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1.
PLoS One ; 18(1): e0280112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598916

RESUMO

Ischemic stroke (IS) is one of the major global causes of death and disability. Because blood clots block the neural arteries provoking ischemia and hypoxia in the brain tissue, IS results in irreversible neurological damage. Available IS treatments are currently limited. Curcumin has gained attention for many beneficial effects after IS, including neuroprotective and anti-inflammatory; however, its precise mechanism of action should be further explored. With network pharmacology, molecular docking, and molecular dynamics (MD), this study aimed to comprehensively and systematically investigate the potential targets and molecular mechanisms of curcumin on IS. We screened 1096 IS-related genes, 234 potential targets of curcumin, and 97 intersection targets. KEGG and GO enrichment analyses were performed on these intersecting targets. The findings showed that the treatment of IS using curcumin is via influencing 177 potential signaling pathways (AGE-RAGE signaling pathway, p53 signaling pathway, necroptosis, etc.) and numerous biological processes (the regulation of neuronal death, inflammatory response, etc.), and the AGE-RAGE signaling pathway had the largest degree of enrichment, indicating that it may be the core pathway. We also constructed a protein-protein interaction network and a component-target-pathway network using network pharmacology. From these, five key targets were screened: NFKB1, TP53, AKT1, STAT3, and TNF. To predict the binding conformation and intermolecular affinities of the key targets and compounds, molecular docking was used, whose results indicated that curcumin exhibited strong binding activity to the key targets. Moreover, 100 ns MD simulations further confirmed the docking findings and showed that the curcumin-protein complex could be in a stable state. In conclusion, curcumin affects multiple targets and pathways to inhibit various important pathogenic mechanisms of IS, including oxidative stress, neuronal death, and inflammatory responses. This study offers fresh perspectives on the transformation of curcumin to clinical settings and the development of IS therapeutic agents.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , AVC Isquêmico , Humanos , Farmacologia em Rede , Curcumina/farmacologia , Curcumina/uso terapêutico , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular
2.
Int J Biol Macromol ; 231: 123285, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682649

RESUMO

In this study, heparin-like polysaccharides were successfully produced by sulfation of carboxymethylcellulose sodium, then a fully biobased bilayer composed of sulfated carboxymethylcellulose sodium (SCMC) and chitosan (CS) was composited on the surface of Poly (L-lactic acid) (PLA) through layer-by-layer (LBL) assembly for the potential blood-contact application such as bioresorbable vascular scaffold. The preliminary structure and bioactivity of SCMC with different degree of sulfation were investigated, and the SCMC with best performance was selected. The surface chemical compositions, morphologies and wettability of SCMC/CS multilayer-modified PLA films were researched by X-ray photoelectron spectrometer, scanning electron microscopy and water contact angle meter. A series of anticoagulation tests of SCMC/CS multilayer-modified PLA films were performed. In term of (SCMC/CS)15 multilayer-modified PLA film, the protein adsorption and plate adhesion decreased by 44.6 % and 71.5 %, respectively, the activated partial thromboplastin time prolonged by 11.9 times and thrombin time exceed 300 s, the contact activation and hemolysis rate significantly reduced compared with unmodified PLA film. Besides, this modified PLA films performed good cytocompatibility to L929 fibroblast cells, excellent anti-inflammatory and antibacterial abilities. In conclusion, the multifunctional SCMC/CS multilayer-modified PLA films with hemocompatibility, cytocompatibility, anti-inflammatory and antibacterial properties may have promising potential in future clinical applications.

