Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 235
Filtrar
1.
Nanoscale ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622908

RESUMO

Previous calculations of the dielectric and optical properties of 2D materials often overlooked or circumvented the influence of vacuum spacing introduced in periodic calculations, which gave rise to mispredictions of the intrinsic properties of 2D materials or merely qualitative results. We first elucidated the relationship between the vacuum spacing and the dielectric and optical properties of 2D materials in periodic calculations, and then formulated an effective method to accurately predict the dielectric and optical properties of 2D materials by restoring the intrinsic dielectric functions of 2D materials independent of the additional vacuum spacing. As examples, the intrinsic dielectric and optical properties of ultrathin hexagonal boron nitride (h-BN) and molybdenum sulphide (MoS2) from a monolayer to a pentalayer, including dielectric functions, optical absorption coefficients, refraction indexes, reflectivities, extinction coefficients, and energy loss functions, have been calculated by our method. Our calculations reveal that the out-of-plane optical dielectric constants, static refraction indexes, and static reflectivities of 2D h-BN and MoS2 increase as the number of layers increases, while the in-plane counterparts remain unchanged. The excitonic frequency-dependent optical properties of h-BN and MoS2 from a monolayer to bulk are also calculated by solving the Bethe-Salpeter equation and they show strong anisotropy. The present method shows better agreement with the experimental results compared to previous calculations and demonstrates enormous potential to investigate the dielectric and optical properties of other 2D materials extensively and quantitatively.

2.
Chemosphere ; 286(Pt 1): 131683, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34351278

RESUMO

Butachlor being an important member of chloroacetanilide herbicides, is frequently used in agriculture to control unwanted weeds. Exposure to butachlor can induce cancer, human lymphocyte aberration, and immunotoxic effects in animals. The current experimental trial was executed to determine the potential risks of herbicide butachlor to immunotoxicity and its mechanism of adverse effects on the spleen. For this purpose, mice were exposed to 8 mg/kg butachlor for 28 days, and the toxicity of butachlor on the spleen of mice was evaluated. We found that butachlor exposure led to an increase in serum ALB, GLU, TC, TG, and TP and changes in the morphological structure of the spleen of mice. More importantly, results showed that butachlor significantly increased the expression level of ATG-5, decreased the protein expression of LC3B and M-TOR, and significantly decreased the mRNA content of M-TOR and p62. Results revealed that the mRNA contents of APAF-1, CYTC, and CASP-9 related genes were significantly decreased after butachlor treatment. Subsequently, the mRNA levels of inflammatory cytokines (IL-1ß, TNF-α, IL-10) were reduced in the spleen of treated mice. This study suggested that butachlor induce spleen toxicity and activate the immune response of spleen tissue by targeting the CYTC/BCL2/M-TOR pathway and caspase cascading activation of spleen autophagy and apoptosis pathways which may ultimately lead to immune system disorders.

4.
Toxicology ; 461: 152906, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34450209

RESUMO

Fluoride is one of the most widely distributed elements in nature, while some fluorine-containing compounds are toxic to several vertebrates at certain levels. The current study was performed to evaluate the nephrotoxic effects of fluoride exposure in ducks. The results showed that the renal index was decreased in NaF group, and fluoride exposure significantly decreased the levels of serum Albumin, Glucose, Total cholesterol, Urea, protein and Triglycerides, confirming that NaF exhibited adverse effects on the kidney. The overall structure of renal cells showed damage with the signs of nuclelytic, vacuolar degeneration, atrophy, renal cystic cavity widening after fluoride induction. Renal vascular growth was impaired as the expression of VEGF and HIF-1α decreased (p > 0.05). More importantly, autophagy and apoptosis levels of CYT C, LC3, p62, Beclin, M-TOR, Bax and Caspase-3 were increased (p < 0.05) in the NaF treated group. Interestingly, our results showed that Phosphatidylethanolamine (PE) and Phosphatidylcholine (PC) activated the M-TOR autophagy pathway. Meanwhile, the PE acted on Atg5/ LC3 autophagy factor, followed by the auto-phagosome generation and activation of cell autophagy. These results indicate that NaF exposure to duck induced nephron-toxicity by activating autophagy, apoptosis and glucolipid metabolism pathways, which suggest that fluorine exposure poses a risk of poisoning.

