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1.
Mol Breed ; 44(3): 17, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38371313

RESUMO

Heading date is one of the important agronomic traits that affects rice yield. In this study, we cloned a new rice B3 family gene, OsL1, which regulates rice heading date. Importantly, osl1-1 and osl1-2, two different types of mutants of OsL1 were created using the gene editing technology CRISPR/Cas9 system and exhibited 4 days earlier heading date than that of the wild type under short-day conditions. Subsequently, the plants overexpressing OsL1, OE-OsL1, showed a 2-day later heading date than the wild type in Changsha and a 5-day later heading date in Lingshui, but there was no significant difference in other yield traits. Moreover, the results of subcellular localization study indicated that OsL1 protein was located in the nucleus and the expression pattern analysis showed that OsL1 gene was expressed in rice roots, stems, leaves, and panicles, and the expression level was higher at the root and weak green panicle. In addition, the OsL1 gene was mainly expressed at night time under short-light conditions. The transcriptomic analysis indicated that OsL1 might be involved in the Hd1-Hd3a pathway function. Together, our results revealed that the cloning and functional analysis of OsL1 can provide new strategy for molecular design breeding of rice with suitable fertility period. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01444-1.

2.
J Neuroinflammation ; 20(1): 294, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071333

RESUMO

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.


Assuntos
Medula Óssea , Osteopontina , Acidente Vascular Cerebral , Animais , Camundongos , Isquemia , Osteopontina/metabolismo , Crânio/metabolismo
3.
J Neuroinflammation ; 20(1): 270, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978532

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. METHODS: A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. RESULTS: The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH. CONCLUSIONS: Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.


Assuntos
Lesões Encefálicas , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Camundongos , Masculino , Animais , Monócitos , Hemorragia Subaracnóidea/complicações , Lesões Encefálicas/etiologia , Macrófagos , Camundongos Endogâmicos C57BL
4.
Chemistry ; 29(23): e202203818, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-36638350

RESUMO

A highly efficient NHC-catalyzed cycloaddition of (E)-alkenylisatins and γ-chloroenals with a broad substrate scope has been developed to provide spiro[cyclohex-4-ene-1,3'-indole] in good yields (up to 99 % yield) with excellent diastereo- and enantioselectivities (up to >20 : 1 d.r., >99 % ee) under mild conditions without the use of metal and additives. Based on computational investigations, the role of the NHC on the diastereo- and enantioselectivity is discussed.

5.
Chem Rec ; 23(7): e202200279, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36916715

RESUMO

Over the recent decades, due to the special electronic characteristics and diverse reactivities, N-heterocyclic carbene (NHC) has received significant interest in organocatalyzed reactions. The formation of Breslow intermediates by NHC can convert into acyl anion equivalent, enolates, homoenolate, acyl azolium, and vinyl enolate etc., and the cycloaddition reactions of these species has attracted lots of attention. In this review, we focus on the summry of the development of NHC-activation of carbonyl carbon (or imine carbon) in situ, α-, ß-, γ-, and beyond, and the cycloaddition reaction of these species.


Assuntos
Carbono , Ácidos Carboxílicos , Reação de Cicloadição , Iminas
6.
J Craniofac Surg ; 34(8): e739-e743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37418618

RESUMO

Glossopharyngeal neuralgia (GPN) is an uncommon facial pain syndrome and is characterized by paroxysms of excruciating pain in the distributions of the auricular and pharyngeal branches of cranial nerves IX and X. Glossopharyngeal neuralgia characterized by otalgia alone is rare. Herein, the authors analyzed 2 patients with GPN with otalgia as the main clinical manifestation. The clinical features and prognosis of this rare group of patients with GPN were discussed. They both presented with paroxysmal pain in the external auditory meatus and preoperative magnetic resonance imaging suggested the vertebral artery were closely related to the glossopharyngeal nerves. In both patients, compression of the glossopharyngeal nerve was confirmed during microvascular decompression, and the symptoms were relieved immediately after surgery. At 11 to 15 months follow-up, there was no recurrence of pain. A variety of reasons can cause otalgia. The possibility of GPN is a clinical concern in patients with otalgia as the main complaint. The authors think the involvement of the glossopharyngeal nerve fibers in the tympanic plexus via Jacobson nerve may provide an important anatomic basis for GPN with predominant otalgia. Surface anesthesia test of the pharynx and preoperative magnetic resonance imaging is helpful for diagnosis. Microvascular decompression is effective in the treatment of GPN with predominant otalgia.


