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1.
Biomater Sci ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38939985

RESUMO

The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.

2.
J Mater Chem B ; 12(22): 5360-5376, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38700242

RESUMO

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.


Assuntos
Bioimpressão , Condrogênese , Hidrogéis , Células-Tronco Mesenquimais , Regeneração , Condrogênese/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Células-Tronco Mesenquimais/citologia , Regeneração/efeitos dos fármacos , Cartilagem Articular , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Engenharia Tecidual , Metacrilatos/química , Sobrevivência Celular/efeitos dos fármacos , Cartilagem/metabolismo , Cartilagem/citologia , Células Cultivadas , Humanos
3.
Adv Sci (Weinh) ; : e2401269, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757665

RESUMO

Tumor microenvironment (TME) plays an important role in the tumor progression. Among TME components, cancer-associated fibroblasts (CAFs) show multiple tumor-promoting effects and can induce tumor immune evasion and drug-resistance. Regulating CAFs can be a potential strategy to augment systemic anti-tumor immunity. Here, the study observes that hydrogen treatment can alleviate intracellular reactive oxygen species of CAFs and reshape CAFs' tumor-promoting and immune-suppressive phenotypes. Accordingly, a controllable and TME-responsive hydrogen therapy based on a CaCO3 nanoparticles-coated magnesium system (Mg-CaCO3) is developed. The hydrogen therapy by Mg-CaCO3 can not only directly kill tumor cells, but also inhibit pro-tumor and immune suppressive factors in CAFs, and thus augment immune activities of CD4+ T cells. As implanted in situ, Mg-CaCO3 can significantly suppress tumor growth, turn the "cold" primary tumor into "hot", and stimulate systematic anti-tumor immunity, which is confirmed by the bilateral tumor transplantation models of "cold tumor" (4T1 cells) and "hot tumor" (MC38 cells). This hydrogen therapy system reverses immune suppressive phenotypes of CAFs, thus providing a systematic anti-tumor immune stimulating strategy by remodeling tumor stromal microenvironment.

4.
J Vis Exp ; (207)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38767380

RESUMO

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.


Assuntos
Bioimpressão , Carragenina , Carragenina/química , Bioimpressão/métodos , Microgéis/química , Impressão Tridimensional , Engenharia Tecidual/métodos , Hidrogéis/química , Alicerces Teciduais/química , Animais , Humanos
5.
J Biomater Appl ; : 8853282241258555, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821553

RESUMO

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications.

6.
Food Chem ; 450: 139300, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38640525

RESUMO

The present study aimed to investigate the impact of Flammulina velutipes polysaccharide (FVSP) on the rheological properties and structural alterations of myofibrillar protein (MP) and oxidized MP (OMP), utilizing techniques such as rhehometer, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In the unoxidized system, the addition of 5.00% FVSP significantly improved (p < 0.05) the storage and loss moduli of the composite gel and promoted the α-helix to ß-sheet transformation. These effects enhanced the protein's gel strength and water-holding capacity (WHC). In the oxidation system, 5.00% FVSP had significant effects (p < 0.05) on repair and improvement of the oxidized MP. These effects inhibited the cross-linking aggregation and degradation of the protein. In addition, the addition of FVSP significantly improved the gel properties of MPs after oxidation (p < 0.05), hindered fracture of the protein gel network structure. In summary, polysaccharides have a substantial effect on the functional characteristics of MP, and FVSP could potentially be applied in meat products.


Assuntos
Flammulina , Proteínas Musculares , Oxirredução , Polissacarídeos , Flammulina/química , Polissacarídeos/química , Animais , Proteínas Musculares/química , Suínos , Géis/química , Produtos da Carne/análise , Reologia , Miofibrilas/química
7.
Foods ; 13(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38397499