5.
Bioelectromagnetics ; 42(6): 516-531, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34245597

RESUMO

The future of mankind is tied to the exploration and eventual colonization of space. Currently, people have resided in orbit at a space station. In the future, we will have opportunities to stay on the moon, Mars, or in deeper space, where astronauts are exposed to the hypomagnetic field (HMF), which refers to an extremely weak magnetic field environment compared with the geomagnetic field. However, the potential risks of HMF exposure to human health are often overlooked. Here, we summarize the literature related to the biological effects of HMF and calculate the magnitude of the effect. Briefly, HMF impairs multiple animal systems, especially in the central nervous system. Additionally, HMF is a stress factor in plant growth and reproduction. Finally, HMF combined with other space environments, such as radiation and microgravity, can affect organisms. Further studies are required to explore (i) countermeasures to the adverse effects of HMF, (ii) combined effects of HMF with other factors, and (iii) the intensity-effect relationship. © 2021 Bioelectromagnetics Society.

6.
Microb Pathog ; 158: 105106, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34311015

RESUMO

This study was ascertained to investigate the adverse effects of pathogenic E. coli on gut microbiota of Tibetan piglets with history of yellow and white dysentery. For this purpose, a total of 18 fecal samples were collected from infected and healthy Tibetan piglets for 16S rRNA gene amplification and sequencing of V3-V4 region. Results showed that Firmicutes, Bacteroidia Fusobacteriota, Proteobacteria and Actinobacteriota were the predominant bacteria in Tibetan piglets at the level of phylum classification. Results on classification at family level showed that Lactobacillus, Bacteroidota, Fusobacteriota and Enterobacteriaceae were the dominant bacteria. Results on classification of bacteria at phylum level compared with normal piglets indicated that Bacteroidota, Actinobacteriota, Euryarchaota and Spirochaetota in fecal microbial community in Tibetan piglets showing yellow dysenteric and diarrhea group were significantly decreased (P ≤ 0.05). Compared with the feces of healthy Tibetan piglets, the abundance of Escherichia-Shigella, Lactobacillus and Enterococcus increased significantly in feces of Tibetan piglets having yellow dysentery and white dysentery. Moreover, results exhibited that the Proteobacteria and Fusobacteriota were significantly increased (P ≤ 0.05) suggesting dominant microbial community. Results revealed that E. coli induced different pathological alterations in intestine including damage to intestinal epithelial cells, infiltration of inflammatory cells, presence of red blood cells in spaces of tissues, hemorrhages and necrosis of intestinal villi in piglets with history of yellow dysentery. This study for the first time reported the composition, characteristics, and differences of the fecal microflora diversity of Tibetan piglets with yellow and white dysentery in Qinghai-Tibet Plateau, which can provide a suitable support for effective control of diarrhoeal disease in these animals.


Assuntos
Escherichia coli , Microbiota , Animais , Escherichia coli/genética , Fezes , RNA Ribossômico 16S/genética , Suínos , Tibet
7.
Int J Mol Sci ; 22(13)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34281233

RESUMO

Osteosarcoma is a common malignant bone tumor in clinical orthopedics. Iron chelators have inhibitory effects on many cancers, but their effects and mechanisms in osteosarcoma are still uncertain. Our in vitro results show that deferoxamine (DFO) and deferasirox (DFX), two iron chelators, significantly inhibited the proliferation of osteosarcoma cells (MG-63, MNNG/HOS and K7M2). The viability of osteosarcoma cells was decreased by DFO and DFX in a concentration-dependent manner. DFO and DFX generated reactive oxygen species (ROS), altered iron metabolism and triggered apoptosis in osteosarcoma cells. Iron chelator-induced apoptosis was due to the activation of the MAPK signaling pathway, with increased phosphorylation levels of JNK, p38 and ERK, and ROS generation; in this process, the expression of C-caspase-3 and C-PARP increased. In an orthotopic osteosarcoma transplantation model, iron chelators (20 mg/kg every day, Ip, for 14 days) significantly inhibited the growth of the tumor. Immunohistochemical analysis showed that iron metabolism was altered, apoptosis was promoted, and malignant proliferation was reduced with iron chelators in the tumor tissues. In conclusion, we observed that iron chelators induced apoptosis in osteosarcoma by activating the ROS-related MAPK signaling pathway. Because iron is crucial for cell proliferation, iron chelators may provide a novel therapeutic strategy for osteosarcoma.


