Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 54
Filter
Add more filters

Country/Region as subject
Publication year range
1.
BMC Bioinformatics ; 24(1): 343, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715138

ABSTRACT

BACKGROUND: Genome-wide association studies (GWASes) aim to identify single nucleotide polymorphisms (SNPs) associated with a given phenotype. A common approach for the analysis of GWAS is single marker analysis (SMA) based on linear mixed models (LMMs). However, LMM-based SMA usually yields a large number of false discoveries and cannot be directly applied to non-Gaussian phenotypes such as count data. RESULTS: We present a novel Bayesian method to find SNPs associated with non-Gaussian phenotypes. To that end, we use generalized linear mixed models (GLMMs) and, thus, call our method Bayesian GLMMs for GWAS (BG2). To deal with the high dimensionality of GWAS analysis, we propose novel nonlocal priors specifically tailored for GLMMs. In addition, we develop related fast approximate Bayesian computations. BG2 uses a two-step procedure: first, BG2 screens for candidate SNPs; second, BG2 performs model selection that considers all screened candidate SNPs as possible regressors. A simulation study shows favorable performance of BG2 when compared to GLMM-based SMA. We illustrate the usefulness and flexibility of BG2 with three case studies on cocaine dependence (binary data), alcohol consumption (count data), and number of root-like structures in a model plant (count data).


Subject(s)
Genome-Wide Association Study , Bayes Theorem , Computer Simulation , Linear Models , Phenotype
2.
BMC Bioinformatics ; 24(1): 194, 2023 May 11.
Article in English | MEDLINE | ID: mdl-37170185

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) seek to identify single nucleotide polymorphisms (SNPs) that cause observed phenotypes. However, with highly correlated SNPs, correlated observations, and the number of SNPs being two orders of magnitude larger than the number of observations, GWAS procedures often suffer from high false positive rates. RESULTS: We propose BGWAS, a novel Bayesian variable selection method based on nonlocal priors for linear mixed models specifically tailored for genome-wide association studies. Our proposed method BGWAS uses a novel nonlocal prior for linear mixed models (LMMs). BGWAS has two steps: screening and model selection. The screening step scans through all the SNPs fitting one LMM for each SNP and then uses Bayesian false discovery control to select a set of candidate SNPs. After that, a model selection step searches through the space of LMMs that may have any number of SNPs from the candidate set. A simulation study shows that, when compared to popular GWAS procedures, BGWAS greatly reduces false positives while maintaining the same ability to detect true positive SNPs. We show the utility and flexibility of BGWAS with two case studies: a case study on salt stress in plants, and a case study on alcohol use disorder. CONCLUSIONS: BGWAS maintains and in some cases increases the recall of true SNPs while drastically lowering the number of false positives compared to popular SMA procedures.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Genome-Wide Association Study/methods , Bayes Theorem , Computer Simulation , Phenotype , Linear Models
3.
BMC Genomics ; 24(1): 621, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853328

ABSTRACT

BACKGROUND: Puberty marks the end of childhood and achieve sexual maturation and fertility. The role of hypothalamic proteins in regulating puberty onset is unclear. We performed a comprehensive differential proteomics and phosphoproteomics analysis in prepubertal and pubertal goats to determine the roles of hypothalamic proteins and phosphoproteins during the onset of puberty. RESULTS: We used peptide and posttranslational modifications peptide quantification and statistical analyses, and identified 69 differentially expressed proteins from 5,057 proteins and 576 differentially expressed phosphopeptides from 1574 phosphorylated proteins. Combined proteomic and phosphoproteomics, 759 correlated proteins were identified, of which 5 were differentially expressed only at the protein level, and 201 were only differentially expressed at the phosphoprotein level. Pathway enrichment analyses revealed that the majority of correlated proteins were associated with glycolysis/gluconeogenesis, Fc gamma R-mediated phagocytosis, focal adhesion, GABAergic synapse, and Rap1 signaling pathway. These pathways are related to cell proliferation, neurocyte migration, and promoting the release of gonadotropin-releasing hormone in the hypothalamus. CTNNB1 occupied important locations in the protein-protein interaction network and is involved in focal adhesion. CONCLUSION: The results demonstrate that the proteins differentially expression only at the protein level or only differentially expressed at the phosphoprotein level and their related signalling pathways are crucial in regulating puberty in goats. These differentially expressed proteins and phosphorylated proteins may constitute the proteomic backgrounds between the two different stages.


