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1.
Front Plant Sci ; 15: 1389154, 2024.
Article in English | MEDLINE | ID: mdl-38872885

ABSTRACT

With the rapid advances in next-generation sequencing technology, numerous non-protein-coding transcripts have been identified, including long noncoding RNAs (lncRNAs), which are functional RNAs comprising more than 200 nucleotides. Although lncRNA-mediated regulatory processes have been extensively investigated in animals, there has been considerably less research on plant lncRNAs. Nevertheless, multiple studies on major crops showed lncRNAs are involved in crucial processes, including growth and development, reproduction, and stress responses. This review summarizes the progress in the research on lncRNA roles in several major crops, presents key strategies for exploring lncRNAs in crops, and discusses current challenges and future prospects. The insights provided in this review will enhance our comprehension of lncRNA functions in crops, with potential implications for improving crop genetics and breeding.

2.
J Parkinsons Dis ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38848196

ABSTRACT

Background: Gait disturbance is a vital characteristic of motor manifestation in α- synucleinopathies, especially Parkinson's disease. Subtle gait alterations are present in isolated rapid eye movement sleep behavior disorder (iRBD) patients before phenoconversion; it is yet unclear, if gait analysis may predict phenoconversion. Objective: To investigate subtle gait alterations and explore whether gait analysis using wearable sensors is associated with phenoconversion of iRBD to α-synucleinopathies. Methods: Thirty-one polysomnography-confirmed iRBD patients and 33 healthy controls (HCs) were enrolled at baseline. All participants walked for a minute while wearing 6 inertial sensors on bilateral wrists, ankles, and the trunk (sternal and lumbar region). Three conditions were tested: (i) normal walking, (ii) fast walking, and (iii) dual-task walking. Results: Decreased arm range of motion and increased gait variation (stride length, stride time and stride velocity) discriminate converters from HCs at baseline. After an average of 5.40 years of follow-up, 10 patients converted to neurodegenerative diseases (converters). Cox regression analysis showed higher value of stride length asymmetry under normal walking condition to be associated with an early conversion of iRBD to α- synucleinopathies (adjusted HR 4.468, 95% CI 1.088- 18.349, p = 0.038). Conclusions: Stride length asymmetry is associated with progression to α- synucleinopathies in patients with iRBD. Gait analysis with wearable sensors may be useful for screening, monitoring, and risk stratification for disease-modifying therapy trials in patients with iRBD.

3.
BMC Genomics ; 25(1): 534, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816794

ABSTRACT

BACKGROUND: Maedi-visna virus (MVV) is a lentivirus that infects monocyte/macrophage lineage cells in sheep, goats, and wild ruminants and causes pneumonia, mastitis, arthritis, and encephalitis. The immune response to MVV infection is complex, and a complete understanding of its infection and pathogenesis is lacking. This study investigated the in vivo transcriptomic patterns of lung tissues in sheep exposed to MVV using the RNA sequencing technology. RESULT: The results indicated that 2,739 genes were significantly differentially expressed, with 1,643 downregulated genes and 1,096 upregulated genes. Many variables that could be unique to MVV infections were discovered. Gene Ontology analysis revealed that a significant proportion of genes was enriched in terms directly related to the immune system and biological responses to viral infections. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the most enriched pathways were related to virus-host cell interactions and inflammatory responses. Numerous immune-related genes, including those encoding several cytokines and interferon regulatory factors, were identified in the protein-protein interaction network of differentially expressed genes (DEGs). The expression of DEGs was evaluated using real-time polymerase chain reaction and western blot analysis. CXCL13, CXCL6, CXCL11, CCR1, CXCL8, CXCL9, CXCL10, TNFSF8, TNFRSF8, IL7R, IFN-γ, CCL2, and MMP9 were upregulated. Immunohistochemical analysis was performed to identify the types of immune cells that infiltrated MVV-infected tissues. B cells, CD4+ and CD8+ T cells, and macrophages were the most prevalent immune cells correlated with MVV infection in the lungs. CONCLUSION: Overall, the findings of this study provide a comprehensive understanding of the in vivo host response to MVV infection and offer new perspectives on the gene regulatory networks that underlie pathogenesis in natural hosts.


