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1.
Nature ; 592(7854): 428-432, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33790465

RESUMEN

Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone-which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans-regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.


Asunto(s)
Corticosterona/farmacología , Folículo Piloso/citología , Células Madre/citología , Células Madre/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Glándulas Suprarrenales/cirugía , Adrenalectomía , Animales , División Celular/efectos de los fármacos , Femenino , Folículo Piloso/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Psicológico/metabolismo , Estrés Psicológico/patología , Transcriptoma , Regulación hacia Arriba
2.
Chem Soc Rev ; 53(15): 7939-7959, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-38984392

RESUMEN

The ongoing evolution of two-dimensional (2D) material-based membranes has prompted the realization of mass separations at the 1-nm scale due to their well-defined selective nano- and subnanochannels. Strategic membrane functionalization is further found to be key to augmenting channel accuracy and efficiency in distinguishing ions, gases and molecules within this range and is thus trending as a research focus in energy-, resource-, environment- and pharmaceutical-related applications. In this review, we present the fundamentals underpinning functionalized 2D membranes in various separations, elucidating the critical "method-interaction-property" relationship. Starting with an introduction to various functionalization strategies, we focus our discussion on functionalization-induced channel-species interactions and reveal how they shape the transport- and operation-related features of the membrane in different scenarios. We also highlight the limitations and challenges of current functionalized 2D membranes and outline the necessary breakthroughs needed to apply them as reliable and high-performance separation units across industries in the future.

3.
J Lipid Res ; 65(9): 100623, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39154732

RESUMEN

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues and regulates obesity-related diseases; however, the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet-induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced the expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein one (UCP1), and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C-specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1, and mitochondrial complex expression. Our findings reveal that NPR-C deficiency enhances mitochondrial function and energy expenditure in white adipose tissue, contributing to improved metabolic health and resistance to obesity.

4.
Environ Sci Technol ; 58(15): 6835-6842, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38570313

RESUMEN

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.


Asunto(s)
Canales Iónicos , Metales , Nitritos , Elementos de Transición , Iones , Cationes Bivalentes , Membranas Artificiales , Concentración de Iones de Hidrógeno
5.
Fish Shellfish Immunol ; 136: 108737, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37030560

RESUMEN

Aeromonas hydrophila (A. hydrophila), a gram-negative bacterium, causes serious diseases with various clinical symptoms in farm raised fish. Thus, different ways to prevent and control A. hydrophila infection need to be explored, including a vaccine. In this study, we evaluated the protective efficacy of an oral vaccine prepared from the A. hydrophila TPS maltoporin (Malt) with Lactobacillus plantarum (L. plantarum) against A. hydrophila infection in crucian carp (Carassius auratus). For the in vivo experiment, the oral vaccine was administered to crucian carp by feeding them fish diets containing Lp-pPG-Malt, Lp-pPG and PBS for 28 days. The enzyme-linked immunosorbent assay (ELISA), leukocyte phagocytosis assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to measure the protective efficacy of the Lp-pPG-Malt. ELISA and leukocyte phagocytosis assay confirmed that Lp-pPG-Malt significantly enhanced the IgM level and nonspecific immune response of crucian carp compared with the control groups (Lp-pPG and PBS). The RT-qPCR results showed that the Lp-pPG-Malt increased the relative expression of immune-related genes (IL-10, IL-1ß, TNF-α, IFN-γ) of crucian carp in various tissues (liver, spleen, head kidney and hind intestine). Moreover, Lp-pPG-Malt significantly increased the relative percent survival of fish after intraperitoneal injection with A. hydrophila (55%) compared with the Lp-pPG and PBS groups (0%). These findings suggest that Lp-pPG-Malt can serve as an oral vaccine candidate for A. hydrophila infection and that Malt can be used as an effective antigen in crucian carp farming.