RESUMO

The present study investigated the impact of quinoa protein (QP) on the physicochemical properties, sensory quality, and oxidative stability of myofibrillar protein (MP) in pork patties during five freeze-thaw (F-T) cycles. It was observed that repeated F-T cycles resulted in a deterioration of pork patty quality; however, the incorporation of QP effectively mitigated these changes. Throughout the F-T cycles, the sensory quality of the QP-treated group consistently surpassed that of the control group. After five F-T cycles, the thiobarbituric acid reactive substance (TBARS) content in the control group was measured at 0.423 mg/kg, whereas it significantly decreased to 0.347 mg/kg in the QP-treated group (p < 0.05). Furthermore, QP inclusion led to a decrease in pH and an increase in water-holding capacity (WHC) within pork patties. Following five F-T cycles, Ca2+-ATPase activity exhibited a significant increase of 11.10% in the QP-treated group compared to controls (p < 0.05). Additionally, supplementation with QP resulted in elevated total sulfhydryl content and reduced carbonyl content, Schiff base content, and dityrosine content within myofibrillar proteins (MPs), indicating its inhibitory effect on MP oxidation. In particular, after five F-T cycles, total sulfhydryl content reached 58.66 nmol/mL for the QP-treated group significantly higher than that observed for controls at 43.65 nmol/mL (p < 0.05). While carbonyl content increased from 2.37 nmol/mL to 4.63 nmol/mL between the first and fifth F-T cycle for controls; it only rose from 2.15 nmol/mL to 3.47 nmol/mL in the QP-treated group. The endogenous fluorescence levels were significantly higher (p < 0.05) in the QP-treated group compared to controls. In conclusion, the addition of QP enhanced the quality of pork patties and effectively inhibited the oxidative denaturation of MP during F-T cycles.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38204237

RESUMO

BACKGROUND: Podocyte injury and inflammatory response are the core contributors to the pathogenesis of diabetic nephropathy. This study aims to identify novel regulatory miRNAs and elucidate their underlying mechanisms, which will help us understand the pathogenesis of diabetic nephropathy more comprehensively. MATERIALS AND METHODS: Different glucose concentrations were used to treat podocytes to mimic the pathology of diabetic nephropathy in vitro. Flow cytometry was used to determine cell apoptosis. Inflammatory cytokines released by podocytes were measured by using an enzymelinked immunosorbent assay (ELISA). Western Blot was used to detect the expression of PRKAB2 protein in podocytes. RESULTS: Genecard and g: profiler results revealed that miR-29b might be involved in regulating HG-induced cell injury. QRT-PCR indicated that HG-induced downregulation of miR-29b in podocytes. MiR-29b knockdown promoted cell apoptosis and inflammatory response in podocytes. MiR-29b overexpression repressed cell apoptosis and inflammatory response induced by high glucose treatment in podocytes. Luciferase reporter assay and Western Blot showed that miR-29b targeted PRKAB2 to negatively regulate PRKAB2 expression directly. Knockdown of PRKAB2 reversed the increased cell apoptosis and inflammation induced by miR-29b inhibitors. CONCLUSION: MiR-29b plays a role in inhibiting inflammation and apoptosis in high glucose (HG) treated podocytes by negatively regulating PRKAB2 expression. This study provides new potential targets and ideas for the treatment of diabetic nephropathy.


Assuntos
Apoptose , Nefropatias Diabéticas , Regulação para Baixo , Glucose , Inflamação , MicroRNAs , Podócitos , Podócitos/metabolismo , Podócitos/patologia , Podócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Glucose/toxicidade , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Regulação para Baixo/efeitos dos fármacos , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Camundongos , Linhagem Celular , Humanos , Mediadores da Inflamação/metabolismo
9.
Food Res Int ; 176: 113819, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163720