Subject(s)
Lung , Visna-maedi virus , Animals , Visna-maedi virus/genetics , Lung/virology , Lung/immunology , Lung/pathology , Sheep , Gene Expression Profiling , Transcriptome , Pneumonia, Progressive Interstitial, of Sheep/genetics , Pneumonia, Progressive Interstitial, of Sheep/virology , Pneumonia, Progressive Interstitial, of Sheep/immunology , Protein Interaction Maps , Gene Expression Regulation , Gene Ontology
4.
Nat Commun ; 15(1): 4301, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773089

ABSTRACT

The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent DNA prime-protein boost HIV vaccine. HmAb64 is derived from heavy chain variable germline gene IGHV1-18 and light chain germline gene IGKV1-39. It has a third heavy chain complementarity-determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 20 (10%), including tier-2 strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 in complex with a CNE40 SOSIP trimer revealed details of its recognition; HmAb64 uses both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4bs. This study demonstrates that a gp120-based vaccine can elicit antibodies capable of tier 2-HIV neutralization.


Subject(s)
AIDS Vaccines , Antibodies, Neutralizing , CD4 Antigens , HIV Antibodies , HIV-1 , Humans , AIDS Vaccines/immunology , HIV-1/immunology , HIV Antibodies/immunology , Antibodies, Neutralizing/immunology , CD4 Antigens/immunology , CD4 Antigens/metabolism , Vaccines, DNA/immunology , Antibodies, Monoclonal/immunology , HIV Infections/prevention & control , HIV Infections/immunology , HIV Infections/virology , Cryoelectron Microscopy , HIV Envelope Protein gp120/immunology , HIV Envelope Protein gp120/chemistry , Binding Sites , Complementarity Determining Regions/immunology , Complementarity Determining Regions/chemistry
5.
Food Sci Biotechnol ; 33(7): 1685-1696, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38623439

ABSTRACT

American ginseng (Panax quinquefolium L.) is used as tonic plant and high-grade nourishment. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was established for identifying the chemical constituent in three morphological regions of American ginseng, including main root (MR), rhizome (RH) and lateral root (LR). The 63 saponins was identified in different morphological regions of 10 American ginseng samples. The chemical maker compounds in corresponding morphological region, while the major compounds of MR (malonyl-ginsenoside Rb1, ginsenoside Rd, Rs2 and pseudo-RC1), LR (stipuleanoside R2, ginsenoside Re and malonyl-ginsenoside Rc), and RH (malonyl-ginsenoside Rd, Rb3, and chikusetsu saponin II) were discovered. Correlation analysis showed that 11 compounds were positively correlated with the antioxidant activity of American ginseng. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01453-4.

6.
Mov Disord ; 39(5): 847-854, 2024 May.
Article in English | MEDLINE | ID: mdl-38477228

ABSTRACT

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F-9-fluoropropyldihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.


Subject(s)
Corpus Striatum , Parkinson Disease , Supranuclear Palsy, Progressive , Vesicular Monoamine Transport Proteins , Humans , Supranuclear Palsy, Progressive/diagnostic imaging , Supranuclear Palsy, Progressive/metabolism , Male , Female , Aged , Middle Aged , Vesicular Monoamine Transport Proteins/metabolism , Corpus Striatum/metabolism , Corpus Striatum/diagnostic imaging , Parkinson Disease/metabolism , Parkinson Disease/diagnostic imaging , Positron-Emission Tomography/methods , Tetrabenazine/analogs & derivatives , Substantia Nigra/diagnostic imaging , Substantia Nigra/metabolism , Substantia Nigra/pathology , Positron Emission Tomography Computed Tomography/methods
7.
Virology ; 594: 110059, 2024 06.
Article in English | MEDLINE | ID: mdl-38518442