Asunto(s)
Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Lactobacillus plantarum , Animales , Aeromonas hydrophila , Vacunas Bacterianas , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria
6.
Fish Shellfish Immunol ; 140: 108973, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37481101

RESUMEN

Vibrio mimicus (V. mimicus) is known to cause severe bacterial diseases with high mortality rates in fish, resulting in significant economic losses in the global aquaculture industry. Therefore, the objective of this study was to develop a safe and effective vaccine for protecting Carassius auratus (C. auratus) against V. mimicus infection. Recombinant Lactobacillus casei (L. casei) strains, Lc-pPG-612-OmpU and Lc-pPG-612-OmpU-CTB (surface-displayed), were constructed using a L. casei strain (ATCC 393) as an antigen delivery carrier and the cholera toxin B subunit (CTB) as an adjuvant. The two recombinant strains of L. casei were administered to C. auratus via oral immunization, and the protective efficacy of the oral vaccines was assessed. The results demonstrated that oral immunization with the two strains significantly increased the levels of nonspecific immune indicators in C. auratus, including alkaline phosphatase (AKP), lysozyme (LYS), acid phosphatase (ACP), complement 3 (C3), complement 4 (C4), lectin, and superoxide dismutase (SOD). Moreover, the experiment groups exhibited significant increases in specific immunoglobulin M (IgM) antibodies against OmpU, as well as the transcription of immune-related genes (ie., IL-1ß, TNF-α, IL-10, and TGF-ß), when compared to the control groups. Following infection of C. auratus with V. mimicus, the mortality rate of the recombinant L. casei-treated fish was observed to be lower compared to the control group. This finding suggests that recombinant L. casei demonstrates effective protection against V. mimicus infection in C. auratus. Furthermore, the addition of the immune adjuvant CTB was found to induce a more robust adaptive and innate immune response in C. auratus, resulting in reduced mortality after infection with V. mimicus.


Asunto(s)
Carpas , Lacticaseibacillus casei , Vibriosis , Vibrio mimicus , Animales , Carpa Dorada , Vacunas Bacterianas , Vibriosis/prevención & control , Vibriosis/veterinaria
7.
Fish Shellfish Immunol ; 135: 108659, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36868535

RESUMEN

Vibrio mimicus (V. mimicus) is a pathogenic bacterium that causes diseases in humans and various aquatic animals. A particularly efficient way to provide protection against V. mimicus is through vaccination. However, there are few commercial vaccines against V. mimics, especially oral vaccines. In our study, two surface-display recombinant Lactobacillus casei (L. casei) Lc-pPG-OmpK and Lc-pPG-OmpK-CTB were constructed using L. casei ATCC393 as an antigen delivery vector, outer membrane protein K (OmpK) of V. mimicus as an antigen, and cholera toxin B subunit (CTB) as a molecular adjuvant; furthermore, the immunological effects of recombinant L.casei in Carassius auratus (C. auratus) were assessed. The results indicated that oral recombinant L.casei Lc-pPG-OmpK and Lc-pPG-OmpK-CTB stimulated higher levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), lysozyme (LYS), lectin, C3, and C4 in C. auratus, compared with control groups (Lc-pPG group and PBS group). Furthermore, the expression of interleukin-1ß (IL-1ß), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and transforming growth factor-ß (TGF-ß) in the liver, spleen, head kidney, hind intestine and gills of C. auratus was significantly increased, compared with that in the controls. These results demonstrated that the two recombinant L. casei strains could effectively trigger humoral and cellular immunity in C. auratus. In addition, two recombinant L.casei strains were able to survive and colonize the intestine of C. auratus. Importantly, after being challenged with V. mimicus, C. auratus fed Lc-pPG-OmpK and Lc-pPG-OmpK-CTB exhibited greater survival rates than the controls (52.08% and 58.33%, respectively). The data showed that recombinant L. casei could elicit a protective immunological response in C. auratus. The effect of the Lc-pPG-OmpK-CTB group was better than that of the Lc-pPG-OmpK group, and Lc-pPG-OmpK-CTB was found to be an effective candidate for oral vaccination.


Asunto(s)
Lacticaseibacillus casei , Vibrio mimicus , Humanos , Animales , Lacticaseibacillus casei/genética , Carpa Dorada , Vacunación , Adyuvantes Inmunológicos , Proteínas Recombinantes
8.
Acta Pharmacol Sin ; 44(4): 822-831, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36216898

RESUMEN

The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.


