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1.
Artigo em Inglês | MEDLINE | ID: mdl-39318013

RESUMO

OBJECTIVE: Cinnamomi cortex (CC), a traditional Chinese herbal medicine, exhibits antidiabetic properties, yet the underlying mechanisms are not fully understood. Our study combined network pharmacology, molecular docking, and experimental validation to elucidate the antidiabetic mechanisms of CC. METHODS: Active components of CC and their potential antidiabetic targets were identified through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database. Molecular docking with core targets was performed using Autodock Vina. The efficacy of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the T2DM mouse. RESULTS: Eleven active components and sixty-six potential antidiabetic targets of CC were identified. The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects. CONCLUSION: CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated inflammation, providing a multi-pathway therapeutic approach.

2.
Bioinformatics ; 40(4)2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38498847

RESUMO

MOTIVATION: Proteoform identification is an important problem in proteomics. The main task is to find a modified protein that best fits the input spectrum. To overcome the combinatorial explosion of possible proteoforms, the proteoform mass graph and spectrum mass graph are used to represent the protein database and the spectrum, respectively. The problem becomes finding an optimal alignment between the proteoform mass graph and the spectrum mass graph. Peak error correction is an important issue for computing an optimal alignment between the two input mass graphs. RESULTS: We propose a faster algorithm for the error correction alignment of spectrum mass graph and proteoform mass graph problem and produce a program package TopMGFast. The newly designed algorithms require less space and running time so that we are able to compute global optimal alignments for the two input mass graphs in a reasonable time. For the local alignment version, experiments show that the running time of the new algorithm is reduced by 2.5 times. For the global alignment version, experiments show that the maximum mass errors between any pair of matched nodes in the alignments obtained by our method are within a small range as designed, while the alignments produced by the state-of-the-art method, TopMG, have very large maximum mass errors for many cases. The obtained alignment sizes are roughly the same for both TopMG and TopMGFast. Of course, TopMGFast needs more running time than TopMG. Therefore, our new algorithm can obtain more reliable global alignments within a reasonable time. This is the first time that global optimal error correction alignments can be obtained using real datasets. AVAILABILITY AND IMPLEMENTATION: The source code of the algorithm is available at https://github.com/Zeirdo/TopMGFast.


Assuntos
Processamento de Proteína Pós-Traducional , Proteoma , Proteoma/metabolismo , Algoritmos , Espectrometria de Massas em Tandem , Software
3.
Artigo em Inglês | MEDLINE | ID: mdl-38194376

RESUMO

Rearrangement sorting problems impact profoundly in measuring genome similarities and tracing historic scenarios of species. However, recent studies on genome rearrangement mechanisms disclosed a statistically significant evidence, repeats are situated at the ends of rearrangement relevant segments and stay unchanged before and after rearrangements.To reflect the principle behind this evidence, we propose flanked block-interchange, an operation on strings that exchanges two substrings flanked by identical left and right symbols in a string. The flanked block-interchange distance problem is formulated as finding a shortest sequence of flanked block-interchanges to transform a string into the other. We propose a sufficient and necessary condition for deciding whether two strings can be transformed into each other by flanked block-interchanges. This condition is linear time verifiable. Under this condition for two strings, we present a [Formula: see text]-approximation algorithm for the flanked block-interchange distance problem where each symbol occurs at most k times in a string and a polynomial algorithm for this problem where each symbol occurs at most twice in a string. We show that the problem of flanked block-interchange distance is NP-hard at last.