3.
Phys Chem Chem Phys ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637033

RESUMO

This paper focuses on the development of a quantum mechanics/molecular mechanics method using the ABEEM polarizable force field (QM/MM(ABEEM) method) to investigate the excision reaction mechanism of damaged thymine. This method does not simply combine the QM method with the polarizable force field. A valence electronegativity piecewise function with the distance between atoms as a variable is introduced to describe the atomic partial charges, and changes greatly during the reaction process. At the same time, the charge transfer effect is treated using the condition of local charge conservation. Compared with the traditional QM/MM method, the QM/MM(ABEEM) method can more accurately simulate the polarization effect and charge transfer effect in the reaction process. Focusing on the controversial problems of the excision of damaged bases, six reaction pathways were designed for monofunctional and difunctional deglycosylation of neutral bases and protonated bases. The results show that the QM/MM(ABEEM) method accurately simulates the polarization effect, charge transfer effect, activation energy and other properties of the reaction process. The process in which the active residue Asp activates the nucleophile H2O to attack the protonated base is the preferred path. The average activation energy and free activation energy of the protonated base are 7.00-14.00 kcal mol-1 lower than that of the neutral base. The study in this paper is helpful to understand the mechanism of repair enzymes in repairing bases.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36588461

RESUMO

The Oak Ridge National Laboratory (ORNL) phantoms based on data of Caucasians have been widely used for fetal dosimetry. However, there are differences in body size during pregnancy among Taiwanese and Caucasians. In this study, the uterine dose conversion coefficients (DCCs) of Taiwanese pregnant women were evaluated to facilitate the use of it to estimate the possible uterine dose (usually regarded as fetal dose) of pregnant Taiwanese women during radiation practice or medical exposures. The uterine DCCs in this study were calculated based on the established Taiwanese pregnancy voxel phantoms, and were compared with the uterine DCCs of the International Commission on Radiological Protection. The applicability of evaluating uterine DCCs with different phantoms was also discussed. Results showed that if the ORNL phantoms are used to evaluate the uterine dose of Taiwanese pregnant women, the uterine dose may be underestimated. This study provides the uterine DCCs assessed with the Taiwanese pregnancy phantoms for future dose assessment of Taiwanese.

5.
World J Gastrointest Oncol ; 15(1): 90-101, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36684054

RESUMO

BACKGROUND: Heat-clearing and detoxifying drugs has protective effect on colorectal cancer (CRC). Given the complicated features of Traditional Chinese medicine formulas, network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases. AIM: To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724. METHODS: This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database. In addition, the CRC targets were obtained from Drugbank, TTD, DisGeNET and GeneCards databases. We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724. Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets. Core targets were selected by protein-protein interaction network and herb ingredient-target-disease network analysis. The functional and pathway of core targets were analysed by enrichment analysis. RESULTS: We found 174 active ingredients and 283 compound targets from JC724. 940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis. We constructed the network and found that the five core ingredients were quercetin, ß Beta sitosterol, wogonin, kaempferol and baicalein. The core JC724-CRC targets were CYP1A1, HMOX1, CXCL8, NQO1 and FOSL1. JC724 acts on multiple signaling pathways associated with CRC, including the Nrf2 signaling pathway, oxidative stress, and the IL-17 signaling pathway. CONCLUSION: In this study, we systematically analyzed the active ingredients, core targets and main mechanisms of JC724 in the treatment of CRC. This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

6.
Immunity ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36693372

RESUMO

Neuronal signals have emerged as pivotal regulators of group 2 innate lymphoid cells (ILC2s) that regulate tissue homeostasis and allergic inflammation. The molecular pathways underlying the neuronal regulation of ILC2 responses in lungs remain to be fully elucidated. Here, we found that the abundance of neurotransmitter dopamine was negatively correlated with circulating ILC2 numbers and positively associated with pulmonary function in humans. Dopamine potently suppressed lung ILC2 responses in a DRD1-receptor-dependent manner. Genetic deletion of Drd1 or local ablation of dopaminergic neurons augmented ILC2 responses and allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired the mitochondrial oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effect of dopamine. Local administration of dopamine alleviated allergen-induced ILC2 responses and airway inflammation. These findings demonstrate that dopamine represents an inhibitory regulator of ILC2 responses in allergic airway inflammation.

7.
Nat Commun ; 14(1): 317, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658135

RESUMO

Laminin polymerization is the major step in basement membranes assembly. Its failures cause laminin N-terminal domain lamininopathies including Pierson syndrome. We have employed cryo-electron microscopy to determine a 3.7 Å structure of the trimeric laminin polymer node containing α1, ß1 and γ1 subunits. The structure reveals the molecular basis of calcium-dependent formation of laminin lattice, and provides insights into polymerization defects manifesting in human disease.