Asunto(s)
Hipertermia Inducida , Leucemia Promielocítica Aguda , Humanos , Antineoplásicos/farmacología , Trióxido de Arsénico/uso terapéutico , Células HeLa , Leucemia Promielocítica Aguda/terapia , Leucemia Promielocítica Aguda/tratamiento farmacológico , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Proteínas de Fusión Oncogénica/uso terapéutico , Proteína de la Leucemia Promielocítica con Dedos de Zinc/genética , Tretinoina/farmacología , Tretinoina/uso terapéutico
9.
Proc Natl Acad Sci U S A ; 117(34): 20803-20813, 2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32764148

RESUMEN

Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric vesicular stomatitis virus (VSV) containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small-molecule inhibitors of the main endosomal phosphatidylinositol-3-phosphate/phosphatidylinositol 5-kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Ebolavirus/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Morfolinas/farmacología , Fosfatidilinositol 3-Quinasas , Triazinas/farmacología , Internalización del Virus/efectos de los fármacos , Animales , Betacoronavirus/fisiología , COVID-19 , Células Cultivadas , Infecciones por Coronavirus , Ebolavirus/fisiología , Edición Génica , Humanos , Hidrazonas , Pandemias , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Neumonía Viral , Pirimidinas , SARS-CoV-2 , Proteínas del Envoltorio Viral/genética
10.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36674444

RESUMEN

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by DHCR24). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland's inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of Dhcr24 in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of Dhcr24 in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.


Asunto(s)
Corticosterona , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Humanos , Ratones , Femenino , Ratas , Animales , Corticosterona/metabolismo , Glándulas Suprarrenales/metabolismo , Zona Fascicular/metabolismo , Colesterol/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/genética
11.
Microb Pathog ; 167: 105559, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35568093

RESUMEN

With the aim to discover novel lactic acid bacteria and Bacillus strains from fish as potential probiotics to replace antibiotics in aquaculture, the present study was conducted to isolate lactic acid bacteria and Bacillus from intestinal tract of healthy crucian carp (Carassiu auratus) and largemouth bass (Micropterus salmoides) and evaluate their resistance against Aeromonas veronii. Based on the evaluation of antibacterial activity and tolerance test, one strain of lactic acid bacteria (Weissella cibaria C-10) and one strain of Bacillus (Bacillus amyloliquefaciens T-5) with strong environmental stability were screened out. The safety evaluation showed that these two strains were non-toxic to crucian carp and were sensitive to most antibiotics. In vivo study, the crucian carps were fed a basal diet supplemented with W. cibaria C-10 (C-10), B. amyloliquefaciens T-5 (T-5) and W. cibaria C-10 + B. amyloliquefaciens T-5 (C-10+T-5), respectively, for 5 weeks. Then, various immune parameters were measured at 35 days of post-feeding. Results showed both probiotics could improve the activities of related immune enzymes, immune factors and non-specific immune antibodies in blood and organs (gill, gut, kidney, liver, and spleen) of crucian carp in varying degrees. Moreover, after 7 days of challenge experiment, the survival rates after challenged with A. veronii of W. cibaria C-10 (C-10), B. amyloliquefaciens T-5 (T-5) and W. cibaria C-10 + B. amyloliquefaciens T-5 (C-10+T-5) supplemented groups to the crucian carps were 20%, 33% and 22%, respectively. Overall, W. cibaria C-10 and B. amyloliquefaciens T-5 could be considered to be developed into microecological preparations for the alternatives of antibiotics in aquaculture.


Asunto(s)
Bacillus amyloliquefaciens , Bacillus , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Probióticos , Aeromonas veronii , Animales , Antibacterianos/farmacología , Suplementos Dietéticos , Enfermedades de los Peces/microbiología , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Weissella
12.
Microb Pathog ; 167: 105566, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35568092

RESUMEN

Aeromonas veronii (A. veronii) is a pathogen that can infect aquatic organisms and mammals and has caused irrecoverable economic losses to the aquaculture industry. The results of an epidemiological investigation showed that the number of cases of A. veronii have increased gradually in recent years, and its drug resistance and virulence has shown an upward trend. In this study, we constructed an A. veronii mutant strain Δlip, by homologous recombination and studied its function. The results showed that there was no significant difference in the biofilm formation ability between the Δlip and the wild-type strain, but the toxicity of the Δlip to EPC cells and its ability to adhere to EPC cells were significantly reduced. The LD50 value of the Δlip to zebrafish was 7.40-fold higher than that of the wild-type strain. In addition, after 24 h and 72 h, the bacterial loads of the Δlip in the organs of crucian carp were significantly lower than those in the wild-type strain. In conclusion, the mutant strain Δlip led to a decrease in the adhesion and virulence of the wild-type strain, which lays a foundation to further understand lip gene function and the pathogenic mechanism of A. veronii.