Assuntos
Doenças do Nervo Glossofaríngeo , Cirurgia de Descompressão Microvascular , Humanos , Estudos Retrospectivos , Dor de Orelha/diagnóstico , Dor de Orelha/etiologia , Doenças do Nervo Glossofaríngeo/diagnóstico por imagem , Doenças do Nervo Glossofaríngeo/cirurgia , Nervo Glossofaríngeo/cirurgia , Dor/etiologia , Cirurgia de Descompressão Microvascular/efeitos adversos
7.
Int J Mol Sci ; 24(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37958699

RESUMO

Obesity, a major global health issue, is increasingly associated with the integral role of long non-coding RNA (lncRNA) in adipogenesis. Recently, we found that lncRNA-MSTRG4710 was highly expressed in the liver of rabbits fed a high-fat diet, but whether it is involved in lipid metabolism remains unclear. A series of experiments involving CCK-8, EDU, qPCR, and Oil Red O staining demonstrated that the overexpression of MSTRG4710 stimulated the proliferation and differentiation of preadipocytes while its knockdown inhibited these processes. Bioinformatics analysis showed that miR-29b-3p was a potential target gene of MSTRG4710, and IGF1 was a downstream target gene of miR-29b-3p. Luciferase reporter gene analysis and qPCR analysis confirmed that miR-29b-3p was a potential target gene of MSTRG4710, and miR-29b-3p directly targeted the 3'UTR of IGF1. The overexpression of miR-29b-3p was observed to regulate IGF1 protein and mRNA levels negatively. Additionally, a total of 414 known differentially expressed genes between the miR-29b-3p mimic, miR-29b-3p negative control (NC), siMSTRG4710, and siMSTRG4710-NC group were screened via transcriptome sequencing technology. The GO- and KEGG-enriched pathways were found to be related to lipid metabolism. The study also established that miR-29b-3p targets IGF1 to inhibit preadipocyte proliferation and differentiation. Notably, IGF1 knockdown significantly reduced preadipocyte proliferation and differentiation. Furthermore, co-transfection of pcDNA3.1(+)-MSTRG4710 and mimics into rabbit preadipocytes revealed that the mimics reversed the promotional effect of pcDNA3.1(+)-MSTRG4710. In conclusion, these results uncover that MSTRG4710 positively regulated cell proliferation and adipogenesis by the miR-29b-3p/IGF1 axis. Our findings might provide a new target for studying adipogenesis in rabbit preadipocytes and obesity.


Assuntos
MicroRNAs , RNA Longo não Codificante , Animais , Coelhos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Obesidade
8.
Int J Mol Sci ; 24(18)2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37762324

RESUMO

Obesity has become a major health problem worldwide, and increasing evidence supports the importance of microRNAs (miRNAs) in its pathogenesis. Recently, we found that miR-383-5p_1 is highly expressed in the perirenal fat of high-fat-fed rabbits, but it is not yet known whether miR-383-5p is involved in lipid metabolism. Here, we used transcriptome sequencing technology to screen 1642 known differentially expressed genes between miR-383-5p mimic groups and miR-383-5p negative control groups. Gene Ontology Resource (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched in the pathway related to lipid metabolism, and glycine biosynthesis, the NOD receptor signal pathway and nonalcoholic fatty liver were significantly enriched. Afterwards, our research results indicated that miR-383-5p can promote the proliferation and differentiation of rabbit preadipocytes, and there is a direct targeting relationship with RAD51AP1. Mechanistically, miR-383-5p directly interacts with the lipid metabolism and participates in adipogenesis and lipid accumulation by targeting RAD51AP1. In conclusion, our data highlight a physiological role for miRNA in lipid metabolism and suggest the miR-383-5p/RAD51AP1 axis may represent a potential mechanism for controlling lipid accumulation in obesity.