ABSTRACT

Ovine pulmonary adenocarcinoma (OPA), caused by the jaagsiekte sheep retrovirus (JSRV), is a chronic, progressive, and contagious lung tumor that seriously affects sheep production. It also represents a valuable animal model for several human lung adenocarcinomas. However, little is known about the role of autophagy in OPA tumorigenesis. Here, Western blotting combined with transmission electron microscopy examination and Cyto-ID dye staining was employed for evaluation of changes of autophagic levels. The results of the present study showed that expression of the autophagy marker proteins Beclin-1 and LC3 was decreased in OPA lung tissues, as well as in cells overexpressing the envelope glycoprotein of JSRV (JSRV Env). Reduced numbers of autophagosomes were also observed in cells overexpressing JSRV Env, although assessment of autophagic flux showed that JSRV Env overexpression did not block the formation of autophagosomes, suggesting increased degradation of autolysosomes. Last, mouse xenograft experiments indicated that inhibition of autophagy by 3-methyladenine suppressed both tumor growth and the epithelial-to-mesenchymal transition. In conclusion, JSRV, through JSRV Env, takes advantage of the autophagy process, leading to the development of OPA.


Subject(s)
Jaagsiekte sheep retrovirus , Sheep , Animals , Humans , Mice , Jaagsiekte sheep retrovirus/genetics , Jaagsiekte sheep retrovirus/metabolism , Gene Products, env , Cell Transformation, Neoplastic , Autophagy , Glycoproteins/metabolism
8.
Endocrine ; 84(1): 236-244, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38206435

ABSTRACT

BACKGROUND: Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. OBJECTIVE: This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. METHOD: 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum ß-isomer of C-terminal telopeptides of type I collagen (ß-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. RESULTS: Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. CONCLUSION: All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.


Subject(s)
Osteoporosis, Postmenopausal , Osteoporosis , Female , Humans , Beijing/epidemiology , Bone Density/physiology , Muscles , Osteocalcin , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/epidemiology , Postmenopause
9.
Parkinsonism Relat Disord ; 120: 105979, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38241952

ABSTRACT

INTRODUCTION: The motor subtypes of Parkinson's disease (PD) are widely accepted and implemented. However, the motor subtypes have been thought to represent different stages of PD recently because some patients experience tremor-dominant (TD) conversion to the non-tremor-dominant subtype, such as postural instability-gait difficulty (PIGD). In this study, we explore the monoaminergic denervation features of the striatal and extra-striatal areas in patients with different subtypes of PD with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ) PET/CT. METHODS: Sixty-five patients diagnosed with PD were included and classified as TD (n = 25) and PIGD (n = 40). We evaluated the difference of monoaminergic features of each subregion of brain between motor subtypes of PD, as well as associations between these features and Parkinsonian motor symptoms. RESULTS: The striatal standardized uptake value ratios (SUVR) showed that dopaminergic disruption of patients with PIGD was more symmetrical in the posterior ventral putamen (p < 0.001) and more severe in the ipsilateral posterior dorsal putamen (p < 0.001 corrected) compared with that of patients with TD. The severity of PIGD scores was associated with striatal dopaminergic depletion, while tremor was associated with monoaminergic changes in extra-striatal areas, including pallidus, thalamus, and raphe nuclie. CONCLUSION: These results indicate that patients with different motor subtypes may have different underlying mechanisms of PD pathogenesis. Therefore, accurate diagnosis of PD subtypes can aid prognosis evaluation and treatment decision-making.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Tremor/etiology , Tremor/complications , Positron Emission Tomography Computed Tomography/adverse effects , Putamen/diagnostic imaging , Putamen/pathology , Brain/pathology , Dopamine
10.
Medicine (Baltimore) ; 102(49): e36576, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38065884

