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1.
Neurochem Res ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319778

RESUMO

8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in-vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats' neurological functions. The rats' brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl's staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.

2.
Sci Rep ; 12(1): 18402, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319731

RESUMO

The aim of our study was to investigate waist circumference (WC) change and the risk of incident chronic obstructive pulmonary disease (COPD) among Chinese adults. A total of 8164 participants aged > 18 years who attended health examinations with repeat measurements of WC and lung function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)] from 2010 to 2019 were recruited. WC change was categorized as ≤ - 2.5%, - 2.5 to 2.5%, 2.5% to 5% and > 5% according to sex. Modified Poisson regression models were used to assess the association of WC gain and the risk of COPD. During the 10-year follow-up, a total of 917 COPD cases were identified. From baseline to follow-up, the mean FEV1 decreased from 3.20 to 2.79L among male participants and 2.28-1.95L among female participants. Compared with participants who did not have abdominal obesity, at either, baseline or follow-up, participants with abdominal obesity of both sexes after the follow-up were associated with a greater risk of COPD regardless of abdominal obesity at baseline. The risk of incident COPD increased 19% among male participants (RR = 1.19, 95%CI = 1.04-1.48) and 14% among female participants (RR = 1.14, 95%CI = 1.01-1.40) when WC gain increased > 5% during the 10-year follow-up. The COPD risk decreased 18% among male participants with a WC change ≤ - 2.5% (RR = 0.82, 95%CI = 0.67-0.99). The risk of incident COPD was positively associated with increasing WC among Chinese adults of both sexes.


Assuntos
Obesidade Abdominal , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Masculino , Feminino , Circunferência da Cintura , Estudos de Coortes , Fatores de Risco , Volume Expiratório Forçado , China , Índice de Massa Corporal
3.
Artigo em Inglês | MEDLINE | ID: mdl-36367676

RESUMO

BACKGROUND: Rosacea is a chronic inflammatory skin disease with increased macrophage infiltration. However, the molecular mechanism remains unclear. OBJECTIVES: To determine the significance of macrophage infiltration, and correlation between Guanylate binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation. METHODS: Here we tested hypothesis that Guanylate binding protein 5 (GBP5) aggravate rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signaling pathway. We depleted macrophage by injecting clodronate-containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea-like skin inflammation when BALB/c mice was injected GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophages polarization, THP-1 cell was treated with GBP5 siRNA. RESULTS: Macrophage depletion ameliorated rosacea-like skin inflammation in mice, implying the important role of macrophages in the rosacea. Basing on transcriptome analysis, Guanylate binding protein 5 (GBP5) was identified as hub genes that was associated with the macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with the macrophage infiltration, the immunofluorescence analysis revealed the colocalization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea-like skin inflammation in the LL-37-induced mouse model and suppressed the expression of M1 signature genes such as IL-6, iNOS, and TNF-a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF-κB signaling pathways. CONCLUSIONS: Together, our study revealed the important role of macrophages in rosacea, and identified GBP5 as a key regulator of rosacea by inducing M1 macrophages polarization via NF-κB signaling pathways.

4.
Front Endocrinol (Lausanne) ; 13: 1042511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339447

RESUMO

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto's thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto's thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto's thyroiditis.


Assuntos
Doenças Autoimunes , Doença de Hashimoto , Tireoidite Autoimune , Camundongos , Animais , Tireoidite Autoimune/tratamento farmacológico , Células Th17/metabolismo , Células Th17/patologia , Leptina , Linfócitos T Reguladores , Receptores para Leptina , Doenças Autoimunes/metabolismo , Diferenciação Celular
5.
Hum Genet ; 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352239

RESUMO

Mitochondrial DNA (mtDNA) plays a critical role in oocyte maturation, fertilization, and early embryonic development. Defects in mtDNA may determine the alteration of the mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply, leading to impaired oocyte maturation, abnormal fertilization, and low embryonic developmental potential, ultimately leading to female infertility. This case-control study was established to investigate the correlation between mtDNA variations and early embryonic development defects. Peripheral blood was collected for next-generation sequencing from women who suffered the repeated failures of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) cycles due to early embryonic development defects as well as in-house healthy controls, and the sequencing results were statistically analyzed for all subjects. This study found that infertile women with early embryonic development defects carried more mtDNA variants, especially in the D-loop region, ATP6 gene, and CYTB gene. By univariate logistic regression analysis, 16 mtDNA variants were associated with an increased risk of early embryonic development defects (OR > 1, p < 0.05). Furthermore, we identified 16 potentially pathogenic mtDNA variants only in infertile cases. The data proved that mtDNA variations were associated with early embryonic development defects in infertile Chinese women.