Subject(s)
Goats , Proteomics , Animals , Female , Humans , Goats/metabolism , Hypothalamus/metabolism , Puberty , Sexual Maturation/physiology , Gonadotropin-Releasing Hormone/metabolism , Phosphoproteins/metabolism
4.
J Am Chem Soc ; 145(51): 28204-28215, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38099712

ABSTRACT

With the increasing demand for functional polythiophenes in extensive applications such as organic solar cells, electronic skins, thermoelectric materials, and field effect transistors, efficient and economic synthetic approaches for polythiophenes are urgently required. In this work, KOH-assisted polymerizations of elemental sulfur and alkynones were developed to directly afford polythiophenes with various backbones, regioselective structures, and high molecular weights (Mns up to 20700 g/mol) in high yields (up to 97%) at 80 °C in 30 min. When the same polymerization was conducted at room temperature, stable and unique poly(1,4-dithiin)s (Mns up to 21800 g/mol) could be rapidly obtained in high yields (up to 87%) in 10 min. The temperature-controlled KOH-assisted polymerizations of sulfur and alkynones possessed high efficiency, mild conditions, and simple operation, which had provided an economic, efficient, and convenient approach for the direct conversion from elemental sulfur to functional polythiophenes and poly(1,4-dithiin)s with the in situ constructed aromatic or nonaromatic heterocycles embedded in the polymer backbones, demonstrating great synthetic simplicity, high efficiency, good selectivity, and robustness. It is anticipated to accelerate the development of semiconducting polymer materials and their applications.

5.
Biometrics ; 79(4): 3266-3278, 2023 12.
Article in English | MEDLINE | ID: mdl-37365985

ABSTRACT

We propose a Bayesian model selection approach for generalized linear mixed models (GLMMs). We consider covariance structures for the random effects that are widely used in areas such as longitudinal studies, genome-wide association studies, and spatial statistics. Since the random effects cannot be integrated out of GLMMs analytically, we approximate the integrated likelihood function using a pseudo-likelihood approach. Our Bayesian approach assumes a flat prior for the fixed effects and includes both approximate reference prior and half-Cauchy prior choices for the variances of random effects. Since the flat prior on the fixed effects is improper, we develop a fractional Bayes factor approach to obtain posterior probabilities of the several competing models. Simulation studies with Poisson GLMMs with spatial random effects and overdispersion random effects show that our approach performs favorably when compared to widely used competing Bayesian methods including deviance information criterion and Watanabe-Akaike information criterion. We illustrate the usefulness and flexibility of our approach with three case studies including a Poisson longitudinal model, a Poisson spatial model, and a logistic mixed model. Our proposed approach is implemented in the R package GLMMselect that is available on CRAN.


Subject(s)
Genome-Wide Association Study , Models, Statistical , Bayes Theorem , Likelihood Functions , Linear Models , Computer Simulation
6.
Altern Ther Health Med ; 28(6): 132-137, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35751897