RESUMO

Meeting requirements for dietary proteins, especially of essential amino acids (EAAs), is critical for the life-long health of living organisms. However, defining EAA targets for preparing biologically-matched nutrition that satisfies metabolic requirements for protein remains challenging. Previous research has shown the advantages of 'exome matching' in representing the specific requirement of dietary AAs, where the target dietary AA profile was derived from in silico translation of the genome of an organism, specifically responsible for protein expression (the 'exome'). However, past studies have assessed these effects in only one sex, for few parameters (body mass and composition), and have used purified diets in which protein is supplied as a mixture of individual AAs. Here, for the first time, we utilise a computational method to guide the formulation of custom protein blends and test if exome matching can be achieved at the intact protein level, through blending standard protein ingredients, ultimately leading to optimal growth, longevity and reproductive function. Mice were provided ad libitum (ad lib) access to one of the four iso-energetic protein-limited diets, two matched and two mis-matched to the mouse exome target, and fed at a fixed protein energy level of 6.2%. During or following 13-weeks of feeding, the food intake, body growth, composition and reproductive functions were measured. Compared to the two mis-matched diets, male and female animals on the exome-matched diet with protein digestibility correction applied, exhibited significantly improved growth rates and final body mass. The feed conversion efficiency in the same diet was also increased by 62% and 40% over the worst diets for males and females, respectively. Male, not female, exhibited higher accretion of lean body mass with the matched, digestibility-corrected diet. All reproductive function measures in both sexes were comparable among diets, with the exception of testicular daily sperm production in males, which was higher in the two matched diets versus the mis-matched diets. The results collectively demonstrate the pronounced advantages of exome-matching in supporting body growth and improving feed conversion efficiency in both sexes. However, the potential impact of this approach in enhancing fertility needs further investigation.


Assuntos
Exoma , Sêmen , Masculino , Camundongos , Feminino , Animais , Dieta , Proteínas Alimentares , Longevidade
10.
J Pediatr Hematol Oncol ; 46(1): 15-20, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37882055

RESUMO

BACKGROUND: Long noncoding RNA (LncRNA) play a vital role in the development and pathophysiology of osteosarcoma (OS). However, the LncRNA activated by HES1-10 in OS has not been furthered investigated. This present study aims to show the possible function of Lnc-HES1-10 in OS. METHODS: Cell proliferation in vitro were assessed by the MTT assay, whereas the migration and invasion abilities of OS cell lines were measured by wound-healing migration assay and transwell invasion assay, respectively. Quantitative reverse transcriptase polymerase chain reaction and western blot analysis was used to detected the expression level of HES1-10. RESULTS: The present study demonstrated that the Lnc-HES1-10 is overexpressed in OS and associated with poor prognosis of patients. In addition, the results revealed that Lnc-HES1-10 is overexpressed in MG63 and 143B OS cell lines and promote proliferation on both cell lines in vitro. Furthermore, migration and invasion abilities of MG63 and 143B cells are suppressed after silencing Lnc-HES1-10. CONCLUSION: Our finding demonstrates that HES1-10 plays a crucial role in regulating OS growth and metastasis.


Assuntos
Neoplasias Ósseas , MicroRNAs , Osteossarcoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Osteossarcoma/patologia , Proliferação de Células/genética , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo
11.
Front Nutr ; 10: 1268580, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818336

RESUMO

This study investigated the effect of Flammulina velutipes polysaccharides (FVPs) on the myofibrillar protein (MP) oxidation protein and physicochemical properties of catfish surimi during 75 days of frozen storage at -18°C. FVP was added to surimi at 1%, 1.5%, and 2%, respectively; the degree of MP oxidation and the physicochemical properties of the surimi were investigated, and the microstructure of the surimi was observed by scanning electron microscopy (SEM). The results showed that the carbonyl content and the thiobarbituric acid reactive substances (TBARS) in the FVP groups were lower than those in the CK group (the blank surimi). In comparison, the total sulfhydryl content, solubility, and Ca2+-ATPase activity were higher than those in the CK group after 75 days of storage. The addition of FVP significantly increased the water-holding capacity (WHC), gel strength, elastic modulus (G'), and loss modulus (G") of surimi, and made the gel of surimi have stronger continuity and a denser structure. Therefore, FVP has a better cryoprotective effect on surimi. It improves the quality of surimi, decreases MP oxidation, and reduces lipid and water loss during frozen storage. The anti-freezing effect of FVP added at 2% was similar to that of commercial protectants (4% sucrose and 4% sorbitol).