6.
Sci Rep ; 12(1): 19497, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376427

RESUMO

This paper examined the effects of no treatment versus plasma treatment, and femtosecond laser irradiation as pre-annealing processes on indium zinc oxide (IZO) films and annealing at high temperatures. The plasma pre-annealed multilayer stacked IZO TFTs showed better electrical properties with mobility enhancement from 2.45 to 7.81 cm2/Vs, but exhibited diminished on-off current ratio (Ion/Ioff). The IZO thin-film transistor (TFT) prepared with femtosecond laser pre-annealing with low pulse energy generation (power of 3 W at 700 nm wavelength) for 100 s has also exhibited significantly improved electrical performance, the saturation mobility increased to 4.91 cm2/Vs, the Ion/Ioff ratio was enhanced from 4.5 × 105 to 2.1 × 106, the threshold voltage improved from - 1.44 to - 0.25 V, and the subthreshold swing was reduced from 1.21 to 0.61 V/dec. In conclusion, IZO TFTs with improved performance can be prepared using a femtosecond laser pre-annealing process, which has great potential for fabricating low-cost, high-performance devices.

7.
Infect Dis Poverty ; 11(1): 109, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273213

RESUMO

BACKGROUND: Zoonoses are public health threats that cause severe damage worldwide. Zoonoses constitute a key indicator of One Health (OH) and the OH approach is being applied for zoonosis control programmes of zoonotic diseases. In a very recent study, we developed an evaluation system for OH performance through the global OH index (GOHI). This study applied the GOHI to evaluate OH performance for zoonoses in sub-Saharan Africa. METHODS: The framework for the OH index on zoonoses (OHIZ) was constructed including five indicators, 15 subindicators and 28 datasets. Publicly available data were referenced to generate the OHIZ database which included both qualitative and quantitative indicators for all sub-Sahara African countries (n = 48). The GOHI algorithm was used to estimate scores for OHIZ. Indicator weights were calculated by adopting the fuzzy analytical hierarchy process. RESULTS: Overall, five indicators associated with weights were generated as follows: source of infection (23.70%), route of transmission (25.31%), targeted population (19.09%), capacity building (16.77%), and outcomes/case studies (15.13%). Following the indicators, a total of 37 sub-Sahara African countries aligned with OHIZ validation, while 11 territories were excluded for unfit or missing data. The OHIZ average score of sub-Saharan Africa was estimated at 53.67/100. The highest score was 71.99 from South Africa, while the lowest score was 40.51 from Benin. It is also worth mentioning that Sub-Sahara African countries had high performance in many subindicators associated with zoonoses, e.g., surveillance and response, vector and reservoir interventions, and natural protected areas, which suggests that this region had a certain capacity in control and prevention or responses to zoonotic events. CONCLUSIONS: This study reveals that it is possible to perform OH evaluation for zoonoses in sub-Saharan Africa by OHIZ. Findings from this study provide preliminary research information in advancing knowledge of the evidenced risks to strengthen strategies for effective control of zoonoses and to support the prevention of zoonotic events.


Assuntos
Saúde Única , Animais , Zoonoses/epidemiologia , Saúde Pública , Saúde Global , África do Sul
8.
Expert Opin Drug Deliv ; : 1-18, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36285632

RESUMO

INTRODUCTION: Brain diseases including brain tumor, Alzheimer's disease, Parkinson's disease, etc. are difficult to treat. The blood-brain barrier (BBB) is a major obstacle for drug delivery into the brain. Although nano-package and receptor-mediated delivery of nanomedicine markedly increases BBB penetration, it yet did not extensively improve clinical cure rate. Recently, brain extracellular space (ECS) and interstitial fluid (ISF) drainage in ECS have been found to determine whether a drug dissolved in ISF can reach its target cells. Notably, an increase in tortuosity of ECS associated with slower ISF drainage induced by the accumulated harmful substances, such as: amyloid-beta (Aß), α-synuclein, and metabolic wastes, causes drug delivery failure. AREAS COVERED: The methods of nano-package and receptor-mediated drug delivery and the penetration efficacy of nanomedicines across BBB and ECS are assessed. EXPERT OPINION: Invasive delivering drug via ECS and noninvasive near-infrared photo-sensitive nanomedicines may provide a promising benefit to patients with brain disease.