ABSTRACT

BACKGROUND: Heart failure (HF) is the most common cardiovascular disease in clinics. Processed Panax ginseng C.A. Mey. Products have significant therapeutic effects on HF. Therefore, it is of great significance to explore the mechanism of action of Processed Panax ginseng C.A. Mey. Products in the treatment of HF. METHODS: The saponin-like constituents of 3 different ginseng preparations were characterized by UPLC/QE-MS and the identified saponin constituents were subjected to network pharmacological analysis. Protein-protein interaction analyses of the targets of different ginseng preparations for the treatment of heart failure (HF) were performed using the STRING database, Gene Ontology enrichment analyses and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the DAVID database, and the results of the network pharmacological analyses were validated using the Autodock software. Finally, the relative quantitative content of 5 major ginsenosides in 3 processed ginseng products was evaluated. RESULTS: A total of 40 saponin compounds were identified based on mass spectrometry data. Network pharmacology and molecular docking analyses were used to predict the major targets of these sapions compounds and the key pathways mediating their anti-HF effects. After conducting a thorough screening, the study identified 5 primary ingredients of ginseng products ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rk1, ginsenoside Rg5, and ginsenoside CK that can potentially target 22 essential proteins: EGFR, AKT1, ERBB2, STAT3, TNF, ESR1, MTOR, HRAS, MMP9, and PIK3CA, etc. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ginseng products can be beneficial in treating HF by interacting with pathways such as the PI3K-Akt signaling pathway, the TNF signaling pathway, the mTOR signaling pathway, and others. CONCLUSION: The present study revealed that the treatment of HF with different processed ginseng products may be related to the regulation of the PI3K-Akt signaling pathway, TNF signaling pathway, apoptosis pathway, mTOR signaling pathway, etc, and that the key active ingredients may be concentrated in black ginseng, which provides a theoretical basis and direction for the further study of the mechanism of action of ginseng. This provides a theoretical basis and research direction for further in-depth study of its mechanism of action.


Subject(s)
Drugs, Chinese Herbal , Heart Failure , Panax , Saponins , Humans , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Heart Failure/drug therapy , TOR Serine-Threonine Kinases , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
11.
ACS Omega ; 8(45): 43285-43294, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-38024707

ABSTRACT

Rare ginsenosides with major pharmacological effects are barely present in natural ginseng and are required to be obtained by transformation. In the current study, ginsenoside Rb1 was chemically transformed with the involvement of ethanol molecules to prepare rare ginsenosides using the synthesized heterogeneous catalyst 12-HPW@MeSi. A total of 16 transformation products were obtained and identified using high-performance liquid chromatography coupled with multistage tandem mass spectrometry and high-resolution mass spectrometry. Ethanol molecules were involved in the production of 6 transformation products by adding to the C-20(21), C-20(22), or C-24(25) double bonds on the aglycone to produce ethoxyl groups at the C-25 and C-20 positions. Transformation pathways of ginsenoside Rb1 are summarized, which involve deglycosylation, elimination, cycloaddition, epimerization, and addition reactions. In addition, 12-HPW@MeSi was recyclable through a simple centrifugation, maintaining an 85.1% conversion rate of Rb1 after 3 cycles. This work opens up an efficient and recycled process for the preparation of rare ginsenosides with the involvement of organic molecules.

12.
Front Immunol ; 14: 1281051, 2023.
Article in English | MEDLINE | ID: mdl-37854598

ABSTRACT

[This corrects the article DOI: 10.3389/fimmu.2023.1164667.].

13.
Res Sq ; 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37886518

ABSTRACT

The vaccine elicitation of HIV-neutralizing antibodies with tier-2-neutralization breadth has been a challenge. Here, we report the isolation and characteristics of a CD4-binding site specific monoclonal antibody, HmAb64, from a human volunteer immunized with a polyvalent gp120 DNA prime-protein boost vaccine. HmAb64 derived from heavy chain variable germline gene IGHV1-18, light chain germline gene IGKV1-39, and had a 3rd heavy chain complementarity determining region (CDR H3) of 15 amino acids. On a cross-clade panel of 208 HIV-1 pseudo-virus strains, HmAb64 neutralized 21 (10%), including tier-2 neutralization resistant strains from clades B, BC, C, and G. The cryo-EM structure of the antigen-binding fragment of HmAb64 bound to a conformation between prefusion closed and occluded open forms of envelope trimer, using both heavy and light CDR3s to recognize the CD4-binding loop, a critical component of the CD4-binding site. A gp120 subunit-based vaccine can thus elicit an antibody capable of tier 2-HIV neutralization.