12.
Adv Mater ; 35(41): e2301784, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37432882

RESUMO

Piezoelectric materials produce charges to directly act on cancer medium or promote the generation of reactive oxygen species (ROS) for novel tumor therapy triggered by sonography. Currently, piezoelectric sonosensitizers are mainly used to catalyze ROS generation by the band-tilting effect for sonodynamic therapy. However, it remains a challenge for piezoelectric sonosensitizers to produce high piezovoltages to overcome the bandgap barrier for direct charge generation. Herein, Mn-Ti bimetallic organic framework tetragonal nanosheets (MT-MOF TNS) are designed to produce high piezovoltages for novel sono-piezo (SP)-dynamic therapy (SPDT) with remarkable antitumor efficacy in vitro and in vivo. The MT-MOF TNS comprise non-centrosymmetric secondary building units of Mn-Ti-oxo cyclic octamers with charge heterogeneous components for piezoelectricity. The MT-MOF TNS promotes strong sonocavitation to induce piezoelectric effect with a high SP voltage (2.9 V) in situ, to directly excite charges, which is validated by SP-excited luminescence spectrometry. The SP voltage and charges depolarize the mitochondrial and plasma membrane potentials and cause ROS overproduction and serious tumor cell damage. Importantly, MT-MOF TNS can be decorated with targeting molecules and chemotherapeutics for more severe tumor regression by combining SPDT with chemodynamic therapy and chemotherapy. This report develops a fascinating MT-MOF piezoelectric nano-semiconductor and provides an efficient SPDT strategy for tumor treatment.

13.
Asia Pac J Clin Nutr ; 32(2): 249-256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37382322

RESUMO

BACKGROUND AND OBJECTIVES: To investigate the association between frailty, malnutrition, comorbid medical conditions and activities of daily living (ADL) in older adult patients with fractures, and to analyse the influential factors of frailty. METHODS AND STUDY DESIGN: The FRAIL scale including five components: fatigue, resistance, ambulation, illness, and loss of weight, was used to evaluate frailty. Participants were divided into frailty, pre-frailty and non-frailty groups. The ADL was assessed using the Barthel Index, while the nutrition risk screening tool, NRS-2002, was used to assess the nutritional risk, and the Global Leadership Initiative on Malnutrition diagnostic criteria were used to diagnose the nutritional status. Statistical analysis was performed using univariate and multivariate logistic regression to determine the factors associated with frailty. RESULTS: A total of 166 patients were included in the study, and the incidences of frailty, pre-frailty and non-frailty were 39.2%, 33.1% and 27.7%, respectively. The severe dependence rate (ADL scale of <40) in the frailty, pre-frailty and non-frailty groups was 49.2%, 20.0% and 6.52%, respectively. The prevalence of nutritional risk was 33.7% (56/166), including 56.9% (31/65) in the frailty group and 32.7% (18/55) in the pre-frailty group. Of the 166 patients, 45 (27.1%) were diagnosed with malnutrition, including 47.7% (31/65) in the frailty group and 23.6% (13/55) in the pre-frailty group. CONCLUSIONS: Frailty in older adult patients with fractures is widespread, and the prevalence of malnutrition is high. The occurrence of frailty may be related to an advanced age, increased medical comorbidity and impairment in ADL.


Assuntos
Fragilidade , Desnutrição , Humanos , Idoso , Estado Nutricional , Prevalência , Atividades Cotidianas , Desnutrição/epidemiologia , Fragilidade/complicações , Fragilidade/epidemiologia
14.
Nutr Clin Pract ; 38(5): 1063-1072, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37073095

RESUMO

BACKGROUND: To analyze the current situation of frailty and the main influencing factors of frailty of older patients with hip fracture. METHODS: Using a fixed-point consecutive sampling method, we investigated older adult patients with hip fracture aged ≥60 years who were hospitalized in an orthopedic ward of a tertiary hospital from January 2021 to March 2022. We also assessed the prevalence of frailty and malnutrition by trial of the fatigue, resistance, aerobic capacity, illnesses, and loss of weight (FRAIL) scale and the Global Leadership Initiative on Malnutrition criteria to analyze the factors influencing frailty. RESULTS: A total of 216 older adult patients with hip fracture were collected, 106 (49.08%) were frail, 72 (33.33%) were prefrail, 38 (17.59%) were nonfrail, 103 (47.69%) were at overall nutrition risk, and 76 (35.19%) were malnourished. The results of bivariate correlation analysis showed that frailty score was correlated with age, the Activity of Daily Living Scale (ADL) score, body mass index (BMI), C-reactive protein, hemoglobin (Hb), serum albumin (ALB), and serum prealbumin, and was negatively correlated with ADL score, BMI, Hb, and ALB (r = -0.399, -0.420, -0.195, -0.283, respectively; P < 0.05). The results of multiple linear regression analysis showed that age, number of underlying diseases, ADL score, BMI score, and nutrition status were important influencing factors of frailty (P < 0.05). CONCLUSION: Older adult patients with hip fracture are frail and prefrail, with a high prevalence of malnutrition. Advanced age, combined underlying diseases, and a low BMI score were risk factors for preoperative frailty.