Assuntos
Deferasirox/uso terapêutico , Desferroxamina/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Sideróforos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Deferasirox/farmacologia , Desferroxamina/farmacologia , Humanos , Ferro/metabolismo , Camundongos , Osteossarcoma/metabolismo , Sideróforos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Commun Biol ; 4(1): 850, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239035

RESUMO

The retinal pigmented epithelium (RPE) is a monolayer of multifunctional cells located at the back of the eye. High membrane turnover and polarization, including formation of actin-based apical microvilli, are essential for RPE function and retinal health. Herein, we demonstrate an important role for ßA3/A1-crystallin in RPE. ßA3/A1-crystallin deficiency leads to clathrin-mediated epidermal growth factor receptor (EGFR) endocytosis abnormalities and actin network disruption at the apical side that result in RPE polarity disruption and degeneration. We found that ßA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPß) and that ßA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that ßA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P2 pool through PITPß/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity.


Assuntos
Polaridade Celular/fisiologia , Endocitose , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Cadeia A de beta-Cristalina/metabolismo , Animais , Polaridade Celular/genética , Proteínas do Citoesqueleto/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Camundongos Knockout , Fosfatidilinositol 4,5-Difosfato/metabolismo , Proteínas de Transferência de Fosfolipídeos/metabolismo , Fosforilação , Ligação Proteica , Epitélio Pigmentado da Retina/citologia , Cadeia A de beta-Cristalina/genética
9.
Eur J Pharmacol ; 906: 174219, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34081904

RESUMO

Heme oxygenase-1 (HO-1) exerts a protective effect against cell damage and induces the activity of many enzymes involved in the treatment of many human diseases, including osteoporosis. The increasing prevalence of osteoporosis and the limitations of the current treatments available led to a continuous occurrence of bone loss and osteoporotic fractures, highlighting the need of a better understanding of the mechanism and function of HO-1. Many factors cause osteoporosis, including lack of estrogen, aging, and iron overload, and they either cause the increase in inflammatory factors or the increase in reactive oxygen species to break bone reconstruction balance. Therefore, regulating the production of inflammatory factors and reactive oxygen species may become a strategy for the treatment of osteoporosis. Solid evidence showed that the overexpression of HO-1 compensates high oxidation levels by increasing intracellular antioxidant levels and reduces inflammation by suppressing pro-inflammatory factors. Some extracts can target HO-1 and ameliorate osteoporosis. However, no systematic report is available on therapies targeting HO-1 to combat osteoporosis. Therefore, this review summarizes the biological characteristics of HO-1, and the relationship between inflammatory response and reactive oxygen species production regulated by HO-1 and osteoporosis. The understanding of the role of HO-1 in osteoporosis may provide ideas for a potential clinical treatment and new drugs targeting HO-1.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34106484

RESUMO

KCTD15 is associated with body mass index and fat deposition in humans, mice and chickens. However, the function of KCTD15 in pig fat deposition remains unclear. In this study, we cloned and analysed the cDNA sequence of porcine KCTD15. The full length of the mRNA sequence of KCTD15 is 4,091 bp, encoding 283 amino acids. The protein is hydrophilic, it has a relative molecular mass of about 31.9 kDa and an isoelectric point of 7.09 with no signal peptide sequence or transmembrane structure. Expression analysis showed that KCTD15 expression level was significantly higher in the tissues of Large White pigs (LW) than in those of Tibetan pigs (TP) and Diannan Small-ear pigs (DN) at 6 months of age, whereas its expression level in embryonic tissues of LW at 60 days was lower than that in tissues of TP and Wujin pigs (WJ). In pig primary adipocytes, the expression level of KCTD15 is high in the early stage of differentiation and gradually decreases in later stages. Additionally, the single-nucleotide polymorphism (SNP) site T-2030C (T/C mutation, located 2,030 bp upstream of the start codon) showed a dominant allele T with high promoter activity in the LW population and a dominant allele C in the TP and WJ populations. Our results indicate that KCTD15 is involved in pig fat deposition and that T-2030C is an important regulatory site for transcriptional activity, affecting fat deposition.