ABSTRACT

Objective: To detect the expression level of the Mfn2 gene in hepatocellular carcinoma (HCC) and adjacent normal liver tissues and further analyze its anticancer effects. Methods: The expression levels of Mfn2, GLS1 and the autophagy-related proteins lc3b and Beclin1 in liver cancer and adjacent tissues in patients with liver cancer were detected by real-time-quantitative polymerase chain reaction (RT-qPCR). The HepG2 human HCC cell line was cultured in vitro, and the Mfn2 protein was stably expressed through transfection of a high Mfn2 expression plasmid. The Cell-Counting Kit-8 (CCK-8) method was used to observe the effect of Mfn2 overexpression on the activity of HepG2 cells. Furthermore, RT-qPCR and Western blotting were performed to detect the effects of Mfn2 overexpression on the protein expression of GLS1, Beclin1 and lc3b. Results: Compared with tissues adjacent to cancer tissues, the mRNA levels of Mfn2, GLS1, Beclin1 and lc3b in liver cancer tissues were lower. Compared with normal hepatocytes, the expression of Mfn2, Beclin1 and lc3b in HCC cells was decreased, but the expression of GLS1 was increased. Compared with the control group (NC) transfected with empty plasmid, Mfn2 overexpression led to significant time-dependent inhibition of HepG2 cell activity and GLS1 protein expression (P < .05). In addition, Mfn2 overexpression induced autophagy by triggering the expression of autophagy-related proteins Beclin-1 and lc3b in HCC cells (all P < .05). The effect of transfection with a high-dose Mfn2 plasmid was more obvious than that of transfection with a low-dose Mfn2 plasmid (all P < .05). Conclusions: The expression of Mfn2, GLS1, Beclin1 and lc3b in HCC was lower than in normal liver tissue. The expression of Mfn2, Beclin1 and lc3b in HCC cells was decreased, but the expression of GLS1 was increased. Overexpression of Mfn2 inhibited GLS1 gene expression by inhibiting the activity of HCC cells and promoted the expression of Beclin1 and lc3b to induce autophagy, thereby exerting an anticancer effect. Further research is needed to clarify the mechanism of Mfn2 activity.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Autophagy/genetics , Beclin-1/genetics , Beclin-1/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , GTP Phosphohydrolases/genetics , Gene Expression , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mitochondrial Proteins/genetics
7.
J Biol Chem ; 293(32): 12535-12541, 2018 08 10.
Article in English | MEDLINE | ID: mdl-29934308

ABSTRACT

Farnesoid X receptor (FXR) is a member of the family of ligand-activated nuclear receptors. FXR plays critical roles in maintaining many metabolic pathways, including bile acid regulation and glucose and lipid homeostasis, and forms a heterodimeric complex with the retinoid X receptor (RXR). Despite the important roles of the FXR/RXR heterodimerization in human physiology, the molecular basis underlying the FXR/RXR interaction is still uncertain in the absence of a complex structure. Here, we report the heterodimeric structure of FXR and RXR in the presence of an FXR agonist (WAY-362450), RXR agonist (9-cis-retinoic acid), and a peptide derived from a steroid receptor coactivator (SRC2), revealing both unique and conserved modes for FXR heterodimerization. We found that the dimerization with RXR induced allosteric conformational changes on the coactivator-binding site of FXR. These changes enhanced the transcriptional activity of FXR by promoting the coactivator binding, thus suggesting a structural basis for the functional permissiveness of the FXR/RXR heterodimer complex. Furthermore, sequence analyses together with functional mutagenesis studies indicated that the helix H10 largely responsible for the dimerization is highly conserved and also critical for the FXR transcriptional activity. Our findings highlight the important roles of RXR heterodimerization in the nuclear receptor signaling, providing a potential framework to develop pharmaceutical agents in treating FXR/RXR-related diseases.


Subject(s)
Protein Multimerization , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/metabolism , Retinoid X Receptors/chemistry , Retinoid X Receptors/metabolism , Binding Sites , Crystallography, X-Ray , HEK293 Cells , Humans , Protein Binding , Protein Conformation
8.
Biochim Biophys Acta Gen Subj ; 1862(10): 2261-2270, 2018 10.
Article in English | MEDLINE | ID: mdl-30048741