14.
J Pharm Biomed Anal ; 236: 115738, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37742504

ABSTRACT

OBJECTIVE: This study aimed to explore the mechanism of total saponin of black ginseng (TSBG) in treating heart failure (HF) in DOX-induced HF model rats. METHODS: Rats with HF induced by the intraperitoneal injection of DOX were treated with TSBG (low dose, 30 mg/kg/day; medium dose, 60 mg/kg/day; high dose, 120 mg/kg/day) and shakubar trivalsartan (80 mg/kg/day, positive control) for four weeks. Serum BNP and ANP levels were tested by ELISA, and pathological tissue sections were examined. Serum metabolites were measured using nontargeted metabolomic techniques. The expression of Akt/mTOR autophagy-associated proteins in heart tissue was detected using Western blot, including Beclin1, p62, LCII and LC3I. RESULTS: Compared with the model group, rats in the TSBG-H group had a significantly lower heart index (p < 0.05), significantly lower serum levels of BNP (p < 0.01) and ANP (p < 0.01) and significantly fewer cardiac histopathological changes. Metabolomic results showed that TSBG significantly back-regulated 12 metabolites (p < 0.05), including cholesterol, histamine, sphinganine, putrescine, arachidonic acid, 3-sulfinoalanine, hypotaurine, gluconic acid and lysoPC (18:0:0). These metabolite changes were involved in taurine and hypotaurine metabolism, arachidonic acid metabolism, sphingolipid metabolism, etc. The protein expression level of p-Akt/Akt and p-mTOR/mTOR was significantly up-regulated (p < 0.001), whereas that of Beclin1, p62 (p < 0.001) and LCII/LC3I was down-regulated (p < 0.05). CONCLUSION: TSBG has an excellent therapeutic effect on DOX-induced HF in rats, probably by regulating the Akt/mTOR autophagy signalling pathway, resulting in the improvement of taurine and hypotaurine metabolism, arachidonic acid metabolism and sphingolipid metabolism, which may provide a reference for elucidating the potential mechanism of action of TSBG against HF.


Subject(s)
Heart Failure , Panax , Saponins , Rats , Animals , Rats, Sprague-Dawley , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/therapeutic use , Saponins/pharmacology , Beclin-1 , Panax/metabolism , Arachidonic Acid , Heart Failure/chemically induced , Heart Failure/drug therapy , TOR Serine-Threonine Kinases/metabolism , Metabolomics , Taurine , Sphingolipids/therapeutic use
15.
Molecules ; 28(15)2023 Jul 25.
Article in English | MEDLINE | ID: mdl-37570602

ABSTRACT

Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. have different clinical efficacies, with the former typically used to treat typhoid fever and the latter mainly used to clear liver heat. The differences in their clinical efficacy are closely related to their complex chemical composition, especially the active components. In this study, the saponins and volatile oils in two varieties of Radix Bupleuri grown in different regions were extracted and analyzed using high-performance liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (MS), and the absolute contents of five saikosaponins were accurately quantified using an established HPLC-MS method in the multiple reaction monitoring mode. Multivariate statistical analysis was performed to reveal the difference in the active components between the two varieties. The saikosaponin content was significantly affected by variety and growing region, with all five saikosaponins being significantly higher in Bupleurum chinense DC. than in Bupleurum scorzonerifolium Willd. The results of principal component analysis and hierarchical cluster analysis show a clear distinction between the two varieties in terms of both saponins and volatile oils. Twenty-one saponins, including saikosaponin b2 and b1, and fifty-two volatile oils, including 2-tetradecyloxirane and chloromethyl cyanide, were screened and identified as differential compounds contributing to the significant difference between the two varieties. These compounds may also be responsible for the difference in clinical efficacy between Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. All the results suggest that the accumulation and diversity of active components in Radix Bupleuri are significantly affected by the variety. In contrast to previous reports, this study provides the absolute contents of five saikosaponins in Radix Bupleuri of different varieties and reduces the influence of the growing region on the analytical results by collecting samples from different regions. The results of this study may provide a reference for the identification and quality evaluation of different varieties of Radix Bupleuri.