Assuntos
Síndrome Nefrótica , Distúrbios Pupilares , Humanos , Laminina/química , Microscopia Crioeletrônica , Polimerização , Membrana Basal/química
8.
Eur J Med Res ; 28(1): 45, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694233

RESUMO

Acute kidney injury (AKI) is a common and serious complication of cardiac surgery and is associated with increased mortality and morbidity, accompanied by a substantial economic burden. The pathogenesis of cardiac surgery-associated acute kidney injury (CSA-AKI) is multifactorial and complex, with a variety of pathophysiological theories. In addition to the existing diagnostic criteria, the exploration and validation of biomarkers is the focus of research in the field of CSA-AKI diagnosis. Prevention remains the key to the management of CSA-AKI, and common strategies include maintenance of renal perfusion, individualized blood pressure targets, balanced fluid management, goal-directed oxygen delivery, and avoidance of nephrotoxins. This article reviews the pathogenesis, definition and diagnosis, and pharmacological and nonpharmacological prevention strategies of AKI in cardiac surgical patients.


Assuntos
Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Humanos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Rim , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Biomarcadores , Coração , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Risco
9.
J Clin Med ; 12(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36675380

RESUMO

Women with polycystic ovarian syndrome (PCOS) are more likely to have non-alcoholic fatty liver disease (NAFLD) than non-PCOS women; however, the exact mechanism underlying this trend is unknown. The receptor activator of NF-κB ligand (RANKL) is strongly involved in bone metabolism and has multiple functions. Recent studies suggest that RANKL is implicated in hepatic insulin resistance (IR), which is the highest risk factor for NAFLD. This study aimed to assess the role of RANKL in NAFLD in Chinese women with PCOS. A cross-sectional observational study was conducted on women newly diagnosed with PCOS, which included 146 patients with NAFLD and 142 patients without NAFLD. Sex hormones, glucose, insulin, and lipids were measured, and anthropometric data were collected. The concentration of serum total RANKL was measured using commercial ELISA kits. PCOS patients with NAFLD had a significantly higher mean age, body mass index (BMI), waist circumference (WC), and worsened metabolic profile than non-NAFLD subjects. The concentrations of high-sensitivity C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol increased with the RANKL tertile (p for trend = 0.023, 0.026, and 0.035, respectively). A significantly positive association was found between RANKL (per SD change) and the risks of NAFLD (OR = 1.545, 95% CI = 1.086-2.199) after adjusting for confounders, including demographic factors, metabolic markers, and sex hormones. Subgroup multivariate logistic analyses stratified by age, BMI, and WC showed the same tendency. In addition, the positive association between RANKL and NAFLD seemed more prominent in lean patients with a BMI < 24 kg/m2 (OR = 1.70, 95% CI = 1.06-2.75) when compared to overweight/obesity subjects. Therefore, this study suggests that RANKL is positively associated with the increased risk of NAFLD in Chinese women with PCOS, independent of metabolic and reproductive factors.

10.
Nutrients ; 15(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36678342

RESUMO

A major polymorphism in the fucosyltransferase2 (FUT2) gene influences risk of multiple gut diseases, but its impact on the microbiome of breastfed infants was unknown. In individuals with an active FUT2 enzyme ("secretors"), the intestinal mucosa is abundantly fucosylated, providing mutualist bacteria with a rich endogenous source of fucose. Non-secretors comprise approximately one-fifth of the population, and they lack the ability to create this enzyme. Similarly, maternal secretor status influences the abundance of a breastfeeding mother's fucosylated milk oligosaccharides. We compared the impact of maternal secretor status, measured by FUT2 genotype, and infant secretor status, measured by FUT2 genotype and phenotype, on early infant fecal microbiome samples collected from 2-month-old exclusively breastfed infants (n = 59). Infant secretor status (19% non-secretor, 25% low-secretor, and 56% full-secretor) was more strongly associated with the infant microbiome than it was with the maternal FUT2 genotype. Alpha diversity was greater in the full-secretors than in the low- or non-secretor infants (p = 0.049). Three distinct microbial enterotypes corresponded to infant secretor phenotype (p = 0.022) and to the dominance of Bifidobacterium breve, B. longum, or neither (p < 0.001). Infant secretor status was also associated with microbial metabolic capacity, specifically, bioenergetics pathways. We concluded that in exclusively breastfed infants, infant-but not maternal-secretor status is associated with infant microbial colonization and metabolic capacity.