Asunto(s)
Aeromonas , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Aeromonas/genética , Aeromonas veronii/genética , Animales , Enfermedades de los Peces/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Labio , Mamíferos , Virulencia/genética , Pez Cebra/microbiología
13.
PLoS Genet ; 15(6): e1008226, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31199789

RESUMEN

Carbonic anhydrase-8 (CA8) is an intracellular protein that functions as an allosteric inhibitor of inositol trisphosphate receptor-1 (ITPR1) critical to intracellular Ca++ release, synaptic functions and neuronal excitability. We showed previously that murine nociception and analgesic responses are regulated by the expression of this gene in dorsal root ganglion (DRG) associated with a cis-eQTL. In this report, we identify an exon-level cis-eQTL (rs6471859) that regulates human DRG CA8 alternative splicing, producing a truncated 1,697bp transcript (e.g., CA8-204). Our functional genomic studies show the "G" allele at rs6471859 produces a cryptic 3'UTR splice site regulating expression of CA8-204. We developed constructs to study the expression and function of the naturally occurring CA8-204G transcript (G allele at rs6471859), CA8-204C (C allele at rs6471859 reversion mutation) and CA8-201 (full length transcript). CA8-204G transcript expression occurred predominantly in non-neuronal cells (HEK293), while CA8-204C expression was restricted to neuronal derived cells (NBL) in vitro. CA8-204G produced a stable truncated transcript in HEK293 cells that was barely detectable in NBL cells. We also show CA8-204 produces a stable peptide that inhibits pITPR1 and Ca++ release in HEK293 cells. These results imply homozygous G/G individuals at rs6471859, which are common in the general population, produce exclusively CA8-204G that is barely detectable in neuronal cells. CA8 null mutations that greatly impact neuronal functions are associated with severe forms of spinal cerebellar ataxia, and our data suggest G/G homozygotes should display a similar phenotype. To address this question, we show in vivo using AAV8-FLAG-CA8-204G and AAV8-V5-CA8-201 gene transfer delivered via intra-neural sciatic nerve injection (SN), that these viral constructs are able to transduce DRG cells and produce similar analgesic and anti-hyperalgesic responses to inflammatory pain. Immunohistochemistry (IHC) examinations of DRG tissues further show CA8-204G peptide is expressed in advillin expressing neuronal cells, but to a lesser extent compared to glial cells. These findings explain why G/G homozygotes that exclusively produce this truncated functional peptide in DRG evade a severe phenotype. These genomic studies significantly advance the literature regarding structure-function studies on CA8-ITPR1 critical to calcium signaling pathways, synaptic functioning, neuronal excitability and analgesic responses.


Asunto(s)
Biomarcadores de Tumor/genética , Señalización del Calcio/genética , Receptores de Inositol 1,4,5-Trifosfato/genética , Neuronas/metabolismo , Dolor/genética , Empalme Alternativo/genética , Animales , Biomarcadores de Tumor/farmacología , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Técnicas de Transferencia de Gen , Células HEK293 , Humanos , Ratones , Mutación/genética , Neuronas/patología , Especificidad de Órganos , Dolor/patología , Péptidos/genética , Péptidos/farmacología , Sitios de Carácter Cuantitativo/genética , Sitios de Empalme de ARN/genética , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo
14.
Int J Mol Sci ; 24(1)2022 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-36613764

RESUMEN

As a worldwide health issue, obesity is associated with the infiltration of monocytes/macrophages into the adipose tissue causing unresolved inflammation. Monocyte chemoattractant protein-1 (MCP-1) exerts a crucial effect on obesity-related monocytes/macrophages infiltration. Clinically, aspirin and salsalate are beneficial for the treatment of metabolic diseases in which adipose tissue inflammation plays an essential role. Herein, we investigated the effect and precise mechanism of their active metabolite salicylate on TNF-α-elevated MCP-1 in adipocytes. The results indicated that salicylate sodium (SAS) could lower the level of MCP-1 in TNF-α-stimulated adipocytes, which resulted from a previously unrecognized target phosphodiesterase (PDE), 3B (PDE3B), rather than its known targets IKKß and AMPK. The SAS directly bound to the PDE3B to inactivate it, thus elevating the intracellular cAMP level and activating PKA. Subsequently, the expression of MKP-1 was increased, which led to the decrease in p-EKR and p-p38. Both PDE3B silencing and the pharmacological inhibition of cAMP/PKA compromised the suppressive effect of SAS on MCP-1. In addition to PDE3B, the PDE3A and PDE4B activity was also inhibited by SAS. Our findings identify a previously unrecognized pathway through which SAS is capable of attenuating the inflammation of adipocytes.