ABSTRACT

BACKGROUND: The 1,4-dihydropyridines (DHPs) are one of the most frequently prescribed classes of antihypertensive monotherapeutic agents worldwide. In addition to treating hypertension, DHPs also exert other beneficial effects, including hepatoprotective effects. However, the mechanism underlying the hepatoprotection remains unclear. METHODS: Biochemical AlphaScreen and cell-based reporter assays were employed to detect the activities of DHPs towards FXR. A crystallographic analysis was adopted to study the binding modes of four DHPs in complex with FXR. Acetaminophen (APAP)-treated wild-type and FXR knockout mice were used to investigate the functional dependence of the effects of the selected DHPs on FXR. RESULTS: A series of DHPs were uncovered as FXR ligands with different activities for FXR, suggesting FXR might serve as an alternative drug target for DHPs. The structural analysis illustrated the specific three-blade propeller binding modes of four DHPs to FXR and explained the detailed mechanisms by which DHPs bind to and are recognized by FXR. The results in mice demonstrated that cilnidipine protected the liver from APAP-induced injury in an FXR-dependent manner. CONCLUSIONS: This study reports the crystal structures of FXR in complex with four DHPs, and confirms that DHPs exert hepatoprotection by targeting FXR. GENERAL SIGNIFICANCE: Our research not only reveals valuable insight for the design and development of next-generation Ca2+ blocker drugs to provide safer and more effective treatments for cardiovascular disorders but also provides a novel and safe structural template for the development of drugs targeting FXR. Moreover, DHPs might be potentially repurposed to treat FXR-mediated diseases other than hypertension.


Subject(s)
Antihypertensive Agents/pharmacology , Calcium Channel Blockers/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Dihydropyridines/pharmacology , Liver/drug effects , RNA-Binding Proteins/physiology , Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Animals , Antihypertensive Agents/chemistry , Calcium Channel Blockers/chemistry , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Dihydropyridines/chemistry , HEK293 Cells , Humans , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Knockout , Models, Molecular , Protein Conformation , RNA-Binding Proteins/chemistry
9.
Pak J Pharm Sci ; 30(5(Special)): 1883-1888, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29084661

ABSTRACT

Molecular targeted antitumor drugs is a major progress in recent years, these drugs usually target specific molecules to tumor cell signaling pathways, reduce toxicity, and can achieve individualized treatment. In this study, we screened three polypeptide proteins by yeast two hybrid systems, which could inhibit tumor growth obviously. The results of this study are expected to further develop new antitumor drugs. Moreover, by using contrast-enhanced computed tomography (CECT) imaging, this study proposes an algorithm for the computer-aided diagnosis (CAD) and classification of adrenal tumors. The experimental results demonstrate an excellent classification performance of this algorithm. Therefore, the method proposed in this paper may accurately locate and qualitatively diagnose the adrenal tumor in an effective manner, thereby providing important references for treatment.


Subject(s)
Adrenal Gland Neoplasms/classification , Adrenal Gland Neoplasms/diagnosis , Molecular Targeted Therapy/methods , Peptides/pharmacology , S-Phase Kinase-Associated Proteins/drug effects , Tomography, X-Ray Computed/methods , Algorithms , Cell Line, Tumor , Cell Proliferation/drug effects , Diagnosis, Computer-Assisted/methods , Humans , Peptides/chemical synthesis
10.
Pak J Pharm Sci ; 30(3(Special)): 1165-1171, 2017 May.
Article in English | MEDLINE | ID: mdl-28671101

ABSTRACT

This paper based on the theory of radiopharmaceuticals and the theory of radiation risk prediction, the author mainly studies the dose distribution of F-FDG and its radiation risk. Through the assessment of the risk of radiation carcinogenesis, the effective dose range was 4.61mSv to 8.97mSv, and the range of radiation carcinogenic risk was 1.57 ×10-3-3.14×10-3. Also, we reviewed the development trend of medical image processing techniques, and the development of medical imaging processing in three-dimensional (3D) medical imaging visualization and PACS-based medical imaging compression is introduced.


Subject(s)
Carcinogenesis/radiation effects , Diagnostic Imaging/methods , Fluorodeoxyglucose F18/adverse effects , Image Processing, Computer-Assisted/methods , Lung Neoplasms/diagnostic imaging , Radiation Dosage , Adult , Aged , Aged, 80 and over , Female , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Male , Middle Aged , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/toxicity , Tissue Distribution
11.
Pain Med ; 17(2): 220-9, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26361083