9.
Front Genet ; 13: 1015505, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263436

RESUMO

In this study, we used transcriptome and proteome technology to analyze molecular level changes in tissues of Coreius guichenoti cultured at high temperature (HT) and low temperature (LT). We also screened for specific anti-stress genes and proteins and evaluated the relationships between them. We identified 201,803 unigenes and 10,623 proteins. Compared with the normal temperature (NT), 408 genes and 1,204 proteins were up- or down-regulated in brain tissues, respectively, at HT, and the numbers were 8 and 149 at LT. In gill tissues, the numbers were 101 and 1,745 at HT and 27 and 511 at LT. In gill tissues at both temperatures, the degree of down-regulation (average, HT 204.67-fold, LT 443.13-fold) was much greater than that of up-regulation (average, HT 28.69-fold, LT 17.68-fold). The protein expression in brain (average, up 52.67-fold, down 13.54-fold) and gill (average, up 73.02-fold, down 12.92-fold) tissues increased more at HT than at LT. The protein expression in brain (up 3.77-fold, down 4.79-fold) tissues decreased more at LT than at HT, whereas the protein expression in gill (up 8.64-fold, down 4.35-fold) tissues was up-regulated more at LT than at HT. At HT, brain tissues were mainly enriched in pathways related to metabolism and DNA repair; at LT, they were mainly enriched in cancer-related pathways. At both temperatures, gill tissues were mainly enriched in pathways related to cell proliferation, apoptosis, immunity, and inflammation. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed more differentially expressed proteins in gill tissues than in brain tissues at HT and LT, and temperature stimulation led to the strengthening of metabolic pathways in both tissues. Of the 96 genes we identified as potentially being highly related to temperature stress (59 from transcriptome and 38 from proteome data), we detected heat shock protein 70 in both the transcriptome and proteome. Our results improved our understanding of the differential relationship between gene expression and protein expression in C. guichenoti. Identifying important temperature stress genes will help lay a foundation for cultivating C. guichenoti, and even other fish species, that are resistant to HT or LT.

10.
Plant Cell ; 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36222567

RESUMO

Fluctuations in nitrogen (N) availability influence protein and starch levels in maize (Zea mays) seeds, yet the underlying mechanism is not well understood. Here, we report that N limitation impacted the expression of many key genes in N and carbon (C) metabolism in the developing endosperm of maize. Notably, the promoter regions of those genes were enriched for P-box sequences, the binding motif of the transcription factor prolamin-box binding factor 1 (PBF1). Loss of PBF1 altered accumulation of starch and proteins in endosperm. Under different N conditions, PBF1 protein levels remained stable but PBF1 bound different sets of target genes, especially genes related to the biosynthesis and accumulation of N and C storage products. Upon N-starvation, the absence of PBF1 from the promoters of some zein genes coincided with their reduced expression, suggesting that PBF1 promotes zein accumulation in the endosperm. In addition, PBF1 repressed the expression of sugary1 (Su1) and starch branching enzyme 2b (Sbe2b) under normal N supply, suggesting that, under N-deficiency, PBF1 redirects the flow of C skeletons for zein toward the formation of C compounds. Overall, our study demonstrates that PBF1 modulates C and N metabolism during endosperm development in an N-dependent manner.

11.
Small ; : e2204271, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36228104

RESUMO

The surface properties of organic-inorganic hybrid perovskites can strongly affect the efficiency and stability of corresponding devices. Even though different surface passivation methods are developed, the microscopic structures of solution-processed perovskite film surfaces are not systematically studied. This study uses low-temperature scanning tunneling microscopy to study the organic-inorganic hybrid perovskite thin films, MA0.4 FA0.6 PbI3 and MAPbI3 , synthesized by the spin-coating method. Flat surface structures, atomic steps, and crystal grain boundaries are resolved at an atomic resolution. The surface imperfections are also characterized, as well as the dominant defects. Simulations on different types of iodine vacancy configurations are performed by density functional theory calculations. In addition, it is observed that the surface iodine lattice structure is unstable during scanning. Tip scanning can also cause the vertical migration of surface iodine ions. The measurements provide the direct visualizations of the surface imperfections of the solution-processed perovskite films. They are essential for understanding the surface-related optoelectronic effects and rationally designing more efficient surface passivation methods.