Asunto(s)
Quimiocina CCL2 , Factor de Necrosis Tumoral alfa , Humanos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/metabolismo , Quimiocina CCL2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adipocitos/metabolismo , Inflamación/metabolismo , Obesidad/metabolismo , Salicilatos/farmacología
15.
Water Sci Technol ; 85(10): 2928-2944, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35638797

RESUMEN

The persistence of antibiotics in sewage treatment plants in recent years has become a serious problem. Meanwhile, humic acid and ammonia nitrogen are widely distributed in natural reservoirs and might influence the sorption, migration and transformation of antibiotics. In this study, natural zeolite (NZ) was evaluated as an adsorbent for the removal of levofloxacin (LEV). The physical and chemical properties of NZ before and after adsorption were characterized by various analytical techniques to develop the mechanism. The effects of ammonia nitrogen and humic acid (HA) on the interfacial behavior of LEV on NZ were explored. Comparative experiments revealed that LEV adsorption on NZ involved electrostatic interactions and ion exchange, and the adsorption processes were well fitted by the Langmuir isotherm model and pseudosecond-order kinetic model. The maximum experimental adsorption capacity of LEV was 22.17 mg·g-1 at pH 6.5. The presence of ammonia nitrogen and HA significantly suppressed the adsorption of LEV due to competitive adsorption, and the adsorption capacity decreased 58 and 46%, respectively. It is obvious that low concentrations of ammonia nitrogen and HA are conducive to improving the treatment effect of sewage. This study demonstrates that NZ is a promising and efficient material for LEV adsorption.


Asunto(s)
Sustancias Húmicas , Zeolitas , Adsorción , Amoníaco , Antibacterianos , Levofloxacino/química , Nitrógeno , Aguas del Alcantarillado , Zeolitas/química
16.
Environ Monit Assess ; 195(1): 192, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36512138

RESUMEN

Wetlands are fragile ecosystems that are sensitive to human activities. In mining cities with high groundwater tables, underground mining, urbanization, and land reclamation cause severe disturbance to wetland landscape patterns, which poses a serious threat to the integrity and sustainability of the regional wetland ecosystems. This paper extracted the dynamic patterns of wetlands in Huaibei, China, from the Landsat TM/ETM remote sensing images with a time duration of 30 years from 1991 to 2021. The land-use transfer matrix and the landscape metrics were used to analyze the dynamic evolution of the wetland landscape patterns in this typical mining city. Afterwards, the human disturbance changes in the wetlands during the past 30 years were analyzed by the human disturbance transformation index (HTI). The correlation between the HTI and the changes in the landscape metrics were analyzed to reflect the influences of different human disturbance mechanisms on the evolution of the wetland landscape patterns. The results indicated that the wetland areas gradually increased with rising human disturbance levels from 1991 to 2021. However, the wetland landscape patterns showed a trend of declining landscape connectivity and fragmentation. The human disturbance levels to the wetlands were found significantly increased from 1991 to 2005 and from 2010 to 2015, and declined from 2005 to 2010 and from 2015 to 2021. The correlation between the HTI and landscape metrics indicates that current ecological restoration planning has limitations in improving the wetland landscape patterns. In the future, it is necessary to formulate systematic wetland landscape patterns restoration planning that covers the overall area according to the evolutionary trend of wetlands.


Asunto(s)
Ecosistema , Humedales , Humanos , Ciudades , Conservación de los Recursos Naturales/métodos , Monitoreo del Ambiente/métodos , China
17.
Fa Yi Xue Za Zhi ; 38(6): 754-762, 2022 Dec 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-36914392

RESUMEN

Exosomes are membranous tiny vesicles secreted by cells, which are widely found in the extracellular matrix and various body fluids and carry a variety of biologically functional molecules such as proteins, lipids, messenger RNA (mRNA) and microRNA (miRNA). Exosomes not only play important biological roles in the field of immunology and oncology, but also have potential application value in the field of forensic medicine. This article reviews the discovery, production and degeneration mechanism, biological functions, isolation and identification methods of exosomes, summarizes the research on exosomes and their significance in the field of forensic science, and discusses their applications in body fluid identification, individual identification, postmortem interval estimation to provide ideas for the application of exosomes in forensic work.