Assuntos
Microbioma Gastrointestinal , Microbiota , Fucosiltransferases/genética , Genótipo , Leite Humano/metabolismo , Humanos , Feminino , Lactente
11.
Mol Brain ; 16(1): 14, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36694204

RESUMO

Status epilepticus (SE) in humans is characterized by prolonged convulsive seizures that are generalized and often difficult to control. The current antiseizure drugs (ASDs) aim to stop seizures quickly enough to prevent the SE-induced brain inflammation, injury, and long-term sequelae. However, sole reliance on acute therapies is imprudent because prompt treatment may not always be possible under certain circumstances. The pathophysiological mechanisms underlying the devastating consequences of SE are presumably associated with neuroinflammatory reactions, where prostaglandin E2 (PGE2) plays a pivotal role. As the terminal synthase for pathogenic PGE2, the microsomal prostaglandin E synthase-1 (mPGES-1) is rapidly and robustly induced by prolonged seizures. Congenital deletion of mPGES-1 in mice is neuroprotective and blunts gliosis following chemoconvulsant seizures, suggesting the feasibility of mPGES-1 as a potential antiepileptic target. Herein, we investigated the effects of a dual species mPGES-1 inhibitor in a mouse pilocarpine model of SE. Treatment with the mPGES-1 inhibitor in mice after SE that was terminated by diazepam, a fast-acting benzodiazepine, time-dependently abolished the SE-induced PGE2 within the brain. Its negligible effects on cyclooxygenases, the enzymes responsible for the initial step of PGE2 biosynthesis, validated its specificity to mPGES-1. Post-SE inhibition of mPGES-1 also blunted proinflammatory cytokines and reactive gliosis in the hippocampus and broadly prevented neuronal damage in a number of brain areas. Thus, pharmacological inhibition of mPGES-1 by small-molecule inhibitors might provide an adjunctive strategy that can be implemented hours after SE, together with first-line ASDs, to reduce SE-provoked brain inflammation and injury.


Assuntos
Encefalite , Estado Epiléptico , Humanos , Camundongos , Animais , Prostaglandina-E Sintases , Gliose/complicações , Gliose/tratamento farmacológico , Estado Epiléptico/tratamento farmacológico , Dinoprostona , Convulsões/tratamento farmacológico , Modelos Animais de Doenças
12.
Hortic Res ; 10(1): uhac228, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643758

RESUMO

Momordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.

13.
Oncol Lett ; 25(2): 53, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36644143

RESUMO

Breast cancer has the highest incidence rate among all cancer types worldwide, seriously threatening women's health. The present retrospective study explored differences in serum lipid contents in different breast cancer (BC) subcategories and their correlation with Ki-67 expression levels in patients with invasive BC with the aim of identifying novel diagnostic and prognostic indicators for personalized BC treatment. The study included 170 patients diagnosed with BC who were diagnosed with invasive BC by postoperative pathological examination. Data on patient age, body mass index and menopausal status were collected, in addition to estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and antigen Ki-67 expression levels and pathological tumor type. Preoperative circulating lipid levels, specifically the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and apolipoproteins A1 (ApoA1) and B (ApoB) were also obtained. Molecular subcategories of BC were grouped based on their immunohistochemistry. Differences in serum lipid levels between the groups were assessed, and correlations between serum lipid and Ki-67 expression levels were explored. While TC, LDL-C, HDL-C and ApoA1 levels differed significantly among molecular subcategories. TG and ApoB levels did not. Circulating TC and LDL-C levels were considerably higher in patients with triple-negative BC (TNBC) and HER2-positive [hormone receptor (HR)-negative] BC than in those with luminal A and B (HER2-negative) BC. Serum HDL-C levels were significantly diminished in the TNBC and HER2-positive (HR-negative) groups compared with the luminal A and B (HER2-negative) groups. ApoA1 levels were significantly reduced in cases of TNBC and HER2-positive (HR-negative) BC compared with luminal A and B BC. Ki-67 expression levels were positively correlated with circulating TC and LDL-C levels and inversely correlated with circulating HDL-C and ApoA1 levels but exhibited no correlation with serum ApoB and TG levels. The results indicate that elevated TC and LDL-C levels and diminished HDL-C and ApoA1 levels were high-risk factors in patients with TNBC and HER2-positive (HR-negative) BC, but not patients with luminal subcategories of BC. Abnormal serum lipid levels were correlated with Ki-67 expression levels, with elevated circulating TC and LDL-C levels and reduced circulating HDL-C and ApoA1 levels indicating a poor prognosis in patients with BC.