Assuntos
Lagomorpha , MicroRNAs , Animais , Coelhos , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , Obesidade , Proliferação de Células/genética , Lipídeos
9.
Curr Issues Mol Biol ; 43(3): 1558-1575, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34698087

RESUMO

DNA methylation and the alternative splicing of precursor messenger RNAs (pre-mRNAs) are two important genetic modification mechanisms. However, both are currently uncharacterized in the muscle metabolism of rabbits. Thus, we constructed the Tianfu black rabbit obesity model (obese rabbits fed with a 10% high-fat diet and control rabbits from 35 days to 70 days) and collected the skeletal muscle samples from the two groups for Genome methylation sequencing and RNA sequencing. DNA methylation data showed that the promoter regions of 599 genes and gene body region of 2522 genes had significantly differential methylation rates between the two groups, of which 288 genes had differential methylation rates in promoter and gene body regions. Analysis of alternative splicing showed 555 genes involved in exon skipping (ES) patterns, and 15 genes existed in differential methylation regions. Network analysis showed that 20 hub genes were associated with ubiquitinated protein degradation, muscle development pathways, and skeletal muscle energy metabolism. Our findings suggest that the two types of genetic modification have potential regulatory effects on skeletal muscle development and provide a basis for further mechanistic studies in the rabbit.


Assuntos
Processamento Alternativo , Metilação de DNA , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Músculo Esquelético/metabolismo , Obesidade/genética , Transcriptoma , Animais , Biomarcadores , Biologia Computacional/métodos , Ilhas de CpG , Dieta Hiperlipídica , Suscetibilidade a Doenças , Metabolismo Energético , Epigênese Genética , Éxons , Sequenciamento de Nucleotídeos em Larga Escala , Obesidade/metabolismo , Coelhos
10.
Chemistry ; 26(54): 12349-12354, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32596851

RESUMO

An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple NiII salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.

11.
Biochem Biophys Res Commun ; 507(1-4): 324-329, 2018 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-30448057

RESUMO

MYB transcription factors play important roles in the regulation of phenylpropanoid biosynthesis. However, the knowledge regarding the roles of CCA1-like MYBs in phenylpropanoid pathway is limited in plants. Previously, we identified 54 CCA1-like proteins in soybean. In the study, a CCA1-like MYB (GmMYB133) was functionally characterized as a positive regulator in isoflavonoid synthesis. GmMYB133 encodes a 330 aa protein featured with one CCA1 conserved motif. Further analysis indicated that the expression pattern of GmMYB133 was near-perfectly correlated with isoflavonoid accumulation as soybean embryos develop. GmMYB133 over-expression promoted the expression of two key isoflavonoid biosynthetic genes (GmCHS8 and GmIFS2) and increased total isoflavonoid content in hairy roots. Protein-protein interaction assays indicated that GmMYB133 might form hetero- and homodimers with an isoflavonoid regulator GmMYB176 and itself, respectively, while the subcellular localization of GmMYB133 can be altered by its interaction with 14-3-3 protein. These findings provided new insights into the functional roles of CCA1-like MYB proteins in the regulation of phenylpropanoid pathway, and will contribute to the future genetic engineering in the improvement of soybean seed quality.


Assuntos
Vias Biossintéticas , Glycine max/metabolismo , Isoflavonas/biossíntese , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Mapas de Interação de Proteínas , Glycine max/embriologia , Glycine max/genética
12.
Waste Manag ; 186: 166-175, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38905906

RESUMO

Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in livestock feces, and their removal is crucial for sustainable soil-ecosystem development. Physical and chemical approaches to extract tetracycline may have adverse effects on soil ecosystems, but no studies have thus far examined the potential for biological methods, such as collective degradation action of soil fauna. Thus, this study aimed to investigate the synergistic effects of lactic acid bacteria (LAB) and earthworms (Eisenia fetida) on biodegradation of tetracycline residues in sheep manure. We assessed earthworm biomass, tetracycline residue, and bacterial communities in both earthworm intestines and vermicompost. Earthworm biomass and tetracycline degradation efficiency increased significantly with LAB addition, with a degradation rate of up to 80.16%. This increase may be attributable to LAB acting as electron donors to spur tetracycline degradation. Additionally, we noted that tetracycline presence significantly influenced bacterial communities in earthworm intestines and vermicompost, elevating the abundance of potential pathogenic bacteria (e.g., Flavobacterium, Gammaproteobacteria, and Enterobacteriaceae). This finding suggests that heightened environmental stress from antibiotics could actually facilitate the growth of less prevalent bacteria, including potential pathogens. In conclusion, our study provides evidence supporting the effectiveness of LAB and earthworms in degrading tetracycline residues. In particular, LAB appears to mitigate stress from tetracycline exposure in earthworms, thus increasing their vermicomposting efficacy. Our work has important implications for soil management, with the potential to enhance pollution clean-up rates while minimizing negative side-effects to soil microbial communities.