Asunto(s)
Exosomas , MicroARNs , Exosomas/genética , Exosomas/metabolismo , Medicina Legal , MicroARNs/genética , MicroARNs/metabolismo , Ciencias Forenses , ARN Mensajero/genética , ARN Mensajero/metabolismo
18.
Angew Chem Int Ed Engl ; 61(3): e202115443, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-34799948

RESUMEN

Metal-organic frameworks (MOFs) membranes with high pore density and tunable pore size down to the subnanoscale exhibit great potential in ion separation when appropriately designed and prepared. By a washing-assisted secondary growing method, a well intergrown UiO-67 membrane with preferential growth along the [022] direction was synthesized on a polyvinylpyrrolidone (PVP)-modified AAO substrate. Because of the oriented growth of UiO-67 nanocrystals, highly interconnected ion-transporting channels are created throughout the UiO-67/AAO membrane capable of achieving an ultrahigh Li+ permeance of 27.01 mol m-2 h-1 as well as very decent Li+ /Mg2+ selectivity of up to 159.4. Molecular dynamics simulations reveal that the high selectivity is associated with the large disparity of the transport energy barrier between Li+ and Mg2+ , which is caused by different extents of ion dehydration in unique bimodal and oriented membrane channels.

19.
Microb Pathog ; 159: 105134, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34400283

RESUMEN

Aeromonas veronii (A. veronii, AV) strains are emerging zoonotic and aquatic pathogens, yet we know very little about their genomics. This study aims to utilize comparative genomics to investigate the intraspecific genetic diversity, differences in virulence factors and evolutionary mechanisms of A. veronii strains from diverse sources and to fundamentally demonstrate their pathogenic mechanisms. We conducted comparative genomics analysis of 39 A. veronii strains from different sources and found that 1993 core genes are shared by these strains and that these shared core genes may be necessary to maintain the basic characteristics of A. veronii. Additionally, phylogenetic relationship analysis based on these shared genes revealed that a distant relationship between the AMC34 strain and the other 38 strains but that, the genetic relationship among the 38 strains is relatively close, indicating that AMC34 may not belong to A. veronii. Furthermore, analysis of shared core genes and average nucleotide identity (ANI) values showed no obvious correlation with the location of A. veronii isolation and genetic relationship. Our research indicates the evolutionary mechanism of A. veronii from different sources and provides new insights for a deeper understanding of its pathogenic mechanism.


Asunto(s)
Aeromonas , Infecciones por Bacterias Gramnegativas , Aeromonas/genética , Aeromonas veronii/genética , Genómica , Humanos , Filogenia , Factores de Virulencia/genética
20.
Microb Pathog ; 155: 104898, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33878398

RESUMEN

Salmonellosis is a worldwide zoonotic disease that poses a serious threat to the reproduction of livestock and poultry and the health of young animals. Probiotics including Bacillus species, have received increasing attention as a substitute for antibiotics. In this study, chicks infected with Salmonella were fed feed supplemented with the BSH to observe the pathological changes in the liver, detect the number of viable bacteria in the liver and spleen, and record the death of the chicks. The results showed that BSH could reduce the pathological changes in the liver and the invasion of Salmonella into the liver and spleen of chicks. In addition, the survival rate of chicks in the BSH experimental group was 60%, while that in the infected control group was 26%, indicating that BSH had a protective effect on chicks infected with Salmonella. Finally, the fecal microflora of 9-day-old chicks was analyzed by 16S rRNA high-throughput sequencing. The results showed that Salmonella infection could cause intestinal flora changes, while BSH could alleviate this change. In addition, BSH also promoted the proliferation of Lactobacillus salivarius in the cecum of chick. This study emphasized that BSH has anti- Salmonella infection effects in chickens and can be used as a candidate microecological preparation strain.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades de las Aves de Corral , Probióticos , Salmonelosis Animal , Alimentación Animal , Animales , Bacillus subtilis , Ciego , Pollos , Enfermedades de las Aves de Corral/prevención & control , ARN Ribosómico 16S/genética , Salmonelosis Animal/prevención & control
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