Subject(s)
Bupleurum , Oils, Volatile , Oleanolic Acid , Saponins , Bupleurum/chemistry , Chromatography, High Pressure Liquid/methods , Gas Chromatography-Mass Spectrometry , Mass Spectrometry , Saponins/analysis , Oleanolic Acid/analysis , Oils, Volatile/analysis , Plant Roots/chemistry
16.
Mass Spectrom Rev ; 2023 Aug 20.
Article in English | MEDLINE | ID: mdl-37598314

ABSTRACT

Direct analysis in real time (DART) represents a new generation of ionization techniques that are used to rapidly ionize small molecules under ambient environments. The combination of DART with various mass spectrometry (MS) instruments allows analyzing multiple plant materials, including traditional Chinese herbal medicines (TCHMs), under simple or no sample treatment conditions. This review discussed the DART principles, including devices, ionization mechanisms, and operation parameters. Typical spectra detected by DART-MS were exhibited and discussed. Numerous applications of DART-MS in the fields of plant material and TCHM analysis were reviewed, including compound identification, biomarker discovery, fingerprinting analysis, and quantification analysis. Besides, modifications and improvements of DART-MS, such as hyphenated application with other separation methods, laser-based desorption techniques, and online sampling configuration, were summarized as well.

17.
Breast Cancer Res ; 25(1): 62, 2023 06 06.
Article in English | MEDLINE | ID: mdl-37280713

ABSTRACT

BACKGROUND: Although trastuzumab and other HER2-targeted therapies have significantly improved survival in patients with HER2 overexpressed or amplified (HER2+) breast cancer, a significant proportion of patients do not respond or eventually develop clinical resistance. Strategies to reverse trastuzumab resistance remain a high clinical priority. We were the first to report the role of CXCR4 in trastuzumab resistance. The present study aims to explore the therapeutic potential of targeting CXCR4 and better understand the associated mechanisms. METHODS: Immunofluorescent staining, confocal microscopy analysis, and immunoblotting were used to analyze CXCR4 expression. BrdU incorporation assays and flow cytometry were used to analyze dynamic CXCR4 expression. Three-dimensional co-culture (tumor cells/breast cancer-associated fibroblasts/human peripheral blood mononuclear cells) or antibody-dependent cellular cytotoxicity assay was used to mimic human tumor microenvironment, which is necessary for testing therapeutic effects of CXCR4 inhibitor or trastuzumab. The FDA-approved CXCR4 antagonist AMD3100, trastuzumab, and docetaxel chemotherapy were used to evaluate therapeutic efficacy in vitro and in vivo. Reverse phase protein array and immunoblotting were used to discern the associated molecular mechanisms. RESULTS: Using a panel of cell lines and patient breast cancer samples, we confirmed CXCR4 drives trastuzumab resistance in HER2+ breast cancer and further demonstrated the increased CXCR4 expression in trastuzumab-resistant cells is associated with cell cycle progression with a peak in the G2/M phases. Blocking CXCR4 with AMD3100 inhibits cell proliferation by downregulating mediators of G2-M transition, leading to G2/M arrest and abnormal mitosis. Using a panel of trastuzumab-resistant cell lines and an in vivo established trastuzumab-resistant xenograft mouse model, we demonstrated that targeting CXCR4 with AMD3100 suppresses tumor growth in vitro and in vivo, and synergizes with docetaxel. CONCLUSIONS: Our findings support CXCR4 as a novel therapeutic target and a predictive biomarker for trastuzumab resistance in HER2+ breast cancer.


Subject(s)
Breast Neoplasms , Humans , Animals , Mice , Female , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Docetaxel/pharmacology , Apoptosis , Leukocytes, Mononuclear/metabolism , Receptor, ErbB-2/metabolism , Cell Line, Tumor , G2 Phase Cell Cycle Checkpoints , Mitosis , Drug Resistance, Neoplasm , Tumor Microenvironment , Receptors, CXCR4/genetics
18.
J Anim Sci ; 1012023 Jan 03.
Article in English | MEDLINE | ID: mdl-37282598

ABSTRACT

Minks are seasonal breeders whose seminiferous epithelium undergoes regression through massive germ cell death, leaving only Sertoli cells and spermatogonial cells in the tubules. However, the molecular mechanisms that control this biological process remain largely unknown. This study describes a transcriptomic analysis of mink testes at various reproductive stages (active, regressing, and inactive). A comparison of seminiferous epithelium at different stages of reproduction shows that cell adhesion is altered during regression. In addition, genes and proteins involved in forming the blood-testis barrier (BTB) were examined in sexually active and inactive minks. The seminiferous epithelium in the testes of sexually inactive minks expressed occludin, but this expression was not discernibly observed in the testes of sexually active minks. There was no discernible expression of CX43 in the seminiferous epithelium in the testes of sexually inactive minks, but CX43 was expressed in the testes of sexually active minks. During the regression process, we observed a remarkable increase in the expression levels of Claudin-11, which is associated with Sertoli-germ cell junctions. In conclusion, these findings suggest a loss of Sertoli-germ cell adhesion, which may regulate postmeiotic cell shedding during testicular regression in mink.