11.
Bioelectromagnetics ; 42(5): 371-383, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082485

RESUMO

Static magnetic field (SMF) can alter cell fate decisions in many ways. However, the effects of SMF on cancer stem cells (CSCs) are little-known. In this particular study, we evaluate the biological effect of moderate-intensity SMF on osteosarcoma stem cells (OSCs) and try to clarify the underlying mechanisms of action. First, we demonstrated that prolonged exposure to SMF induced the proliferation and tumorsphere formation in K7M2 and MG63 OSCs. Moreover, SMF promoted the release of ferrous iron (Fe2+ ) and provoked reactive oxygen species (ROS) in OSCs. Interestingly, SMF evidently triggered the autophagic degradation of ferritin, which is characterized by the activation of microtubule-associated protein 1 light chain 3 (LC3) and nuclear receptor co-activator 4 (NCOA4), and downregulation of ferritin heavy chain 1 (FTH1) in OSCs. Particularly, the colony-forming ability of K7M2 OSCs promoted by SMF was obviously abolished by using a small interfering RNA (siRNA) against NCOA4. Finally, treatment of the tumor-bearing mice with SMF did not affect the tumor volume or tumor mass, nor pulmonary metastasis of K7M2 OSCs, but the SMF-treated K7M2 OSCs caused a preference of pulmonary metastasis in a mouse model, which suggested that SMF might induce the metastatic characteristic of OSCs. Consequently, this paper demonstrates for the first time that the cumulative SMF exposure promoted the self-renewal ability of OSCs via autophagic degradation of ferritin, implying that ferritinophagy may be a potential molecular target for cancer. © 2021 Bioelectromagnetics Society.

12.
Cell Signal ; 84: 110024, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33901579

RESUMO

Iron is an essential element for crucial biological function; whereas excess iron sedimentation impairs the main functions of tissues or organs. Cumulative researches have shown that the disturbances in iron metabolism, especially iron overload is closely concatenating with bone loss. Nevertheless, the specific process of iron overload-induced apoptosis in osteoblasts has not been thoroughly studied. In this study, our purpose is to elucidate the mechanism of osteoblast apoptosis induced by iron overload via the MC3T3-E1 cell line. Ferric ammonium citrate (FAC) was utilized to simulate iron overload conditions in vitro. These results showed that treatment with FAC dose-dependently induced the apoptosis of MC3T3-E1 cells at 48 h, dysfunction of iron metabolism, and increased intracellular reactive oxygen species (ROS) levels. Following, FAC does-dependently caused the calcium dyshomeostasis, decreased the calcium concentration in endoplasmic reticulum (ER), but increased the crosstalk between ER and mitochondria, and calcium concentration in the mitochondria. Moreover, FAC dose-dependently decreased mitochondrial membrane potential (MMP) and enhanced the expression of apoptosis related proteins (Bax, Cyto-C and C-caspase3). We furthermore revealed that FAC treatment activated the ER-mediated cell apoptosis via p-eIF2α/ATF4/CHOP pathway in MC3T3-E1 osteoblasts cells. In addition, pretreatment with the N-acetylcysteine (NAC) or Tauroursodeoxycholate Sodium (TUDC) attenuated cell apoptosis, ROS levels, mitochondria fragmentation and ER stress-related protein expression, and recovered the protein expression related to iron metabolism. In conclusion, our finding suggested that iron overload induced apoptosis via eliciting ER stress, which resulted in mitochondrial dysfunction and activated p-eIF2α/ATF4/CHOP pathway.