Assuntos
Rearranjo Gênico , Genoma , Algoritmos
4.
Front Pharmacol ; 14: 1089537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733502

RESUMO

Background: Exposure to ultraviolet B (UVB) radiation can damage the epidermis barrier function and eventually result in skin dryness. At present, little work is being devoted to skin dryness. Searching for active ingredients that can protect the skin against UVB-induced dryness will have scientific significance. Methods: Saussurea involucrata polysaccharide (SIP) has been shown to have significant antioxidant and anti-photodamage effects on the skin following UVB irradiation. To evaluate the effect of SIP on UVB-induced skin dryness ex vivo, SIP-containing hydrogel was applied in a mouse model following exposure to UVB and the levels of histopathological changes, DNA damage, inflammation, keratinocyte differentiation, lipid content were then evaluated. The underlying mechanisms of SIP to protect the cells against UVB induced-dryness were determined in HaCaT cells. Results: SIP was found to lower UVB-induced oxidative stress and DNA damage while increasing keratinocyte differentiation and lipid production. Western blot analysis of UVB-irradiated skin tissue revealed a significant increase in peroxisome proliferator-activated receptor-α (PPAR-α) levels, indicating that the underlying mechanism may be related to PPAR-α signaling pathway activation. Conclusions: By activating the PPAR-α pathway, SIP could alleviate UVB-induced oxidative stress and inhibit the inflammatory response, regulate proliferation and differentiation of keratinocytes, and mitigate lipid synthesis disorder. These findings could provide candidate active ingredients with relatively clear mechanistic actions for the development of skin sunscreen moisturizers.

5.
J Asian Nat Prod Res ; 25(8): 731-740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36448521

RESUMO

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

6.
IEEE/ACM Trans Comput Biol Bioinform ; 20(2): 1606-1612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35939453

RESUMO

Protein-protein interactions (PPIs) play an essential role for most of biological processes in cells. Many computational algorithms have thus been proposed to predict PPIs. However, most of them heavily rest on the biological information of proteins while ignoring the latent structural features of proteins presented in a PPI network. In this paper, we propose an efficient network-based prediction algorithm, namely PPISB, based on a mixed membership stochastic blockmodel. By simulating the generative process of a PPI network, PPISB is able to capture the latent community structures. The inference procedure adopted by PPISB further optimizes the membership distributions of proteins over different complexes. After that, a distance measure is designed to compute the similarity between two proteins in terms of their likelihoods of being in the same complex, thus verifying whether they interact with each other or not. To evaluate the performance of PPISB, a series of extensive experiments have been conducted with five PPI networks collected from different species and the results demonstrate that PPISB has a promising performance when applied to predict PPIs in terms of several evaluation metrics. Hence, we reason that PPISB is preferred over state-of-the-art network-based prediction algorithms especially for predicting potential PPIs.


Assuntos
Algoritmos , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Proteínas/metabolismo , Probabilidade , Biologia Computacional/métodos , Mapas de Interação de Proteínas
7.
J Nat Prod ; 85(12): 2789-2795, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36480660

RESUMO

Four new bisanthraquinones, dothideomins A-D (1-4), were identified from Dothideomycetes sp. BMC-101, an endophytic fungus isolated from Magnolia grandiflora L. leaves. Their chemical structures were established by NMR analysis, single-crystal X-ray crystallography, and ECD analysis. Dothideomins A-D (1-4) were characterized by an unusual 6/6/6/5/6/3/6/6 octocyclic scaffold (1 and 2) and a 6/6/6/5/6/6/6 heptacyclic scaffold (3 and 4), respectively. All compounds, especially 1 and 3, exhibited potent antibacterial activity with MIC values ranging from 0.4 to 0.8 µg/mL.


Assuntos
Antibacterianos , Ascomicetos , Antibacterianos/química , Ascomicetos/química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Estrutura Molecular
8.
Front Pharmacol ; 13: 1036013, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386220

RESUMO

The integrity of skin tissue structure and function plays an important role in maintaining skin rejuvenation. Ultraviolet (UV) radiation is the main environmental factor that causes skin aging through photodamage of the skin tissue. Cryptotanshinone (CTS), an active ingredient mianly derived from the Salvia plants of Lamiaceae, has many pharmacological effects, such as anti-inflammatory, antioxidant, and anti-tumor effects. In this study, we showed that CTS could ameliorate the photodamage induced by UV radiation in epidermal keratinocytes (HaCaT) and dermal fibroblasts (HFF-1) when applied to the cells before exposure to the radiation, effectively delaying the aging of the cells. CTS exerted its antiaging effect by reducing the level of reactive oxygen species (ROS) in the cells, attenuating DNA damage, activating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway, and reduced mitochondrial dysfunction as well as inhibiting apoptosis. Further, CTS could promote mitochondrial biosynthesis in skin cells by activating the AMP-activated protein kinase (AMPK)/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) signaling pathway. These findings demonstrated the protective effects of CTS against UV radiation-induced skin photoaging and provided a theoretical and experimental basis for the application of CTS as an anti-photodamage and anti-aging agent for the skin.