ABSTRACT

OBJECTIVE: Heme oxygenase-1 (HO-1) exerts protective effects against ischemia and inflammation in the central nervous system. However, its role in neuropathic pain is still unclear. This study was undertaken to explore the distribution and possible mechanism of HO-1 in a mouse model of peripheral nerve injury. DESIGN AND METHODS: The experiment was conducted using a mouse model of L5 spinal nerve ligation (SNL). Mice received repeated intraperitoneal injection of Carbon monoxide-releasing molecule-2 (CO-RM-2), HO-1 inducer cobalt protoporphyrin IX (CoPP) or single intraspinal injection of lentivirus (LV) over-expressing HO-1. The behavior analyses were conducted. The distribution and expression of HO-1 in the spinal cord were analyzed. RESULTS: HO-1 but not HO-2 was upregulated in spinal cord microglia cells after nerve injury, and the repeated intraperitoneal administration of CORM-2 (10 mg/kg/d) or CoPP (5 mg/kg/d) both significantly reduced the mechanical allodynia and thermal hyperalgesia induced by SNL (P < 0.01). Intraspinal injection of LV-HO-1 persistently suppresses SNL-induced neuropathic pain (P < 0.01 or P < 0.05), significantly induced the spinal HO-1 protein content (P < 0.01) and inhibited the microglia activation (P < 0.01) 7 days after SNL. CONCLUSION: HO-1 upregulation could elicit potent analgesic effects against neuropathic pain, which might partly be attributed to inhibition of spinal microglia activation. HO-1 signaling pathway may present a novel strategy for the treatment of neuropathic pain.


Subject(s)
Disease Models, Animal , Heme Oxygenase-1/biosynthesis , Membrane Proteins/biosynthesis , Neuralgia/enzymology , Neuralgia/prevention & control , Pain Measurement/methods , Spinal Nerves/enzymology , Animals , Ligation/adverse effects , Male , Mice , Microglia/enzymology , Microglia/pathology , Neuralgia/pathology , Spinal Nerves/injuries , Spinal Nerves/pathology
12.
J Sep Sci ; 37(22): 3299-305, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25168645

ABSTRACT

Through the use of a homemade sol-gel-derived fiber, a headspace solid-phase microextraction technique coupled to gas chromatography with mass spectrometry was developed for the determination of fatty acids with long, even-numbered carbon chains (C12 -C24 ) in soil samples. The experimental parameters such as reaction time, temperature, and ionic strength that might affect derivatization, extraction, and desorption were investigated. Under the optimized conditions, the linearity of the method ranged from 0.1 to 100 mg/L with a correlation coefficient >0.997. The limit of detection values based on a signal-to-noise ratio of 3:1 were determined with the concentration from 0.39 to 39.4 µg/L. The recoveries of the method for the soil samples were from 91.15 to 108.1%. This developed method using a homemade fiber showed a higher sensitivity than that using a commercial polydimethylsiloxane fiber and was also for the analysis of real soil samples from the Paomaling geological park of China.


Subject(s)
Carbon/chemistry , Fatty Acids/chemistry , Gas Chromatography-Mass Spectrometry , Soil Pollutants/analysis , Soil/chemistry , Solid Phase Microextraction , China , Chromatography, Gas , Dimethylpolysiloxanes/chemistry , Ions , Limit of Detection , Phase Transition , Reproducibility of Results , Signal-To-Noise Ratio , Temperature
13.
Histol Histopathol ; : 18716, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38353136

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent stromal cells that can be derived from a wide variety of human tissues and organs. They can differentiate into a variety of cell types, including osteoblasts, adipocytes, and chondrocytes, and thus show great potential in regenerative medicine. Traumatic brain injury (TBI) is an organic injury to brain tissue with a high rate of disability and death caused by an external impact or concussive force acting directly or indirectly on the head. The current treatment of TBI mainly includes symptomatic, pharmacological, and rehabilitation treatment. Although some efficacy has been achieved, the definitive recovery effect on neural tissue is still limited. Recent studies have shown that MSC therapies are more effective than traditional treatment strategies due to their strong multi-directional differentiation potential, self-renewal capacity, and low immunogenicity and homing properties, thus MSCs are considered to play an important role and are an ideal cell for the treatment of injurious diseases, including TBI. In this paper, we systematically reviewed the role and mechanisms of MSCs and MSC-derived exosomes in the treatment of TBI, thereby providing new insights into the clinical applications of MSCs and MSC-derived exosomes in the treatment of central nervous system disorders.