13.
Int J Radiat Biol ; 97(5): 746-754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720796

RESUMO

PURPOSE: Bone loss is one of the most serious medical problem associated with prolonged weightlessness in long-term spaceflight mission. Skeletal reloading after prolonged spaceflight have indicated incomplete recovery of lost bone, which may lead to an increased risk of fractures in astronauts when returning to Earth. Substantial studies have revealed the capacity of static magnetic fields (SMFs) on treating various bone disorders, whereas it is unknown whether SMFs have the potential regulatory effects on bone quality in unloaded mice during unloading. This study was conducted to investigate the potential effects of whole-body SMF exposure with 0.2-0.4 T on the recovery of unloading-induced bone loss. MATERIALS AND METHODS: Eight-week-old male C57BL/6J mice were subjected to hindlimb unloading (HLU) for 4 weeks, following the mice were reloaded for 4 weeks under geomagnetic field (GMF) and SMF of 0.2-0.4 T. Bone quality indexes, including bone mineral density (BMD) and bone mineral content (BMC), bone microarchitecture, and bone mechanical properties were examined by the measurement of dual energy X-ray absorptiometry (DEXA), micro-computed tomography (Micro-CT), and 3-point bending. Bone turnover was evaluated by bone histomorphometric and serum biochemical assay. RESULTS: We found that SMF exposure for 4 weeks significantly promoted the recovery in HLU-induced decrease of BMD and BMC, deterioration of bone microarchitecture, and reduction of bone strength. The results from bone turnover determination revealed that SMF exposure for 4 weeks induced lower osteoclast number of trabecular bone and serum TRAP-5b levels in reloaded mice, whereas SMF showed no significant alteration in skeletal osteoblast number and serum osteocalcin levels. CONCLUSIONS: Together, our findings suggest that SMF of 0.2-0.4 T facilitated the recovery of unloading-induced bone loss by inhibiting the increase of bone resorption in reloaded mice, and indicate that SMF might become a promising biophysical countermeasure for maintaining bone health in astronauts after landing.


Assuntos
Reabsorção Óssea/terapia , Elevação dos Membros Posteriores/efeitos adversos , Campos Magnéticos , Animais , Densidade Óssea , Reabsorção Óssea/diagnóstico por imagem , Reabsorção Óssea/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Voo Espacial , Microtomografia por Raio-X
14.
Bioelectromagnetics ; 42(3): 200-211, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33655538

RESUMO

Static magnetic field (SMF), with constant magnetic field strength and direction, has a long history of basic and clinical research in bone biology. Numerous studies demonstrate that exposure to moderate SMF (1 mT-1 T) can increase bone mass and bone density. However, few studies pay attention to the effects of high SMF (>1 T) on the skeletal system. To investigate the physiological effects of high SMF on bone, mice were exposed to 2-4 T SMF for 28 days. Bone microstructure and mechanical properties were examined. The activity of osteoblasts and osteoclasts involved in bone remodeling was evaluated in vivo and in vitro. Compared with the unexposed group, 2-4 T significantly improved the femoral microstructure and tibial mechanical properties. For bone remodeling in vivo, the number of osteoblasts and bone formation was increased, and the osteoclastic number was decreased by 2-4 T. Moreover, the expression of marker proteins in the femur and concentrations of biochemical indicators in serum involved in bone formation were elevated and bone resorption was reduced under 2-4 T SMF. In vitro, osteoblast differentiation was promoted, and the osteoclastic formation and bone resorption ability were inhibited by 2 T SMF. Overall, these results demonstrate that 2-4 T SMF improved bone microarchitecture and strength by stimulating bone formation and restraining bone resorption, and imply that high SMF might become a potential biophysical treatment modality for bone diseases with abnormal bone remodeling. Bioelectromagnetics. © 2021 Bioelectromagnetics Society.

15.
Commun Biol ; 4(1): 248, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627831

RESUMO

ßA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as ßA3 and ßA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that ßA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of ßA3/A1-crystallin in metabolism of retinal astrocytes. We found that ßA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but ßA3-crystallin does not. Loss of ßA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited ßA1-knockdown (KD) mice, but not in ßA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified ßA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced ßA1-crystallin and higher levels of PTP1B in the vitreous humor.