13.
Animals (Basel) ; 14(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38929360

RESUMO

This study used feces from 0-day-old (36 rabbits), 10-day-old (119 rabbits), and 60-day-old (119 rabbits) offspring rabbits and their corresponding female rabbits (36 rabbits) as experimental materials. Using 16s rRNA sequencing, the study analyzed the types and changes of gut microbiota in rabbits at different growth and development stages, as well as the correlation between gut microbiota composition and the weight of 60-day-old rabbits. All experimental rabbits were placed in the same rabbit shed. Juvenile rabbits were fed solid feed at 18 days of age and weaned at 35 days of age. In addition to identifying the dominant bacterial phyla of gut microbiota in rabbits at different age stages, it was found that the abundance of Clostridium tertium and Clostridium paraputrificum in all suckling rabbits (10-day-old) was significantly higher than that in rabbits fed with whole feed (60-day-old) (p < 0.05), while the abundance of Gram-negative bacterium cTPY13 was significantly lower (p < 0.05). In addition, Fast Expected Maximum Microbial Source Tracing (FEAST) analysis showed that the contribution of female rabbits' gut microbiota to the colonization of offspring rabbits' gut microbiota was significantly higher than that of unrelated rabbits' gut microbiota (p < 0.05). The contribution of female rabbits' gut microbiota to the colonization of gut microbiota in 0-day-old rabbits was significantly higher than that to the colonization of gut microbiota in the 10- and 60-day-old rabbits (p < 0.05). Finally, the correlation between gut microbiota composition and body weight of 60-day-old rabbits was analyzed based on a mixed linear model, and six ASVs significantly affecting body weight were screened. The above results provide important theoretical and practical guidance for maintaining gut health, improving growth and development performance, and feeding formulation in rabbits.

14.
Genes (Basel) ; 15(2)2024 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-38397164

RESUMO

In recent years, rising temperatures have caused heat stress (HS), which has had a significant impact on livestock production and growth, presenting considerable challenges to the agricultural industry. Research has shown that miR-425-5p regulates cellular proliferation in organisms. However, the specific role of miR-425-5p in bovine mammary epithelial cells (BMECs) remains to be determined. The aim of this study was to investigate the potential of miR-425-5p in alleviating the HS-induced proliferation stagnation in BMECs. The results showed that the expression of miR-425-5p significantly decreased when BMEC were exposed to HS. However, the overexpression of miR-425-5p effectively alleviated the inhibitory effect of HS on BMEC proliferation. Furthermore, RNA sequencing analysis revealed 753 differentially expressed genes (DEGs), comprising 361 upregulated and 392 downregulated genes. Some of these genes were associated with proliferation and thermogenesis through enrichment analyses. Further experimentation revealed that TOB2, which acts as a target gene of miR-425-5p, is involved in the regulatory mechanism of BMEC proliferation. In summary, this study suggests that miR-425-5p can promote the proliferation of BMECs by regulating TOB2. The miR-425-5p/TOB2 axis may represent a potential pathway through which miR-425-5p ameliorates the proliferation stagnation of BMECs induced by HS.


Assuntos
Glândulas Mamárias Animais , MicroRNAs , Animais , Bovinos , Proliferação de Células/genética , Células Epiteliais/metabolismo , Expressão Gênica , MicroRNAs/metabolismo , Glândulas Mamárias Animais/citologia , Feminino
15.
Mol Plant ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38956872

RESUMO

The discovery of a wild abortive-type cytoplasmic male sterile line and the breeding of its restorer line have led to the commercialization of three-line hybrid rice, which has contributed greatly to global food security. However, the molecular mechanisms underlying fertility abortion and the restoration of wild abortive-type cytoplasmic male sterile lines largely remain elusive. In this study, we cloned a restorer gene, Rf20, following a genome-wide association study analysis of the core parent lines of three-line hybrid rice. We found that Rf20 was present in all core parental lines, but different haplotypes and structural variants of its gene resulted in differences in Rf20 expression levels between sterile and restored lines. Rf20 could restore fertility in the wild abortive-type cytoplasmic male sterile line and was found to be responsible for fertility restoration in some cytoplasmic male sterile lines under high temperature. In addition, we found that Rf20 encodes a pentatricopeptide repeat protein that competes with WA352 for binding with COX11. This interaction enhances COX11's function as a scavenger of reactive oxygen species, which in turn restores pollen fertility. In this study, a new model of pentatricopeptide repeat proteins involved in the fertility recovery of cytoplasmic male sterile lines was proposed, which provides an important theoretical basis for the breeding of strong restorer lines and for overcoming high-temperature fertility recovery of some three-line sterile lines.