12.
Colloids Surf B Biointerfaces ; 220: 112881, 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36179610

RESUMO

Foam packaging with good thermal insulation and antibacterial properties is promising for cold chain delivery to strengthen food safety. This study reports a novel antibacterial foam with thermal insulation templated from bagasse nanocellulose complex particle-stabilised acrylate epoxy soybean oil (AESO) Pickering emulsions. Nanocellulose/nisin complex particles (N-CNFs) were prepared by loading positively charged nisin onto negatively charged cellulose nanofibrils via electrostatic interactions, that highly enhanced the stability of nanocellulose at the AESO/water interface and imparted the corresponding foam with good antibacterial properties. The results show that the porosity of the foam prepared with N-CNFs increased from 10.9% to 29.9% compared with that of the foam corresponding with bare nanocellulose; the thermal conductivity of the N-CNF foam decreased substantially from 0.431 W/m·K to 0.197 W/m·K. Moreover, the prepared foam exhibited good antibacterial activity, and its bacteriostatic rate against Listeria monocytogenes was 91.33%. The incorporation of antibacterial peptides into nanocellulose has enriched the study of the Pickering emulsion templating method for preparing multifunctional foam materials and is expected to broaden the application of nanocellulose in the field of food packaging.

13.
J Integr Plant Biol ; 64(11): 2033-2038, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36047457

RESUMO

Knowledge of the transcription factor binding landscape (TFBL) is necessary to analyze gene regulatory networks for important agronomic traits. However, a low-cost and high-throughput in vivo chromatin profiling method is still lacking in plants. Here, we developed a transient and simplified cleavage under targets and tagmentation (tsCUT&Tag) that combines transient expression of transcription factor proteins in protoplasts with a simplified CUT&Tag without nucleus extraction. Our tsCUT&Tag method provided higher data quality and signal resolution with lower sequencing depth compared with traditional ChIP-seq. Furthermore, we developed a strategy combining tsCUT&Tag with machine learning, which has great potential for profiling the TFBL across plant development.


Assuntos
Cromatina , Fatores de Transcrição , Sítios de Ligação , Análise Custo-Benefício , Ligação Proteica , Fatores de Transcrição/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala
14.
Science ; 378(6615): abo7923, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36074823

RESUMO

Translational regulation plays a critical role during the oocyte-to-embryo transition (OET) and zygotic genome activation (ZGA). Here, we integrated ultra-low-input ribosome profiling (Ribo-lite) with messenger RNA sequencing to co-profile the translatome and transcriptome in human oocytes and early embryos. Comparison with mouse counterparts identified widespread differentially translated gene functioning in epigenetic reprogramming, transposon defense, and small RNA biogenesis, in part driven by species-specific regulatory elements in 3' untranslated regions. Moreover, PRD-like homeobox transcription factors, including TPRXL, TPRX1, and TPRX2, are highly translated around ZGA. TPRX1/2/L knockdown leads to defective ZGA and preimplantation development. Ectopically expressed TPRXs bind and activate key ZGA genes in human embryonic stem cells. These data reveal the conservation and divergence of translation landscapes during OET and identify critical regulators of human ZGA.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Fatores de Transcrição , Transcriptoma , Zigoto , Regiões 3' não Traduzidas , Desenvolvimento Embrionário/genética , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zigoto/metabolismo
15.
J Sci Food Agric ; 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36168925

RESUMO

BACKGROUND: Barberry plants can be considered as useful additives and functional compounds in various industries, especially in the food industry. Berberine (BBR), the most important functional compound in the barberry roots, has recently been used to treat obesity, diabetes, and atherosclerosis. Gut microbiota and the intestinal barrier play an important role in the development of glucolipid metabolism disorders (GLMDs). However, the association of gut microbiota metabolism disorder and the intestinal barrier dysfunction effect of BBR in GLMDs remains elusive. RESULTS: The results showed that administration of BBR could increase the number of colonic glands and goblet cell mucus secretion, improve the intestinal barrier function, and reduce the serum glycolipid level in GLMD hamsters. Interestingly, BBR was metabolized into 12 metabolites by gut microbiota, and the main metabolic pathways were oxidation, demethylation, and hydrogenation. In addition, BBR significantly improved the species diversity and uniformity of gut microbiota and promoted the proliferation of beneficial microbiota. Furthermore, the levels of tryptophan metabolites, such as indole, indole-3-acetamide, indole-3-acetaldehyde, indole-3-pyruvic acid, and indole-3-acetic acid were significantly altered by BBR. Both the intestinal tight junction proteins and intestinal immune factors were altered by BBR. CONCLUSION: BBR could alleviate intestinal barrier dysfunction of GLMDs by modulating gut microbiota and gut-microbiota-related tryptophan metabolites, which may be one of the pharmacological mechanisms for the treatment of GLMDs. © 2022 Society of Chemical Industry.