14.
Open Med (Wars) ; 19(1): 20240968, 2024.
Article in English | MEDLINE | ID: mdl-38799254

ABSTRACT

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro. The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs' therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

15.
Syst Biol Reprod Med ; 70(1): 131-138, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38833557

ABSTRACT

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.


Subject(s)
Gonadotropin-Releasing Hormone , Animals , Male , Gonadotropin-Releasing Hormone/immunology , Rats , Testis/drug effects , Testosterone/blood , Rats, Sprague-Dawley , Immunization
16.
J Proteomics ; 301: 105183, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38688390

ABSTRACT

Puberty is considered a prerequisite for affecting reproductive performance and productivity. Little was known about molecular changes in pubertal goat ovaries. Therefore, we measured and performed a correlation analysis of the mRNA and proteins changes in the pre-pubertal and pubertal goat ovaries. The results showed that only six differentially expressed genes and differentially abundant proteins out of 18,139 genes and 7550 proteins quantified had significant correlations. CNTN2 and THBS1, discovered in the mRNA-mRNA interaction network, probably participated in pubertal and reproductive regulation by influencing GnRH receptor signals, follicular development, and ovulation. The predicted core transcription factors may either promote or inhibit the expression of reproductive genes and act synergistically to maintain normal reproductive function in animals. The interaction between PKM and TIMP3 with other proteins may impact animal puberty through energy metabolism and ovarian hormone secretion. Pathway enrichment analyses revealed that the co-associated key pathways between ovarian genes and proteins at puberty included calcium signalling pathway and olfactory transduction. These pathways were associated with gonadotropin-releasing hormone synthesis and secretion, signal transmission, and cell proliferation. In summary, these results enriched the potential molecules and signalling pathways that affect puberty and provided new insights for regulating and promoting the onset of puberty. SIGNIFICANCE: This study conducted the first transcriptomic and proteomic correlation analysis of pre-pubertal and pubertal goat ovaries and identified six significantly correlated molecules at both the gene and protein levels. Meanwhile, we were drawn to several molecules and signalling pathways that may play a regulatory role in the onset of puberty and reproduction by influencing reproductive-related gene expression, GnRH receptor signals, energy metabolism, ovarian hormone secretion, follicular development, and ovulation. This information contributed to identify potential biomarkers in pubertal goat ovaries, which was vital for predicting the onset of puberty and improving livestock performance.


Subject(s)
Goats , Ovary , Proteomics , Sexual Maturation , Animals , Female , Goats/genetics , Sexual Maturation/physiology , Ovary/metabolism , Proteomics/methods , Gene Expression Profiling , Transcriptome
17.
J Vet Med Sci ; 86(5): 497-506, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38479882

ABSTRACT

The study aimed to investigate the effect of Grid1, encoding the glutamate ionotropic receptor delta type subunit 1 (GluD1), on puberty onset in female rats. Grid1 mRNA and protein expression was detected in the hypothalamus of female rats at prepuberty and puberty. The levels of Grid1 mRNA in the hypothalamus, the fluorescence intensity in the arcuate nucleus and paraventricular nucleus of the prepubertal rats was significantly lower than pubertal. Additionally, the expression of Grid1 was suppressed in primary hypothalamus cells and prepubertal rat. Finally, investigated the effect of Grid1 knockdown on puberty onset and reproductive performance. Treatment of hypothalamic neurons with LV-Grid1 decreased the level of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3) mRNA expression, but increased the Gnrh (encoding gonadotropin-releasing hormone) mRNA levels. After an ICV injection, the time for the rat vaginal opening occurred earlier. Moreover, Gnrh mRNA expression was increased, whereas Rfrp-3 mRNA expression was decreased in the hypothalamus. The concentration of progesterone (P4) in the serum was significantly decreased compare with control group. Ovary hematoxylin-eosin staining revealed that the LV-Grid1 group mainly contained primary and secondary follicles. The reproductive performance of the rats was not affected by the Grid1 knockdown. Therefore, Grid1 may affect the onset of puberty in female rats by regulating the levels of Gnrh, and Rfrp-3 in the hypothalamus, as well as the concentrations of P4, but not reproduction performance.