9.
Ann Transl Med ; 10(20): 1104, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388783

RESUMO

Background: The inhibition of fibroblast growth factor 18 (FGF18) promotes the transition of hair follicles (HFs) from the telogen phase to the anagen phase. Cucurbitacin has been shown to have a good effect in promoting hair cell growth. This study explored the potential effect of cucurbitacin on hair growth and its effect on FGF18 expression in mice. Methods: Male C57BL/6J mice were randomly divided into the following two groups: (I) the vehicle group; and (II) the cucurbitacin group. Matrix cream and cucurbitacin cream were applied to the depilated skin on the back of the vehicle group mice and the cucurbitacin group mice, respectively. On days 3, 6, 9, 12, 15, and 18, the hair growth in the depilated dorsal skin of the mice was recorded with a digital camera and a HF detector, and the HF cycle status of the mice was observed by hematoxylin and eosin (H&E) staining. In addition, the level of FGF18 messenger ribonucleic acid (mRNA) in the dorsal skin was measured on days 15 and 18 by quantitative real-time polymerase chain reaction (qRT-PCR), while the level of FGF18 protein was measured by western blot and immunofluorescence staining. Results: The dorsal skin to which the cucurbitacin cream was applied began to darken on day 6 and grew hairs on day 9, which was 3 days earlier than the dorsal skin to which the matrix cream was applied. The H&E staining revealed a transition from the telogen phase to the anagen phase 3 days earlier for the cucurbitacin cream-treated skin than the matrix cream-treated skin. In addition, the skin treated with cucurbitacin cream also showed a significant decrease in FGF18 mRNA as seen by qRT-PCR, and reduced FGF18 protein levels as detected by western blot and immunofluorescence staining compared to the skin treated with matrix cream only. Conclusions: Cucurbitacin significantly reduced the levels of FGF18 mRNA and protein in the dorsal skin of mice to accelerate the HFs to enter the anagen phase earlier, thereby promoting the regeneration of hair. Thus, cucurbitacin can be considered a new and valuable agent for the development of anti-hair loss products.

10.
Environ Sci Pollut Res Int ; 29(43): 64267-64297, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35840830

RESUMO

Tunnels are widely used in high-grade roads, particularly in mountainous areas; however, tunnel fires often result in severe economic losses and casualties. The fire effluents produced from asphalt pavement have attracted significant research attention. The main objective of this study is to assimilate information on various aspects of bituminous mixture emissions during fires. In this study, the fume emissions of bitumen and bituminous mixtures during combustion are comprehensively reviewed and summarized. First, the test methods for fire effluents produced by bitumen and bituminous mixtures after combustion are summarized. Second, the factors influencing the fume concentration and composition are determined. In addition, different methods to reduce the emission of fire effluents are compared, particularly for the suppression of toxic gas emissions. Then, reasonable suggestions are proposed to reduce the damage caused by hazardous gases to humans and the environment. This review is beneficial for comprehensively understanding the fume emission behaviour and future research on the smoke suppression of highway tunnel asphalt pavements during fires.