Assuntos
Astrócitos/enzimologia , Retinopatia Diabética/enzimologia , Metabolismo Energético , Glucose/metabolismo , Mitocôndrias/enzimologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Retina/enzimologia , Cadeia A de beta-Cristalina/metabolismo , Animais , Astrócitos/patologia , Estudos de Casos e Controles , Células Cultivadas , Cristalinas/genética , Cristalinas/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/patologia , Ligação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 1/genética , Ratos Sprague-Dawley , Retina/patologia , Cadeia A de beta-Cristalina/genética
16.
Cells ; 10(2)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530465

RESUMO

Bone-muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone-muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, Δ130-136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in Δ130-136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and Δ130-136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and Δ130-136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function; however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.


Assuntos
Osso e Ossos/metabolismo , Conexina 43/metabolismo , Músculos/metabolismo , Osteócitos/metabolismo , Animais , Osso e Ossos/efeitos dos fármacos , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Dinoprostona/farmacologia , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Camundongos Transgênicos , Contração Muscular/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculos/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Osteócitos/efeitos dos fármacos , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/metabolismo
17.
Cell Prolif ; 54(3): e12982, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33554390

RESUMO

Diabetes mellitus (DM) is a chronic metabolic disorder with various complications that poses a huge worldwide healthcare burden. Wounds in diabetes, especially diabetic foot ulcers (DFUs), are difficult to manage, often leading to prolonged wound repair and even amputation. Wound management in people with diabetes is an extremely clinical and social concern. Nowadays, physical interventions gain much attention and have been widely developed in the fields of tissue regeneration and wound healing. Magnetic fields (MFs)-based devices are translated into clinical practice for the treatment of bone diseases and neurodegenerative disorder. This review attempts to give insight into the mechanisms and applications of MFs in wound care, especially in improving the healing outcomes of diabetic wounds. First, we discuss the pathological conditions associated with chronic diabetic wounds. Next, the mechanisms involved in MFs' effects on wounds are explored. At last, studies and reports regarding the effects of MFs on diabetic wounds from both animal experiments and clinical trials are reviewed. MFs exhibit great potential in promoting wound healing and have been practised in the management of diabetic wounds. Further studies on the exact mechanism of MFs on diabetic wounds and the development of suitable MF-based devices could lead to their increased applications into clinical practice.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Campos Magnéticos , Cicatrização/efeitos dos fármacos , Experimentação Animal , Animais , Doença Crônica , Humanos
18.
Cells ; 10(1)2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450983

RESUMO

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis.


Assuntos
Desenvolvimento Muscular/genética , Músculo Esquelético/crescimento & desenvolvimento , Suínos/crescimento & desenvolvimento , Suínos/genética , Canais de Cátion TRPC/genética , Animais , Sequência de Bases , Diferenciação Celular , Fusão Celular , Linhagem Celular , Movimento Celular , Proliferação de Células , Haplótipos/genética , Hipertrofia , Camundongos , Mioblastos/citologia , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Canais de Cátion TRPC/metabolismo
19.
Biol Trace Elem Res ; 199(9): 3416-3422, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33411150

RESUMO

Relative stability of mineral elements in tissues is necessary for health. High static magnetic fields (HiSMFs) have been widely used in biomedical research and industry. However, the bioeffect of HiSMFs on animals is still unclear. In this study, we investigated the effects of HiSMF exposure on the levels of Mg, Fe, Zn, Ca, and Cu in the main organs of mice. The 8-week male C57BL/6 mice were treated by 2-4 T, 6-8 T, 10-12 T HiSMFs for 28 days. The mass fractions of Mg, Fe, Zn, Ca, and Cu in the liver, brain, kidney, and heart in mice were respectively measured by atomic absorption spectroscopy, and used to evaluate mineral element content in tissues. The 2-4 T HiSMF exposure has increased the Mg, Fe, and Ca content in the kidney, as well as the Zn content in the brain. The 6-8 T HiSMF exposure has increased the Zn level in the liver; Mg, Fe, and Ca levels in the kidney; and Fe level in the heart, while the Zn in the kidney, and Zn and Ca in the heart was decreased by 6-8 T HiSMF exposure. For the 10-12 T HiSMF exposure, the Mg in the kidney, the Fe in the liver and kidney, and Cu in the brain have been increased significantly. However, the Zn in the kidney and the Ca in the brain and the heart were reduced by 10-12 T HiSMF exposure. The HiSMF exposure for 28 days can alter the Mg, Fe, Zn, Ca, and Cu content in mice, and change with the different magnetic flux density of HiSMFs (2-4 T, 6-8 T, 10-12 T), elements, and organ types.