16.
Eur J Cancer ; 175: 125-135, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36113242

RESUMO

BACKGROUND: A phase 1a first-in-human study evaluated the safety/tolerability, preliminary antitumour activity and pharmacokinetics of the oral MEK1/2 inhibitor FCN-159 in Chinese patients with advanced, NRAS-mutant melanoma. PATIENTS AND METHODS: Patients received a single FCN-159 dose at assigned levels, proceeding to continuous dosing (once daily [QD] for 28-day cycles) if no dose-limiting toxicities (DLTs) occurred within the next 3 days. Dose escalation was initiated after review of data for the previous dose level. The primary end-point was incidence of DLTs after the first dose. RESULTS: Thirty-three patients were enrolled across nine FCN-159 dose groups (0.2-15 mg QD). One DLT occurred: grade 3 folliculitis in the 15-mg group. There was one grade >3 treatment-emergent adverse event (TEAE), death of unknown aetiology (not FCN-159 related). The most common FCN-159-related TEAE was rash (36.4%), and the incidence of grade ≥3 FCN-159-related TEAEs was 15.2%. Antitumour activity at QD doses <6 mg was limited; therefore, efficacy data are presented only for doses ≥6 mg (n = 21). The objective response and clinical benefit rates were 19.0% (four partial responses) and 52.4%, respectively. Median (95% confidence interval) duration of response and progression-free survival were 4.8 months (2.8-not reached) and 3.8 months (1.8-5.6), respectively. FCN-159 exposure increased dose-proportionately; geometric mean terminal half-life was 29.9-56.9 h. CONCLUSIONS: FCN-159 was well tolerated and demonstrated promising antitumour activity at doses ≥6 mg QD in patients with advanced, NRAS-mutant melanoma. The recommended phase 2 dose was 12 mg QD. GOV IDENTIFIER: NCT03932253. https://clinicaltrials.gov/ct2/show/NCT03932253.


Assuntos
Antineoplásicos , Melanoma , Neoplasias , Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , GTP Fosfo-Hidrolases/genética , Humanos , Dose Máxima Tolerável , Melanoma/induzido quimicamente , Melanoma/tratamento farmacológico , Melanoma/genética , Proteínas de Membrana , Neoplasias/tratamento farmacológico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos
17.
Phytother Res ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086852

RESUMO

Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF-ß1)-mediated EMT process. Meanwhile, the anticarcinogenic effects of Resv were abolished by the autophagy blocker 3-methyladenine (3-MA) or Beclin 1 small interfering RNA. Moreover, Resv upregulated autophagy-related genes and protein levels and induced the formation of autophagosomes in 4T1 breast cancer cells and xenograft mice, suggesting that autophagy was involved in the anticarcinogenic activities of Resv in both models. In addition, Resv-induced autophagy by increasing the expression of SIRT3 and phosphorylated AMPK. SIRT3 knockdown reduced AMPK phosphorylation and autophagy-related proteins levels, and suppressed the anticancer effects of Resv, demonstrating that the inhibitory effects of Resv on tumor progression were mediated via the SIRT3/AMPK/autophagy pathway. Taken together, our study provided novel insight into the anticancer effects of Resv and revealed that targeting the SIRT3/AMPK/autophagy pathway can serve as a new therapeutic target against breast cancer.