Assuntos
Incêndios , Hidrocarbonetos , Gases , Humanos , Hidrocarbonetos/análise , Hidrocarbonetos/química , Fumaça/efeitos adversos , Fumaça/prevenção & controle
11.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35136947

RESUMO

In this paper, we study the problem for finding complex proteoforms from protein databases based on top-down tandem mass spectrum data. The main difficulty to solve the problem is to handle the combinatorial explosion of various alterations on a protein. To overcome the combinatorial explosion of various alterations on a protein, the problem has been formulated as the alignment problem of a proteoform mass graph (PMG) and a spectrum mass graph (SMG). The other important issue is to handle mass errors of peaks in the input spectrum. In previous methods, an error tolerance value is used to handle the mass differences between the matched consecutive nodes/peaks in PMG and SMG. However, such a way to handle mass error can not guarantee that the mass difference between any pairs of nodes in the alignment is approximately the same for both PMG and SMG. It may lead to large error accumulation if positive (or negative) errors occur consecutively for a large number of consecutive matched node pairs. The problem is severe so that some existing software packages include a step to further refine the alignments. In this paper, we propose a new model to handle the mass errors of peaks based on the formulation of the PMG and SMG. Note that the masses of sub-paths on the PMG are theoretical and suppose to be accurate. Our method allows each peak in the input spectrum to have a predefined error range. In the alignment of PMG and SMG, we need to give a correction of the mass for each matched peak within the predefined error range. After the correction, we impose that the mass between any two (not necessarily consecutive) matched nodes in the PMG is identical to that of the corresponding two matched peaks in the SMG. Intuitively, this kind of alignment is more accurate. We design an algorithm to find a maximum number of matched node and peak pairs in the two (PMG and SMG) mass graphs under the new constraint. The obtained alignment can show matched node and peak pairs as well as the corrected positions of peaks. The algorithm works well for moderate size input instances and takes very long time as well as huge size memory for large input size instances. Therefore, we propose an algorithm to do diagonal alignment. The diagonal alignment algorithm can solve large input size instances in reasonable time. Experiments show that our new algorithms can report alignments with much larger number of matched node pairs. The software package and test data sets are available at https://github.com/Zeirdo/TopMGRefine.


Assuntos
Algoritmos , Espectrometria de Massas em Tandem , Bases de Dados de Proteínas , Software , Espectrometria de Massas em Tandem/métodos
12.
Bioinformatics ; 38(8): 2333-2340, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35171986

RESUMO

MOTIVATION: Drawing peaks in a data window of an MS dataset happens at all time in MS data visualization applications. This asks to retrieve from an MS dataset some selected peaks in a data window whose image in a display window reflects the visual feature of all peaks in the data window. If an algorithm for this purpose is asked to output high-quality solutions in real time, then the most fundamental dependence of it is on the storage format of the MS dataset. RESULTS: We present mzMD, a new storage format of MS datasets and an algorithm to query this format of a storage system for a summary (a set of selected representative peaks) of a given data window. We propose a criterion Q-score to examine the quality of data window summaries. Experimental statistics on real MS datasets verified the high speed of mzMD in retrieving high-quality data window summaries. mzMD reported summaries of data windows whose Q-score outperforms those mzTree reported. The query speed of mzMD is the same as that of mzTree whereas its query speed stability is better than that of mzTree. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/yrm9837/mzMD-java. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Algoritmos , Software , Armazenamento e Recuperação da Informação , Visualização de Dados , Confiabilidade dos Dados
13.
J Med Genet ; 59(3): 230-236, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33397747

RESUMO

High-quality interpretation of BRCA1/2 variants plays a critical role in the clinical practice of precision medicine. However, a comprehensive system to evaluate the quality and accuracy of variant interpretation has yet to be established. This study investigates the performance of an interpretation system in evaluating the capacities of BRCA1/2 interpretation among distinct laboratories in China. The evaluation system is based on a reference database that contains 750 different variants in BRCA1/2 Evaluation was performed among 41 laboratories in China. We classified their performance into five levels. Only level A was considered qualified. This level allows for a 0.3% error rate for clinical decision-related misinterpretation; 26 of 41 laboratories (63%) met the qualified standard, while 7 laboratories were at levels D and E, which indicated egregious mistakes and systemic problems in variant interpretation. Due to strict quality demands, the interpretation of several variants was amended, which largely influenced the quality rate. The number of qualified laboratories would decrease from 26 to 17 if those incorrect recommended interpretations were not corrected. This evaluation system provides a potential approach for standardisation of variant interpretation and lowers the discordance of variant interpretation between different laboratories. A well-designed interpretation ability evaluation is essential to evaluate the interpretation level of laboratories before they provide service in real-world clinical settings.