Subject(s)
Gonadotropin-Releasing Hormone , Hypothalamic Hormones , Hypothalamus , Sexual Maturation , Animals , Female , Rats , Gonadotropin-Releasing Hormone/metabolism , Gonadotropin-Releasing Hormone/genetics , Hypothalamus/metabolism , Neurons/metabolism , Neuropeptides/metabolism , Neuropeptides/genetics , Progesterone/blood , Progesterone/metabolism , Rats, Sprague-Dawley , RNA, Messenger/metabolism , RNA, Messenger/genetics , Sexual Maturation/physiology
18.
Technol Cancer Res Treat ; 22: 15330338231167732, 2023.
Article in English | MEDLINE | ID: mdl-37050886

ABSTRACT

BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.


Subject(s)
Neoplasm Proteins , Precancerous Conditions , Humans , Neoplasm Proteins/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Lung/metabolism , Salivary Glands/metabolism , Precancerous Conditions/genetics , Cell Line, Tumor , Epithelial-Mesenchymal Transition , Cell Movement
19.
Article in English | MEDLINE | ID: mdl-36901525

ABSTRACT

Based on the related environmental data of Chengdu and Chongqing from 2011 to 2020, this paper constructs a multivariate environment performance evaluation system, combines the self-built indicator system determination criteria and rules, evaluates and compares the environmental performance of Chengdu and Chongqing, and also discusses the impact of COVID-19 on urban environmental performance. The research results show that the overall environmental performance increased from 2011 to 2020, but there are differences between different subsystems, mainly manifested in the best water environment performance, followed by air environment and solid waste; moreover, the noise environment maintains a relatively stable level. By comparing the average levels of various subsystems of the Chengdu-Chongqing dual cities from 2011 to 2020, it can be seen that Chengdu City has better environmental performance in air environment and solid waste, while Chongqing City has better environmental performance in the water environment and noise environment. In addition, this paper also found that the impact of the epidemic on urban environmental performance mainly comes from the impact on the air environment. At present, the overall environmental performance of the two places has shown a trend of environmentally coordinated development. In the future, Chengdu and Chongqing should further optimize and improve their relatively weak environmental subsystems, deepen the joint action mechanism between the two places, and build a green and high-quality development economic circle for the Chengdu-Chongqing twin cities.


Subject(s)
COVID-19 , Solid Waste , Humans , Cities , China , Water
20.
Front Surg ; 10: 1126596, 2023.
Article in English | MEDLINE | ID: mdl-37325414

ABSTRACT

Background: Primary palmar hyperhidrosis (PPH) is a condition marked by an overactive secretion of the hand's exocrine glands and is frequently hereditary. The profuse sweating associated with this condition can significantly impair the patient's daily activities and quality of life. Objective: The objective of this study was to compared the benefits and drawbacks of thoracic sympathetic block and thoracic sympathetic radiofrequency in the treatment of PPH. Methods: A retrospective analysis was conducted on 69 patients. They were divided into groups A and B according to their treatment. Group A (34 cases) received CT-guided percutaneous thoracic sympathetic nerve chain anhydrous alcohol chemical damage block, and group B (35 cases) received CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency thermocoagulation. Results: Palmar sweating disappeared immediately after the operation. The recurrence rates at 1, 3, 6, 12, 24, and 36 months were 5.88% vs. 2.86% (P > 0.05), 20.59% vs. 5.71% (P > 0.05), 32.35% vs. 11.43% (P < 0.05),32.35% vs. 11.43% (P < 0.05), 25% vs. 14.71% (P < 0.05), and 68.75% vs. 20.59% (P < 0.05), respectively. The incidence of intercostal neuralgia and compensatory hyperhidrosis was higher in group A compared with of group B (52.94% vs. 22.86%, P < 0.05; 55.88% vs. 22.86%, P < 0.05). Conclusion: Both methods were found to be effective in treating PPH, but thoracic sympathetic radiofrequency had a longer-term effect, a lower recurrence rate, and a lower incidence of intercostal neuralgia and compensatory hyperhidrosis than a thoracic sympathetic block.

SELECTION OF CITATIONS
SEARCH DETAIL