Assuntos
Fragilidade , Fraturas do Quadril , Desnutrição , Humanos , Idoso , Estado Nutricional , Fragilidade/epidemiologia , Desnutrição/epidemiologia , Desnutrição/etiologia , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Fatores de Risco
15.
Aging Dis ; 14(2): 529-547, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37008055

RESUMO

Hypoxia is an indispensable factor for cancer progression and is closely associated with the Warburg effect. Circular RNAs (CircRNA) have garnered considerable attention in molecular malignancy therapy as they are potentially important modulators. However, the roles of circRNAs and hypoxia in osteosarcoma (OS) progression have not yet been elucidated. This study reveals the hypoxia-sensitive circRNA, Hsa_circ_0000566, that plays a crucial role in OS progression and energy metabolism under hypoxic stress. Hsa_circ_0000566 is regulated by hypoxia-inducible factor-1α (HIF-1α) and directly binds to it as well as to the Von Hippel-Lindau (VHL) E3 ubiquitin ligase protein. Consequentially, binding between VHL and HIF-1α is impeded. Furthermore, Hsa_circ_0000566 contributes to OS progression by binding to HIF-1α (while competing with VHL) and by confers protection against HIF-1α against VHL-mediated ubiquitin degradation. These findings demonstrate the existence of a positive feedback loop formed by HIF-1α and Hsa_circ_0000566 and the key role they play in OS glycolysis. Taken together, these data indicate the significance of Hsa_circ_0000566 in the Warburg effect and suggest that Hsa_circ_0000566 could be a potential therapeutic target to combat OS progression.

16.
J Orthop Surg Res ; 18(1): 186, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36894989

RESUMO

The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1ß/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1ß/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA.


Assuntos
MicroRNAs , Osteoartrite , Humanos , Camundongos , Animais , MicroRNAs/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/uso terapêutico , Cartilagem/metabolismo , Condrócitos/metabolismo , Osteoartrite/metabolismo , Interleucina-1beta/metabolismo , Matriz Extracelular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Apoptose , Células Cultivadas
17.
Front Microbiol ; 14: 1156413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36970674

RESUMO

Introduction: Microbial inoculants can reinvent the value and edible security of cultured sausages. Various studies have demonstrated that starter cultures made up of Lactic acid bacteria (LAB) and Staphylococcus xylosus (known as L-S) isolated from traditional fermented foods were used in fermented sausage manufacturing. Methods: This study evaluated the impact of the mixed inoculation cultures on limiting biogenic amines, nitrite depletion, N-nitrosamine reduction, and quality metrics. Inoculation of sausages with the commercial starter culture (SBM-52) was evaluated for comparison. Results and discussion: Results showed that the L-S strains could rapidly decrease the water activity (Aw) and pH of fermented sausages. The ability of the L-S strains to delay lipid oxidation was equivalent to the SBM-52 strains. The non-protein nitrogen (NPN) contents of L-S-inoculated sausages (0.31%) were higher than that of SBM-52-inoculated sausages (0.28%). After the ripening process, the nitrite residues in the L-S sausages were 1.47 mg/kg lower than in the SBM-52 sausages. Compared to the SBM-52 sausages, there was a 4.88 mg/kg reduction in the biogenic amines' concentrations in L-S sausage, especially for histamine and phenylethylamine concentrations. The N-nitrosamine accumulations of the L-S sausages (3.40 ug/kg) were lower than that of the SBM-52 sausages (3.70 ug/kg), and the NDPhA accumulations of the L-S sausages were 0.64 ug/kg lower than that of the SBM-52 sausages. Due to their significant contributions to nitrite depletion, biogenic amine reduction, and N-nitrosamine depletion in fermented sausages, the L-S strains have the potential to serve as an initial inoculant in the process of manufacturing fermented sausages.