Assuntos
Testes Genéticos , Laboratórios , Proteína BRCA1/genética , China , Variação Genética , Humanos
15.
J Bioinform Comput Biol ; 20(1): 2150033, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34895113

RESUMO

This paper deals with the problem of enumerating all minimum-cost LCA-reconciliations involving gene duplications and lateral gene transfers (LGTs) for a given species tree [Formula: see text] and a given gene tree [Formula: see text]. Previously, [Tofigh A, Hallett M, Lagergren J, Simultaneous identification of duplications and lateral gene transfers, IEEE/ACM Trans Comput Biol Bioinf 517-535, 2011.] gave a fixed-parameter algorithm for this problem that runs in [Formula: see text] time, where [Formula: see text] is the number of vertices in [Formula: see text], [Formula: see text] is the number of vertices in [Formula: see text], and [Formula: see text] is the minimum cost of an LCA-reconciliation between [Formula: see text] and [Formula: see text]. In this paper, by refining their algorithm, we obtain a new one for the same problem that finds and outputs the solutions in a compact form within [Formula: see text] time. In the most interesting case where [Formula: see text], our algorithm is [Formula: see text] times faster.


Assuntos
Evolução Molecular , Transferência Genética Horizontal , Algoritmos , Duplicação Gênica , Filogenia
16.
J Safety Res ; 79: 292-303, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34848010

RESUMO

INTRODUCTION: Driving under the influence (DUI) increases the probability of motor-vehicle collisions, especially for motorcycles with less protections. This study aimed to identify commonalities and differences between criminally DUI offenses (i.e., with a blood alcohol concentration (BAC) of 80 mg/dL or higher) committed by motorcyclists and car drivers. METHODS: A total of 10,457 motorcycle DUIs and 8,402 car DUIs were compared using a series of logistic regression models, using data extracted from the documents of adjudication decisions by the courts of Jiangsu, China. RESULTS: The results revealed that offenders from the high-BAC group (i.e., 200 mg/dL or higher) accounted for more than 20% of the total DUI offenses, and were more likely to be involved in a crash and punished with a longer detention. Motorcyclists had a higher likelihood of crash involvement, and were also more likely to be responsible for single-vehicle crashes associated with higher odds of injury sustained, compared to alcohol-impaired car drivers. In the verdict, motorcycle offenders were more likely to receive a less severe penalty. CONCLUSIONS: Interventions are clearly required to focus on reducing in the high-BAC group of offenders. For alcohol-impaired motorcyclists, their risks of crash and injury against BAC climb more steeply than the risks for car drivers. The factors including frequent occurrences, uncertainty of detection, and short-term sentences may weaken the deterrence effect of the criminalization of motorcycle DUI. Practical Applications: The traffic-related adjudication data support traffic safety analysis. Strategies such as combating motorcycle violations (e.g., unlicensed operators or driving unsafe vehicles), undertaking education and awareness campaigns, are expected for DUI prevention.


Assuntos
Concentração Alcoólica no Sangue , Dirigir sob a Influência , Acidentes de Trânsito , Automóveis , Humanos , Motocicletas
17.
Ann Transl Med ; 9(14): 1185, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34430626