16.
J Alzheimers Dis ; 96(2): 623-631, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840492

RESUMO

BACKGROUND: No study has compared the risk of Alzheimer's disease (AD) in patients with brain tumors, gliomas, or glioblastomas with the risk in patients with other tumors. OBJECTIVE: To determine whether, compared with other tumors, brain tumors, gliomas, and glioblastomas increase the risk of AD. METHODS: This study identified a case group of 24,441 patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with only one primary tumor at age > 20 years in 1975-2019 and died from AD at age > 65 years as case group. The control group comprised 122,205 subjects from the SEER database who died from causes other than AD but otherwise had the same conditions as those in the case group. RESULTS: There was a significantly lower prevalence of glioma (0.074% versus 0.14%, p = 0.007) and glioblastoma (0.0082% versus 0.074%, p = 0.001) in patients who died from AD than in those who died from other causes, while brain tumors were not significantly associated with AD death (p = 0.227). When adjusted for factors including age at death, sex, race, tumor behavior, radiation therapy and tumor-directed surgery, glioblastoma was related to a significantly lower AD risk than other tumors (odds ratio: 0.19, 95% CI: 0.05-0.77). Additionally, patients who were older, female, American Indian/Alaska Native, had a benign tumor, radiation therapy and tumor-directed surgery had a significantly higher risk of dying from AD. CONCLUSION: Gliomas and glioblastomas were associated with a significantly lower risk of death from AD than other tumors.


Assuntos
Doença de Alzheimer , Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Feminino , Idoso , Glioblastoma/epidemiologia , Glioblastoma/patologia , Doença de Alzheimer/epidemiologia , Glioma/patologia , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia
17.
Eur J Pharmacol ; 956: 175956, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37541374

RESUMO

MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.


Assuntos
Lesões Encefálicas Traumáticas , Doenças do Sistema Nervoso Central , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , MicroRNAs/metabolismo , Neoplasias/tratamento farmacológico , Interferência de RNA , Resultado do Tratamento , Lesões Encefálicas Traumáticas/tratamento farmacológico , Doenças do Sistema Nervoso Central/terapia , Doenças do Sistema Nervoso Central/tratamento farmacológico
18.
Animals (Basel) ; 13(18)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37760279

RESUMO

At present, there is still room for research on the relationship between the vaginal microbiome and the reproductive health of dairy cows. In this study, high-throughput 16S rRNA sequencing technology was used to explore the differences of bacterial communities of dairy cows of different births, gain a deeper understanding of cow reproductive physiology, and maintain cow health. With the increase in parity, the number of vaginal flora decreased from 3511 to 469, but the number of species increased significantly, and Chao1 increased from 1226.41 ± 345.40 to 1467.76 ± 269.76. There was a significant difference in the number of vaginal microbiome functions between uncounted cows and calving cows. There was no significant difference in microbial diversity in calves. The relative abundance variation of vaginal microbiota in high-parity cows is less than that in low-parity cows. The amino acid metabolism of calves increased, the endocrine function of high-parity cows was enhanced, and the function of the vaginal microbiome increased after the first delivery, which gradually decreased with the increase in parity. This study also found that Methanobacteria and Caviibacter may be involved in amino acid metabolism and endocrine function, and they may play a key role in cow reproduction. This study provides an important theoretical basis for studying changes in vaginal microorganisms in dairy cows, improves the understanding of reproductive health and production performance, and provides a scientific basis for improving the reproductive management of dairy cows.