14.
Meat Sci ; 198: 109085, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36640716

RESUMO

To solve the problem of easy spoilage of chilled meat during storage, we fabricated a novel composite film using carboxymethyl chitosan (CMCS)/pullulan (Pul)/eugenol (E) by casting method. The results showed that the mechanical properties of the films were better when the CMCS/Pul ratio was 2.5/2.5. The Fourier transform infrared spectroscopy (FTIR) results showed that intermolecular hydrogen bonds were formed among E, CMCS, and Pul, which was consistent with the rheological test results. Scanning electron microscopic (SEM) images showed that eugenol was well dispersed in the CMCS/Pul matrix. The addition of eugenol significantly increased the antibacterial properties and antioxidant properties. Moreover, when 5% eugenol was added, the water vapor permeability (WVP) of the film reduced to 2.41 × 10-11 g/m·s·Pa. Finally, the freshness of the chilled meat wrapped with the eugenol-containing composite film was prolonged, thereby offering a potential alternative to synthetic materials.

15.
Phytomedicine ; 109: 154612, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610172

RESUMO

BACKGROUND: Macrophages are one of the major cell types in the immune system and are closely related to tumor development, which can be polarized into M1 type with anti-tumor activity or M2 type with pro-tumor activity. The infiltration of more macrophages into tumor predicts poorer prognosis due to their more exhibition of M2 phenotype under the influence of many factors in the tumor microenvironment (TME). Therefore, reverse of M2 macrophage polarization in TME is conducive to the suppression of tumor deterioration and understanding the influencing factors of macrophage polarization is helpful to provide new ideas for the subsequent targeting macrophages for tumor therapy. PURPOSE: This review summarizes the effects of TME on macrophage polarization and natural products against M2 macrophage polarization, which may provide some directions for tumor therapy. METHODS: The search of relevant literature was conducted using the PubMed, Science Direct, CNKI and Web of Science databases with the search terms "macrophage", "tumor microenvironment", "natural product" and "tumor". RESULTS: The mutual transformation of M1 and M2 phenotypes in macrophages is influenced by many factors. Tumor cells affect the polarization of macrophages by regulating the expression of genes and proteins and the secretion of cytokines. The expression of some genes or proteins in macrophages is also related to their own polarization. Many natural products can reverse M2 polarization of macrophages which has been summarized in this review. CONCLUSION: Regulation of macrophage polarization in TME can inhibit tumor development, and natural products have the potential to impede tumor development by regulating macrophage polarization.


Assuntos
Antineoplásicos , Produtos Biológicos , Neoplasias , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Macrófagos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Citocinas/metabolismo , Antineoplásicos/farmacologia , Microambiente Tumoral
16.
Theranostics ; 13(1): 40-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593951

RESUMO

Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Imunoterapia , Autofagia , Microambiente Tumoral
17.
Anim Genet ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596449