18.
Nat Commun ; 13(1): 5426, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109528

RESUMO

Optical computing with integrated photonics brings a pivotal paradigm shift to data-intensive computing technologies. However, the scaling of on-chip photonic architectures using spatially distributed schemes faces the challenge imposed by the fundamental limit of integration density. Synthetic dimensions of light offer the opportunity to extend the length of operand vectors within a single photonic component. Here, we show that large-scale, complex-valued matrix-vector multiplications on synthetic frequency lattices can be performed using an ultra-efficient, silicon-based nanophotonic cavity acousto-optic modulator. By harnessing the resonantly enhanced strong electro-optomechanical coupling, we achieve, in a single such modulator, the full-range phase-coherent frequency conversions across the entire synthetic lattice, which constitute a fully connected linear computing layer. Our demonstrations open up the route toward the experimental realizations of frequency-domain integrated optical computing systems simultaneously featuring very large-scale data processing and small device footprints.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36170583

RESUMO

Electric/magnetic material or field is a promising strategy for bone regeneration. The aim of this systematic review and network meta-analysis was to analyze the evidence regarding the efficacy of electric and magnetic intervention for bone regeneration and provide directions for further research. A comprehensive search was performed to identify the rats/rabbits/mice research that involved the electric/magnetic treatment with quantitative radiographic assessment of bone formation. Network meta-analyses were also conducted to assess different interventions and outcomes for osteogenesis. In total, there were 51 papers included in the systematic review and 19 papers in the network meta-analyses. The majority used micro-CT bone volume/tissue volume (BV/TV) to evaluate outcomes in rats. Results showed that placing electric/magnetic materials in situ had more prominent effects than the electric/magnetic field on bone regeneration. For all species, electrical materials with zeta potential of -53 mV proved to be the most effective in increasing BV (MD: 4.20 mm3, 95% CI: [1.72, 6.68]) and BMD (MD: 312 mg/cm3, 95% CI: [172.43, 451.57]). Magnetic materials with external magnetic fields topped in BV/TV (MD: 43%, 95% CI: [36.04, 49.96]). It also led in Tb.N (MD: 2.00 mm-1, 95% CI: [1.45, 2.55]), Tb.Th (MD: 61.00 µm, 95% CI: [44.31, 77.69]) and Tb.Sp (MD: -0.40 mm, 95% CI: [-0.56, -0.24]) on the condition of lacking electric materials. Biomaterials implantation is the most effective method for stimulating osteogenesis in rats, especially in electrical materials with negative charge. The combination of diverse interventions shows promising effects but needs further research, so does the underlying mechanism.

20.
Front Endocrinol (Lausanne) ; 13: 945609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060969

RESUMO

Objective: To observe the effect of metformin (MET) monotherapy versus MET plus liraglutide (LIRA) on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome (PCOS). Methods: Sixty overweight patients with PCOS were recruited from January 2021 to January 2022 in Shengjing Hospital of China Medical University and were randomly assigned to the MET or combination (COM) group to receive 12 weeks of MET monotherapy or MET plus LIRA therapy. Anthropometric measurements, menstrual cycle changes, gonadal profiles, and oral glucose tolerance tests (OGTT) were conducted at baseline and after the 12-week treatment. Results: Fifty-two subjects completed the trial while eight were lost during the follow-up. Both MET and COM improved menstrual cycles, anthropometric parameters, and glucose metabolism after the 12-week treatment; however, there was no statistical difference between the two groups. MET plus LIRA therapy improved hyperandrogenemia, including TT (total testosterone), SHBG (sex hormone binding globulin) and FAI (free androgen index), whereas MET monotherapy only improved SHBG and FAI when compared with baseline. Furthermore, both MET monotherapy and MET plus LIRA therapy improved E2 (estradiol) while only MET plus LIRA therapy improved LH (luteinizing hormone), FSH (follicle stimulating hormone) and Prog (progesterone) more effectively than baseline. Additionally, MET plus LIRA therapy may improve TT, SHBG, FAI, LH and Prog more effectively than MET monotherapy; however, there were no significant differences on E2, FSH and LH/FSH between the two groups. Conclusions: In overweight patients with PCOS, both MET monotherapy and MET plus LIRA therapy improved glucose metabolism and relieved insulin resistance (IR). Additionally, MET plus LIRA therapy was more effective than MET monotherapy in improving reproductive abnormalities and hyperandrogenemia, potentially by modulating the hypothalamic-pituitary-ovarian axis.


Assuntos
Metformina , Síndrome do Ovário Policístico , Feminino , Hormônio Foliculoestimulante/metabolismo , Glucose , Humanos , Liraglutida/uso terapêutico , Metaboloma , Metformina/uso terapêutico , Obesidade/metabolismo , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo
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