia has always been a key problem in the repair of chronic skin injuries. To overcome this problem, the oxygen-producing matrix CaO2NPS based on the temperature-sensitive dihydromyricetin-loaded hydrogel was prepared. In vitro activity showed that the dihydromyricetin (DHM) oxygen-releasing temperature-sensitive hydrogel composite (DHM-OTH) not only provided a suitable oxygen environment for cells around the wound to survive but also had good biocompatibility and various biological activities. By constructing a T2D wound model, we further investigated the repairing effect of DHM-OTH on chronic diabetic skin wounds and the mechanisms involved. DHM-OTH was able to reduce inflammatory cells and collagen deposition and promote angiogenesis and cell proliferation for diabetic wound healing. These in vitro and in vivo data suggest that DHM-OTH accelerates diabetic wound repair as a novel method to efficiently deliver oxygen to wound tissue, providing a promising strategy to improve diabetic wound healing.


Assuntos
Quitosana , Diabetes Mellitus Experimental , Flavonóis , Animais , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Poloxâmero/farmacologia , Quitosana/farmacologia , Cicatrização , Oxigênio , Diabetes Mellitus Experimental/tratamento farmacológico , Bandagens
7.
ACS Pharmacol Transl Sci ; 7(1): 212-221, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38230295

RESUMO

Antibody-drug conjugates (ADCs), integrating high specificity of antigen-targeting antibodies and high potency of cell-killing chemical drugs, have become one of the most rapidly expanding therapeutic biologics in oncology. Although ADCs were widely studied from multiple aspects, overall structural elucidation with comprehensive understanding of variants is scarcely reported. Here, for the first time, we present a holistic and in-depth characterization of an interchain cysteine-conjugated ADC, focusing on conjugation and charge heterogeneity, and in vitro biological activities. Conjugation mapping utilized a bottom-up approach, unraveled positional isomer composition, provided insights into the conjugation process, and elucidated how conjugation affects the physicochemical and biological properties of an ADC. Charge profiling combined bottom-up and top-down approaches to interrogate the origin of charge heterogeneity, its impact on function, and best practice for characterization. Specifically, we pioneered the utilization of capillary isoelectric focusing-mass spectrometry to decode not only critical post-translational modifications but also drug load and positional isomer distribution. The study design provides general guidance for in-depth characterization of ADCs, and the analytical findings in turn benefit the discovery and development of future ADCs.

8.
J Mater Chem B ; 12(5): 1307-1316, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38226460

RESUMO

Bacterial infection is a key factor affecting wound healing. Conventional treatments might lead to the widespread emergence of drug-resistant bacteria due to the long-term and excessive use of antibiotics. It is necessary to develop an antibiotic-free method for effective treatment of bacterial wound infections. In this work, we constructed an antibiotic-free polysaccharide-based hydrogel dressing (ATB) with near-infrared light-actuated on-demand botanicals release and hyperthermia for the synergistic treatment of wound infections. The ATB hydrogel dressing was made up of agarose as a support matrix, berberine hydrochloride as the active botanicals and TA-Fe(III) nanoparticles as NIR laser-activated photothermal reagents. The ATB hydrogel dressing showed spatiotemporal botanicals release and excellent photothermal properties with NIR irradiation. With the results of in vitro and in vivo antibacterial experiments, the antibiotic-free ATB hydrogel could synergistically eliminate bacteria and accelerate wound healing. Overall, the near-infrared light-responsive ATB hydrogel could provide a promising antibiotic-free strategy for the treatment of bacterial wound infections.


Assuntos
Hipertermia Induzida , Infecção dos Ferimentos , Humanos , Hidrogéis/farmacologia , Compostos Férricos , Hipertermia , Polissacarídeos/farmacologia , Raios Infravermelhos , Bandagens , Antibacterianos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico
9.
Int J Biol Macromol ; 259(Pt 2): 129356, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218300

RESUMO

Various types of skin wounds pose challenges in terms of healing and susceptibility to infection, which can have a significant impact on physical and mental well-being, and in severe cases, may result in amputation. Conventional wound dressings often fail to provide optimal support for these wounds, thereby impeding the healing process. As a result, there has been considerable interest in the development of multifunctional polymer matrix hydrogel scaffolds for wound healing. This review offers a comprehensive review of the characteristics of polysaccharide-based hydrogel scaffolds, as well as their applications in different types of wounds. Additionally, it evaluates the advantages and disadvantages associated with various types of multifunctional polymer and polysaccharide-based hydrogel scaffolds. The objective is to provide a theoretical foundation for the utilization of multifunctional hydrogel scaffolds in promoting wound healing.