RESUMO

China has a long history of pig breeding and a number of local breeds. The Songliao Black pig, bred in China in 2009, shows high variation in backfat thickness and therefore is well-suited to fat deposition research. Fat deposition is a complex trait, and the underlying regulatory factors are not fully characterized. In this study, the molecular basis of fat deposition traits was evaluated by comparisons between three individuals with extremely high-backfat thickness and three with extremely low-backfat thickness selected from 53 gilts. Subcutaneous adipose tissues of the back were collected for strand-specific library RNA sequencing (RNA-seq) and small RNA-seq. We identified 13 184 mRNAs, 2046 long non-coding (lnc)RNAs, and 494 micro (mi)RNAs by high-throughput sequencing. Furthermore, we detected 150 differentially expressed mRNAs, 66 differentially expressed lncRNAs, and eight differentially expressed miRNAs. A functional enrichment analysis indicated that these genes are involved in multiple fat metabolism-related pathways, including positive regulation of fat cell differentiation, and fat digestion and absorption. We used various algorithms (miRanda, TargetScan, and RNAhybrid) to predict targeting relationships and constructed a competing endogenous RNA network containing seven lncRNAs, three miRNAs, and six mRNAs. All these genes were differentially expressed between the extremely high and low backfat thickness groups or enriched in pathways related to fat metabolism. Our results provide insight into the regulatory mechanisms by which non-coding RNAs and their target genes influence backfat deposition in pigs. Furthermore, our newly constructed competing endogenous RNA (lncRNA-miRNA-mRNA) network provides a basis for further exploration of fat deposition traits and non-coding RNA functions.

18.
Sci Rep ; 13(1): 387, 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617577

RESUMO

The purpose of this study was to investigate the association between time restricted feeding (TRF) and different areas of cognitive function in the elderly in Chinese communities. This study consisted of 1353 community-dwelling Chinese older adults aged 60 years and older in Chongming area, Shanghai (563 males; the mean age, 73.38 ± 6.16 years). Mild cognitive impairment (MCI) and six different cognitive domains was assessed by the Chinese-version of Mini Mental State Examination (MMSE). Recording the eating time of each meal through oral inquiry to calculate the time window between the first meal and the last meal of the average day. Participants with an eating time window duration of more than 10 h were then identified, as well as those with eating time restricted to less than 10 h (TRF). Our study found that TRF may be associated with a higher incidence rate of cognitive impairment. TRF only limited the eating time window and did not change the frequency of participants' dietary intake. We used a linear regression model to study the association of TRF with cognitive function. After adjusting for confounding variables, the results showed that TRF was related to MMSE score (P < 0.001), "Orientation to place" (P < 0.001) and "Attention/calculation" (P < 0.001) functions. Among Chinese older community-dwellers, TRF was associated with a higher prevalence of CI and negatively correlated with the "Orientation to place" and "attention/calculation" functions.


Assuntos
Disfunção Cognitiva , Idoso , Masculino , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Cognição
19.
Physiol Plant ; : e13853, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36628625

RESUMO

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 palys a role in regulating plant growth under abiotic conditions.

20.
Nanoscale ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36601712

RESUMO

Recently, chiral hybrid organic-inorganic perovskites (HOIPs) are drawing wide attention due to their intrinsic noncentrosymmetric structures which result in fascinating properties such as ferroelectronics and second-order nonlinear optics (NLO). However, previous research mainly focused on chiral lead-based halide perovskites ignoring that the toxic Pb element is harmful to humans and the environment. Herein, we successfully synthesized block-like (R-/S-NEA)2CuCl4 (NEA = 1-naphthylethylamine) and needle-like (R-/S-CYHEA)6Cu3Cl12 (CYHEA = 1-cyclohexylethylamine) single crystals, which crystallize in the Sohncke P21 and I2 space group, respectively. Each pair of chiral perovskite enantiomers shows mirror circular dichroism (CD) signals. The thin films show an efficient second harmonic generation (SHG) response and the NLO coefficients of (R-NEA)2CuCl4 and (R-CYHEA)6Cu3Cl12 are 11.74 and 3.04 pm V-1, respectively, under 920 nm excitation with Y-cut quartz as a reference, which shows that the chiral amine has a significant effect on the SHG behavior. The high SHG response of (R-NEA)2CuCl4 is perhaps due to the rigidity of the aromatic amine, which leads to highly asymmetrical space groups. Our results provide guidelines for designing and tuning the SHG response in chiral HOIPs.

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