18.
World J Surg ; 47(3): 611-620, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36484804

RESUMO

PURPOSE: This meta-analysis aimed to investigate the effectiveness of conservative and surgical treatments of scaphoid fracture. METHODS: The literature databases of Pubmed, Cochrane library, and Embase were searched in March 2022. This work extracted the data based on healing time, grip strength, range of wrist motion, nonunion, time before returning to work, and complications (including persistent pain, malunion of the fracture, wound infection, scar sensitivity, hypertrophic scar, and implant-related complications). Stata 14.0 software was used for statistical analysis. RESULTS: Twelve RCTs studies met our inclusion criteria. The surgical group had a shorter healing-time and time before returning to work than the conservative group. In addition, the surgical group had significantly better grip strength and range of wrist motion than the conservative group (P < 0.01). However, there was no significant difference between nonunion (P = 0.538) and complications (P = 0.661) between the two groups. CONCLUSION: This meta-analysis showed that surgical treatment of scaphoid fracture achieved better grip strength and range of wrist motion, and had a lower healing time and time before returning to work than the conservative treatment. The two treatments had similar results in nonunion and complications. Further RCTs were required for the research.


Assuntos
Tratamento Conservador , Fraturas Ósseas , Osso Escafoide , Humanos , Tratamento Conservador/efeitos adversos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/terapia , Complicações Pós-Operatórias/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Amplitude de Movimento Articular , Osso Escafoide/lesões , Osso Escafoide/cirurgia , Resultado do Tratamento
19.
Front Nutr ; 9: 1047988, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479295

RESUMO

Active packaging films are designed to improve quality and extend the food shelf life by incorporating functional active ingredients into biopolymer films. This study developed a bioactive film based on chitosan (CS) and whey isolated protein (WPI) incorporated with 0.01 wt% TiO2 and 0.1 wt% white pepper essential oil (WPEO). The physicochemical properties of the prepared film were also evaluated comprehensively. The results showed that water solubility and water vapor permeability of the film incorporated with TiO2 and WPEO were 25.09% and 0.0933 g mm m-2 h-1 KPa-1, respectively, which were significantly higher than those of other films (P < 0.05). In addition, the UV barrier properties of films incorporating TiO2 and WPEO have improved. The films were characterized by Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The FTIR results showed interactions between TiO2 and WPEO with CS/WPI compound, and the SEM results indicated a good incorporation of TiO2 into the composite films. The antioxidative and antibacterial properties of films were significantly enhanced by incorporating WPEO. According to results, the developed biocomposite film can be considered as a packaging material.

20.
Front Nutr ; 9: 1048352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36458169

RESUMO

The effects of cooking modes [cooking in stainless-steel pot (SS), ceramic pot (CP), and electrical ceramic stewpot (EC) with different stewing time] on chemical compositions, whiteness, 5'-nucleotides, fatty acids (FAs), sensory quality and flavor substances in chicken soup added Clitocybe squamulose (Pers.) Kumm (a natural edible fungus) were investigated. The results showed that CP chicken soup had higher soluble solid matter (5.83 g/100 mL), total sugar (2.38 mg/mL), crude protein (7.58 g/100 g), and 5'-nucleotides (325.53 mg/mL) than EC and SS chicken soups. 48 volatile flavor compounds, mainly aldehydes and alkanes, were found by gas chromatography-mass spectrometry (GC-MS), and the characteristic flavor substances were identified by Principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Hexanal, (E,E)-2,4-decadienal and 3-methyl-hexadecane were the most abundant differential volatile compounds in the CP chicken soup. Additionally, the results of sensory evaluation showed that the chicken soup cooked in CP had the higher values of aroma, taste, and overall acceptability. Our results indicate that CP mode might be the best option for cooking chicken soup. This study provides a new perspective in the improvement of the quality and flavor of chicken soup by using an appropriate cooking mode. Theoretical support for the use of various cooking modes is also discussed to improve the quality of chicken soup at home and in the industry.

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