RESUMO

BACKGROUND: Exposure to ultraviolet (UV) radiation (UVB and UVA) is the most well-known extrinsic factor that induces skin aging. Fucoidan has been shown to possess antiphotoaging effects against UV irradiation and can be used as an ingredient in the pharmaceutical industry. The present study evaluated the photoprotective effect of fucoidan purified from Undaria pinnatifida (UPF) on UV-induced skin photoaging and explored its potential molecular mechanism. METHODS: To evaluate the effect of UPF on UV-induced skin aging, HaCaT cells and HFF-1 cells were pretreated with or without UPF and then exposed to UVB and UVA radiation, respectively, and the levels of cellular senescence, reactive oxygen species (ROS) production and mitochondrial dysfunction were evaluated. The mitochondrial ROS (mROS) was stained through MitoSOX, and the confocal microscope was used to capture the images. For further exploration of AMPK/SIRT-1/PGC-1α signaling, western blot was employed. RESULTS: The results demonstrated that pretreatment of HaCaT and HFF-1 cells with UPF ameliorated cellular senescence, ROS and mROS overproduction, and mitochondrial dysfunction caused by UV exposure. This research also revealed that UPF could activate the AMPK/SIRT-1/PGC-1α signaling pathway to promote mitochondrial biogenesis. CONCLUSIONS: UPF can ameliorate UV-induced skin photoaging through inhibition of ROS production via the alleviation of mitochondrial dysfunction by regulating the SIRT-1/PGC-1α signaling pathway.

18.
Front Pharmacol ; 12: 666860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305588

RESUMO

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

19.
Ann Transl Med ; 9(12): 994, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277794

RESUMO

BACKGROUND: Fibroblast growth factor (FGF) 14 is a member of the FGF family that is mainly expressed in the central nervous system. FGF14 has a close association with the occurrence of neurodegenerative conditions; however, its significance in Alzheimer's disease (AD) has yet to be evaluated. Therefore, we sought to obtain a large amount of exogenous FGF14 protein and explore its effect in a cellular model of AD. METHODS: FGF14 protein was expressed in an Escherichia coli system using gene recombination technology. Purified protein was obtained through washing and renaturation of inclusion bodies combined with nickel column affinity chromatography. The AD model was established via Aß25-35-induced injury in PC12 cells. Changes in the levels of lactate dehydrogenase and malondialdehyde were detected, and the neuroprotective effect of recombinant human FGF14 (rhFGF14) was evaluated through double-fluorescence staining and flow cytometry apoptosis detection. For further exploration of rhFGF14-mediated regulation of mitogen-activated protein kinase (MAPK) signaling, western blot was employed. RESULTS: We successfully induced large amounts of insoluble rhFGF14. Following solubilization and refolding of the rhFGF14 from inclusion bodies, high purity rhFGF14 was purified by Nickel affinity column chromatography. The results showed that rhFGF14 alleviated Aß25-3-induced PC12 cell injury by inhibiting the phosphorylation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, thus suppressing the MAPK signaling pathway. CONCLUSIONS: FGF14 performed a neuroprotective role in our in vitro AD model via its inhibition of MAPK signaling, highlighting its potential as a therapeutic drug for neurodegenerative conditions.

20.
Int J Biol Macromol ; 185: 876-889, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34237364

RESUMO

The integrity of the epidermal barrier and the maintenance of barrier homeostasis depend on the dynamic balance between the proliferation and differentiation of keratinocytes. Calcium (Ca2+) plays a crucial role in maintaining a balance of these two processes as well as in the formation of an epidermal permeability barrier. In this study, we showed that topical application of oat ß-glucan (OG) could ameliorate epidermal hyperplasia and accelerate the recovery of the epidermal barrier by promoting epidermal differentiation. Mechanistic studies revealed a positive interaction between OG and the dectin-1 receptor, and this interaction could lead to an upregulated expression of the calcium-sensing receptor (CaSR) via activation of the downstream ERK and p38 pathways. This consequently increased the sensitivity of keratinocytes to extracellular Ca2+ under the condition of calcium loss following the disruption of the epidermal barrier, resulting in the maintenance of normal keratinocyte differentiation in the epidermis, and ultimately promoting the recovery of the epidermal barrier. These findings clearly demonstrated the healing effect of OG on a physically damaged epidermal barrier. Thus, OG could be considered a valuable component in the development of skin repair agents.


Assuntos
Avena/química , Queratinócitos/citologia , Lectinas Tipo C/metabolismo , Receptores de Detecção de Cálcio/metabolismo , beta-Glucanas/efeitos adversos , Animais , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células HaCaT , Humanos , Hiperplasia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Lectinas Tipo C/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Receptores de Detecção de Cálcio/genética , Regulação para Cima , beta-Glucanas/farmacologia
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