Assuntos
Amputação Cirúrgica , Hidrogéis , Hidrogéis/farmacologia , Polímeros , Polissacarídeos/farmacologia , Cicatrização , Antibacterianos
10.
Int J Biol Macromol ; 259(Pt 1): 129124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38176509

RESUMO

The wound of diabetes has long-term excessive inflammation leading to wound fibrosis and scar formation. In the process of diabetic wound healing, good wound dressing is required for intervention. In this study, we designed a dihydromyricetin-loaded hydrogel (PCD) based on phellinus igniarius polysaccharide and l-arginine modified chitosan as an alternative material to promote diabetes wound healing. PCD had a uniform porous structure, good thermal stability, excellent mechanical properties, high water absorption, excellent antioxidant and anti-inflammatory activities and good biocompatibility and biodegradability. In addition, in the full-thickness skin trauma model of diabetes, PCD significantly inhibited the JNK signaling pathway to reduce inflammatory response, and significantly down-regulated the expression of TGF-ß1, Smad2, Smad3 and Smad4 to directly inhibit the TGF-ß/Smad signaling pathway to accelerate wound healing and slow down scar formation in diabetes mice. Therefore, PCD has a broad application prospect in promoting diabetes wound healing.


Assuntos
Quitosana , Diabetes Mellitus Experimental , Flavonóis , Phellinus , Camundongos , Animais , Quitosana/farmacologia , Quitosana/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Cicatriz , Hidrogéis , Transdução de Sinais
11.
Int J Biol Macromol ; 259(Pt 1): 129160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181908

RESUMO

The healing of wounds in diabetics is commonly delayed by recurring infections and persistent inflammation at the wound site. For this reason, we conducted a study using the electrospinning technique to create nanofiber membranes consisting of polyvinylpyrrolidone/chitosan (PVP/CS) and incorporated dihydromyricetin (DHM) into them. Infrared Fourier transform spectroscopy and scanning electron microscopy were used to analyze the nanofiber membrane. Experimental results in vitro have shown that PVP/CS/DHM has exceptional properties such as hydrophilicity, porosity, water vapor transport rate, antioxidant capacity, and antibacterial activity. Moreover, our study has demonstrated that the application of PVP/CS/DHM can significantly improve wound healing in diabetic mice. After an 18-day treatment period, a remarkable wound closure rate of 88.63 ± 1.37 % was achieved. The in vivo experiments revealed that PVP/CS/DHM can promote diabetic wound healing by suppressing the activation of TLR4/MyD88/NF-κB signaling pathway and enhancing autophagy-related protein as well as CD31 and HIF-1α expression in skin tissues. This study showed that PVP/CS/DHM is a promising wound dressing.


Assuntos
Quitosana , Diabetes Mellitus Experimental , Flavonóis , Nanofibras , Camundongos , Animais , Quitosana/química , Povidona , Diabetes Mellitus Experimental/tratamento farmacológico , Nanofibras/química , Cicatrização , Antibacterianos/química , Anti-Inflamatórios
12.
J Ultrasound Med ; 43(3): 439-453, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38070130

RESUMO

OBJECTIVES: Both contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance (CEMR) are important imaging methods for hepatocellular carcinoma (HCC). This study aimed to establish a model using preoperative CEUS parameters to predict microvascular invasion (MVI) in HCC, and compare its predictive efficiency with that of CEMR model. METHODS: A total of 93 patients with HCC (39 cases in MVI positive group and 54 cases in MVI negative group) who underwent surgery in our hospital from January 2020 to June 2021 were retrospectively analyzed. Their clinical and imaging data were collected to establish CEUS and CEMR models for predicting MVI. The predictive efficiencies of both models were compared. RESULTS: By the univariate and multivariate regression analyses of patients' clinical information, preoperative CEUS static and dynamic images, we found that serrated edge and time to peak were independent predictors of MVI. The CEUS prediction model achieved a sensitivity of 92.3%, a specificity of 83.3%, and an accuracy of 84.6% (Az: 0.934). By analyzing the clinical and CEMR information, we found that tumor morphology, fast-in and fast-out, peritumoral enhancement, and capsule were independent predictors of MVI. The CEMR prediction model achieved a sensitivity of 97.4%, a specificity of 77.8%, and an accuracy of 83.2% (Az: 0.900). The combination of the two models achieved a sensitivity of 84.6%, a specificity of 87.0%, and an accuracy of 86.2% (Az: 0.884). There was no significant statistical difference in the areas under the ROC curve of the three models. CONCLUSION: The CEUS model and the CEMR model have similar predictive efficiencies for MVI of HCC. CEUS is also an effective method to predict MVI before operation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Estudos Retrospectivos , Invasividade Neoplásica , Imageamento por Ressonância Magnética/métodos
13.
BMC Plant Biol ; 23(1): 656, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114925

RESUMO

AIMS: In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. METHODS: Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. RESULTS: In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. CONCLUSION: E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.