Here, we report for the first time the molecular mechanisms of testicular regression in mink. Our results, together with studies on other animals' characteristic reproductive features, identify a cluster of events crucial to the seminiferous epithelium regression process in mammalian seasonal breeders and highlight perspectives unique to the mink.


Subject(s)
Mink , Seminiferous Epithelium , Male , Animals , Seminiferous Epithelium/metabolism , Cell Adhesion , Seasons , Connexin 43/metabolism , Testis/metabolism , Sertoli Cells/metabolism
19.
J Agric Food Chem ; 71(25): 9815-9825, 2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37309987

ABSTRACT

Soybean [Glycine max (Linn.) Merr.] is an important oil crop. Long noncoding RNAs (lncRNAs) play a variety of functions in plants. However, their function in the soybean oil synthesis pathway is yet to be uncovered. Here, the lncRNA43234 gene related to soybean oil synthesis was screened, and the full-length cDNA sequence of the lncRNA was obtained using rapid amplification of cDNA ends. Overexpression of lncRNA43234 increased the content of crude protein in seeds, decreased the content of oleic acid, and affected the content of alanine and arginine in free amino acids. RNA interference of the lncRNA43234 gene decreased the crude protein content in seeds. Quantitative real-time polymerase chain reaction analysis revealed that lncRNA43234 influenced the expression of XM_014775786.1 associated with phosphatidylinositol metabolism by acting as a decoy for miRNA10420, thereby affecting the content of soybean oil. Our results provide insights into how lncRNA-mediated competing endogenous RNA regulatory networks are involved in soybean oil synthesis.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Glycine max/chemistry , Soybean Oil/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , DNA, Complementary/analysis , Oleic Acid/metabolism , Seeds/chemistry , MicroRNAs/metabolism , Gene Regulatory Networks
20.
Medicine (Baltimore) ; 102(22): e33773, 2023 Jun 02.
Article in English | MEDLINE | ID: mdl-37266650

ABSTRACT

RATIONALE: Schizophyllum commune (S. commune) is a basidiomycete bracket fungus that rarely causes invasive fungal infections. It is often misdiagnosed as other invasive fungal disease because of its atypical clinical features. Here we report a case of pneumonia due to S commune and review the relevant literature. PATIENT CONCERNS AND DIAGNOSES: A 55-year-old male with a history of diabetes and poor glycemic control presented with cough and sputum for half a month. Laboratory examination showed elevated peripheral blood eosinophils, bronchoalveolar lavage fluid eosinophils and increased serum total immunoglobulin E. Chest computed tomography revealed a gloved finger sign and consolidation in the middle lobe of the right lung and the upper lobe of the left lung. Bronchoscopy revealed thick white mucous plugs in the left lingular bronchus, which could be removed partially by suctioning. The culture of bronchoalveolar lavage fluid and bronchoscopy brush specimens grew cottony white mold in sabouraud dextrose agar. Pneumonia caused by S. commune was diagnosed based on clinical features and microbial methods. INTERVENTIONS AND OUTCOMES: Voriconazole combined with inhaled budesonide and formoterol (inhaled corticosteroids + long-acting ß-2 receptor agonist) were given, and his symptoms improved. The count of peripheral blood eosinophils and serum total immunoglobulin E decreased after 1 month. Repeated chest computed tomography showed remarkable improvement over the previous lesions. LESSONS: Although rarely reported, infections in the lungs caused by S commune should be reminded especially in patients with immunocompromised. This case illustrates the risk factors, clinical symptoms and imaging features of the pneumonia caused by S. commune. It also further highlights the diagnosis and treatment of this disease through reviewing relevant literature.


Subject(s)
Diabetes Mellitus , Pneumonia , Schizophyllum , Male , Humans , Middle Aged , Lung/pathology , Bronchi , Pneumonia/pathology , Diabetes Mellitus/pathology
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