19.
Medicine (Baltimore) ; 102(44): e34780, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37933077

RESUMO

RATIONALE: Autoimmunity targeting glutamic acid decarboxylase 65 (GAD65) is associated with type 1 diabetes mellitus as well as various neurological diseases. In the central nervous system, GAD65 autoimmunity usually presents with limbic encephalitis, whereas extralimbic encephalitis (ELE) has only been reported in a few cases. Moreover, anti-GAD65 ELE in the paraneoplastic context has not yet been reported. PATIENT CONCERNS: A 60-year-old man presented with intermittent cough and sputum for 10 years, with no other diseases. The patient presented with recurrent seizures that were resistant to antiepileptic drugs (AEDs). Chest computed tomography and pathological results confirmed the diagnosis of small cell lung cancer. Paraneoplastic testing found a high level of GAD65 antibodies in his serum, and cerebrospinal fluid analysis revealed lymphocytic pleocytosis, indicating autoimmune encephalitis. Brain magnetic resonance imaging showed multifocal T2 fluid-attenuated inversion recovery hyperintensities in the extralimbic areas including the subcortex and deep white matter of the bilateral frontal lobe, parietal lobe, and insula lobes. DIAGNOSES: Finally, a diagnosis of anti-GAD65 autoimmune ELE with a paraneoplastic etiology from the small cell lung cancer was suspected. INTERVENTIONS: The patient refused any tumor-suppressive treatment or immunotherapy for potential side effects and only received AEDs levetiracetam, sodium valproate, and diazepam. OUTCOMES: The epilepsy of the patient was resistant to AEDs, and the patient died a week after discharge due to disease progression. LESSONS: Anti-GAD65 autoimmune encephalitis can be extralimbic, can present with isolated epilepsy, and extralimbic anti-GAD65 encephalitis can occur with an underlying malignancy.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Epilepsia , Encefalite Límbica , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Masculino , Humanos , Pessoa de Meia-Idade , Glutamato Descarboxilase , Epilepsia/terapia , Encefalite/diagnóstico , Encefalite Límbica/diagnóstico , Autoanticorpos
20.
Gene ; 883: 147656, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37479097

RESUMO

It was revealed in our previous study that the expression of miR-30c-5p in the skeletal muscle of rabbits fed high-fat diet was highly expressed. In the present study, we further investigated the function of miR-30c-5p in proliferation and differentiation of skeletal muscle satellite cell (SMSC). The results obtained in the present study showed that the skeletal muscle fibers of the rabbits fed the standard normal diet (SND) were orderly, regular, and uniform after HE staining, however, the muscle fibers of the rabbits fed the high-fat diet (HFD) were generally atrophied, some were arranged disorderly, the intercellular space was enlarged, the nucleus was increased, and the morphology and position were abnormal. Compared with the SND group, it was observed that the weekly weight gain and fat percentage were relatively higher, and also the levels of the serum biochemical indexes such as glucose, cholesterol, and triglyceride increased significantly in the rabbits fed with HFD. In addition, the results after the transfection of miR-30c-5p mimic, mimic NC (negative control), miR-30c-5p inhibitor, and inhibitor NC into the SMSCs showed that the cell counting kit-8 (CCK-8) proliferation experiment suggested that the number of cells in the over expression group was significantly lower than that in the mimic NC group at 48, 72, 96 h of cell proliferation. At 48, 72, 120 h, the number of cells in the inhibitor group was significantly higher than that in the mimic NC group. The number of EdU positive cells decreased significantly in the over expression group compared with the mimic NC group, however, it increased significantly in the inhibitor group compared with the inhibitor NC group. Moreover, compared with the mimic NC group, the myotube area increased significantly in the miR-30c-5p mimic group, whereas it decreased significantly in the miR-30c-5p inhibitor group as compared with the inhibitor NC group. In addition, we found that trinucleotide repeat containing adaptor 6A (TNRC6A) was successfully validated as a target gene for miR-30c-5p. The expression of TNRC6A in the miR-30c-5p mimic group was significantly lower than that in the mimic NC group. It was further observed that the expression of TNRC6A increased significantly in the miR-30c-5p inhibitor group as compared to that in the inhibitor NC group. Taken together, the results obtained in this study showed that miR-30c-5p promotes the differentiation as well as inhibits the proliferation of rabbit skeletal muscle satellite cells, and TNRC6A is a target gene of miR-30c-5p.


Assuntos
MicroRNAs , Células Satélites de Músculo Esquelético , Animais , Coelhos , Dieta Hiperlipídica/efeitos adversos , MicroRNAs/genética , MicroRNAs/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Obesidade/genética , Obesidade/metabolismo
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