Assuntos
Enterobacter cloacae , Gossypium , Enterobacter cloacae/metabolismo , Gossypium/genética , Gossypium/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Desenvolvimento Vegetal , Estresse Salino
14.
Postepy Dermatol Alergol ; 40(5): 606-610, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028405

RESUMO

Introduction: Metformin has potential in treating patients with psoriasis, and this meta-analysis aims to explore the impact of metformin supplementation on treatment efficacy for psoriasis. Material and methods: The PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of metformin on treatment efficacy for patients with psoriasis. Results: Three RCTs were included in the meta-analysis. Overall, compared with control intervention for psoriasis, metformin intervention resulted in significantly increased psoriasis area severity index (PASI) 75% reduction (odds ratio (OR) = 22.02; 95% confidence interval (CI): 2.12 to 228.49; p = 0.01), and erythema, scaling and induration (ESI) 75% reduction (OR = 9.12; 95% CI: 2.13 to 39.02; p = 0.003), and was associated with substantially decreased fasting plasma glucose (FPG, standard mean difference (SMD) = -0.59; 95% CI: -0.92 to -0.26; p = 0.0005), triglycerides (SMD = -0.92; 95% CI: -1.38 to -0.47; p < 0.0001), total cholesterol (SMD = -0.77; 95% CI: -1.22 to -0.32; p = 0.00008), and low-density lipoprotein (LDL, SMD = -0.67; 95% CI: -1.12 to -0.23; p = 0.003). Conclusions: Metformin supplementation effectively improves treatment efficacy and metabolic syndrome in psoriasis patients.

15.
Molecules ; 28(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37836731

RESUMO

Skeletons play an important role in the human body, and can form gaps of varying sizes once damaged. Bone defect healing involves a series of complex physiological processes and requires ideal bone defect implants to accelerate bone defect healing. Traditional grafts are often accompanied by issues such as insufficient donors and disease transmission, while some bone defect implants are made of natural and synthetic polymers, which have characteristics such as good porosity, mechanical properties, high drug loading efficiency, biocompatibility and biodegradability. However, their antibacterial, antioxidant, anti-inflammatory and bone repair promoting abilities are limited. Flavonoids are natural compounds with various biological activities, such as antitumor, anti-inflammatory and analgesic. Their good anti-inflammatory, antibacterial and antioxidant activities make them beneficial for the treatment of bone defects. Several researchers have designed different types of flavonoid-loaded polymer implants for bone defects. These implants have good biocompatibility, and they can effectively promote the expression of angiogenesis factors such as VEGF and CD31, promote angiogenesis, regulate signaling pathways such as Wnt, p38, AKT, Erk and increase the levels of osteogenesis-related factors such as Runx-2, OCN, OPN significantly to accelerate the process of bone defect healing. This article reviews the effectiveness and mechanism of biomaterials loaded with flavonoids in the treatment of bone defects. Flavonoid-loaded biomaterials can effectively promote bone defect repair, but we still need to improve the overall performance of flavonoid-loaded bone repair biomaterials to improve the bioavailability of flavonoids and provide more possibilities for bone defect repair.


Assuntos
Materiais Biocompatíveis , Flavonoides , Humanos , Materiais Biocompatíveis/farmacologia , Flavonoides/farmacologia , Antioxidantes/farmacologia , Osteogênese , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Regeneração Óssea
16.
Front Genet ; 14: 1234263, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701623

RESUMO

Introduction: Cervical cancer remains a significant global health burden, and Doxorubicin is a crucial therapeutic agent against this disease. However, the precise molecular mechanisms responsible for its therapeutic effects are not fully understood. Methods: In this study, we employed a multi-omics approach that combined transcriptomic and metabolomic analyses with cellular and in vivo experiments. The goal was to comprehensively investigate the molecular landscape associated with Doxorubicin treatment in cervical cancer. Results: Our unbiased differential gene expression analysis revealed distinct alterations in gene expression patterns following Doxorubicin treatment. Notably, the ANKRD18B gene exhibited a prominent role in the response to Doxorubicin. Simultaneously, our metabolomic analysis demonstrated significant perturbations in metabolite profiles, with a particular focus on L-Ornithine. The correlation between ANKRD18B gene expression and L-Ornithine levels indicated a tightly controlled gene-metabolite network. These results were further confirmed through rigorous cellular and in vivo experiments, which showed reductions in subcutaneous tumor size and significant changes in ANKRD18B, L-Ornithine, and Doxorubicin concentration. Discussion: The findings of this study underscore the intricate interplay between transcriptomic and metabolomic changes in response to Doxorubicin treatment. These insights could have implications for the development of more effective therapeutic strategies for cervical cancer. The identification of ANKRD18B and L-Ornithine as key components in this process lays the groundwork for future research aiming to unravel the complex molecular networks that underlie Doxorubicin's therapeutic mechanism. While this study provides a solid foundation, it also highlights the necessity for further investigation to fully grasp these interactions and their potential implications for cervical cancer treatment.