Assuntos
Minerais , Oligoelementos , Animais , Cobre , Rim , Fígado , Campos Magnéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL
20.
Autophagy ; 17(10): 3140-3159, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33404293

RESUMO

Retinal ganglion cell axons are heavily myelinated (98%) and myelin damage in the optic nerve (ON) severely affects vision. Understanding the molecular mechanism of oligodendrocyte progenitor cell (OPC) differentiation into mature oligodendrocytes will be essential for developing new therapeutic approaches for ON demyelinating diseases. To this end, we developed a new method for isolation and culture of ON-derived oligodendrocyte lineage cells and used it to study OPC differentiation. A critical aspect of cellular differentiation is macroautophagy/autophagy, a catabolic process that allows for cell remodeling by degradation of excess or damaged cellular molecules and organelles. Knockdown of ATG9A and BECN1 (pro-autophagic proteins involved in the early stages of autophagosome formation) led to a significant reduction in proliferation and survival of OPCs. We also found that autophagy flux (a measure of autophagic degradation activity) is significantly increased during progression of oligodendrocyte differentiation. Additionally, we demonstrate a significant change in mitochondrial dynamics during oligodendrocyte differentiation, which is associated with a significant increase in programmed mitophagy (selective autophagic clearance of mitochondria). This process is mediated by the mitophagy receptor BNIP3L (BCL2/adenovirus E1B interacting protein 3-like). BNIP3L-mediated mitophagy plays a crucial role in the regulation of mitochondrial network formation, mitochondrial function and the viability of newly differentiated oligodendrocytes. Our studies provide novel evidence that proper mitochondrial dynamics is required for establishment of functional mitochondria in mature oligodendrocytes. These findings are significant because targeting BNIP3L-mediated programmed mitophagy may provide a novel therapeutic approach for stimulating myelin repair in ON demyelinating diseases.Abbreviations: A2B5: a surface antigen of oligodendrocytes precursor cells, A2B5 clone 105; ACTB: actin, beta; APC: an antibody to label mature oligodendrocytes, anti-adenomatous polyposis coli clone CC1; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG9A: autophagy related 9A; AU: arbitrary units; BafA1: bafilomycin A1; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, autophagy related; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CASP3: caspase 3; CNP: 2',3'-cyclic nucleotide 3'-phosphodiesterase; Ctl: control; COX8: cytochrome c oxidase subunit; CSPG4/NG2: chondroitin sulfate proteoglycan 4; DAPI: 4'6-diamino-2-phenylindole; DNM1L: dynamin 1-like; EGFP: enhanced green fluorescent protein; FACS: fluorescence-activated cell sorting; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary growth factor; GFP: green fluorescent protein; HsESC: human embryonic stem cell; IEM: immunoelectron microscopy; LAMP1: lysosomal-associated membrane protein 1; LC3B: microtubule-associated protein 1 light chain 3; MBP: myelin basic protein; MFN2: mitofusin 2; Mito-Keima: mitochondria-targeted monomeric keima-red; Mito-GFP: mitochondria-green fluorescent protein; Mito-RFP: mitochondria-red fluorescent protein; MitoSOX: red mitochondrial superoxide probe; MKI67: antigen identified by monoclonal antibody Ki 67; MMP: mitochondrial membrane potential; O4: oligodendrocyte marker O4; OLIG2: oligodendrocyte transcription factor 2; ON: optic nerve; OPA1: OPA1, mitochondrial dynamin like GTPase; OPC: oligodendrocyte progenitor cell; PDL: poly-D-lysine; PINK1: PTEN induced putative kinase 1; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; RFP: red fluorescent protein; RGC: retinal ganglion cell; ROS: reactive oxygen species; RT-PCR: real time polymerase chain reaction; SEM: standard error of the mean; SOD2: superoxide dismutase 2, mitochondrial; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TMRM: tetramethylrhodamine methyl ester; TOMM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin, beta; TUBB3: tubulin, beta 3 class III.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...