17.
Front Pediatr ; 11: 1199489, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484777

RESUMO

Background: Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the GNPTAB gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists. Methods: Sanger sequencing of the GNPTAB gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively. Results: The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT. Conclusion: MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.

18.
Biomed Pharmacother ; 165: 115177, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37467650

RESUMO

UVB radiation can damage human skin, whereas Ginsenoside Rg3, the active ingredient in red ginseng that is processed from ginseng (Panax ginseng C.A. Meyer), could inhibit UVB induced cell damage through anti-oxidation. Meanwhile, P407/CS/HA hydrogel has significant biomedical applications as carriers of drugs. However, the beneficial effects of Rg3-loaded hydrogel (Rg3-Gel) on human HaCaT keratinocytes induced by UVB have rarely been reported. In our study, Rg3 was loaded into hydrogel and the effect of Rg3-Gel against UVB­induced Hacat cells damages was determined by measuring its ability to alleviate UVB­induced elevation of oxidative stress, pro-inflammatory and apoptotic response. We found that the treatment with Rg3-Gel inhibited the generation of intracellular ROS and MDA and upregulated the expression of antioxidant enzymes SOD and GSH-Px which were inhibited by UVB exposure. Increased levels of pro-inflammatory cytokines TNF­α, COX­2, iNOS and IL­1ß following UVB irradiation were suppressed by the introduction of Rg3-Gel. Additionally, the level of Bcl-2 was decreased and the expression of Bax and Caspase3 were enhanced by Rg3-Gel treatment. In conclusion, Rg3-Gel equipped with the synergistic effect of Rg3 and hydrogel has an effective inhibitory effect on UVB-induced oxidative stress, inflammatory and apoptosis.


Assuntos
Células HaCaT , Hidrogéis , Humanos , Células HaCaT/metabolismo , Hidrogéis/farmacologia , Linhagem Celular , Estresse Oxidativo , Queratinócitos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Apoptose , Raios Ultravioleta/efeitos adversos
19.
Int J Biol Macromol ; 249: 126014, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37517765

RESUMO

Inadequate angiogenesis and inflammation at the wound site have always been a major threat to skin wounds, especially for diabetic wounds that are difficult to heal. Therefore, hydrogel dressings with angiogenesis and antibacterial properties are very necessary in practical applications. This study reported a hydrogel (PCA) based on L-arginine conjugated chitosan (CA) and aldehyde functionalized polysaccharides of Phellinus igniarius (OPPI) as an antibacterial and pro-angiogenesis dressing for wound repair in diabetes for the first time. and discussed its possible mechanism for promoting wound healing. The results showed that PCA had good antioxidant, antibacterial, biological safety and other characteristics, and effectively promoted the healing course of diabetic wound model. In detail, the H&E and Masson staining results showed that PCA promoted normal epithelial formation and collagen deposition. The Western blot results confirmed that PCA decreased the inflammation by inhibiting the IKBα/NF-κB signaling pathway and enhanced angiogenesis by adjusting the level of HIF-1α. In conclusion, PCA is a promising candidate for promoting wound healing in diabetes. Graphic abstract.


Assuntos
Quitosana , Diabetes Mellitus , Humanos , Hidrogéis/farmacologia , Quitosana/farmacologia , Cicatrização , Antibacterianos , Arginina , Inflamação , Polissacarídeos/farmacologia
20.
Molecules ; 28(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37446725

RESUMO

The skin, the largest organ in the human body, mainly plays a protective role. Once damaged, it can lead to acute or chronic wounds. Wound healing involves a series of complex physiological processes that require ideal wound dressings to promote it. The current wound dressings have characteristics such as high porosity and moderate water vapor permeability, but they are limited in antibacterial properties and cannot protect wounds from microbial infections, which can delay wound healing. In addition, several dressings contain antibiotics, which may have bad impacts on patients. Natural active substances have good biocompatibility; for example, ginsenoside Rg3 has anti-inflammatory, antibacterial, antioxidant, and other biological activities, which can effectively promote wound healing. Some researchers have developed various polymer wound dressings loaded with ginsenoside Rg3 that have good biocompatibility and can effectively promote wound healing and reduce scar formation. This article will focus on the application and mechanism of ginsenoside Rg3-loaded dressings in wounds.


Assuntos
Polímeros , Cicatrização , Humanos , Bandagens , Antibacterianos/farmacologia , Hidrogéis
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