Publications by authors named "Jinhui Wang"

321 Publications

Dual transcriptional profiling of carrot and 'Candidatus Liberibacter solanacearum' at different stages of infection suggests complex host-pathogen interaction.

Mol Plant Microbe Interact 2021 Jul 28. Epub 2021 Jul 28.

University of Helsinki, 3835, Department of Agricultural Sciences, Helsinki, Uusimaa, Finland;

The interactions between the phloem-limited pathogen 'Candidatus Liberibacter solanacearum' (CLso) haplotype C and carrot (Daucus carota subsp. sativus) were studied at 4, 5 and 9 weeks post inoculation (wpi), by combining dual RNA-Seq results with data on bacterial colonization and observations of the plant phenotype. In the infected plants, genes involved in jasmonate biosynthesis, salicylate signaling, PAMP and effector-triggered immunity and production of pathogenesis-related proteins were upregulated. At 4 wpi, terpenoid synthesis-related genes were upregulated, presumably as a response to the psyllid feeding, whereas at 5 and 9 wpi, genes involved in both the terpenoid and flavonoid production were downregulated and phenylpropanoid genes were upregulated. Chloroplast-related gene expression was downregulated, in concordance with the observed yellowing of the infected plant leaves. Both the RNA-Seq data and electron microscopy suggested callose accumulation in the infected phloem vessels, likely to impair the transport of photosynthates, while phloem regeneration was suggested by the formation of new sieve cells and the upregulation of cell wall-related gene expression. The CLso genes involved in replication, transcription and translation were expressed at high levels at 4 and 5 wpi, whereas at 9 wpi the Flp pilus genes were highly expressed, suggesting adherence and reduced mobility of the bacteria. The CLso genes encoding ATP and C4-dicarboxylate uptake were differentially expressed between the early and late infection stages, suggesting a change in the dependence on different host-derived energy sources. HPE1 effector and salicylate hydroxylase were expressed, presumably to suppress host cell death and salicylic acid-dependent defenses during the infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/MPMI-10-20-0274-RDOI Listing
July 2021

Identification and validation of two major QTLs for spike compactness and length in bread wheat (Triticum aestivum L.) showing pleiotropic effects on yield-related traits.

Theor Appl Genet 2021 Jul 26. Epub 2021 Jul 26.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.

Key Message: Two major and stable QTLs for spike compactness and length were detected and validated in multiple genetic backgrounds and environments, and their pleiotropic effects on yield-related traits were analyzed. Spike compactness (SC) and length (SL) are greatly associated with wheat (Triticum aestivum L.) grain yield. To detect quantitative trait loci (QTL) associated with SC and SL, two biparental populations derived from crosses of Chuanmai42/Kechengmai1 and Chuanmai42/Chuannong16 were employed to perform QTL mapping in five environments. A total of 34 QTLs were identified, in which six major QTLs were repeatedly detected in more than four environments and the best linear unbiased prediction datasets, explaining 7.13-33.6% of phenotypic variation. These major QTLs were co-located in two genomic regions on chromosome 5A and 6A, namely QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. By developing kompetitive allele-specific PCR (KASP) markers that linked to them, the two loci were validated in different genetic backgrounds, and their interactions were also analyzed. Comparison analysis showed that QSc/Sl.cib-5A was not Vrn-A1 and Q, and QSc/Sl.cib-6A was likely a new locus for SC and SL. Both QSc/Sl.cib-5A and QSc/Sl.cib-6A had pleiotropic effects on other yield-related traits including plant height, thousand grain weight and grain length. Therefore, the two loci combined with the developed KASP markers might be potentially applicable in wheat breeding. Furthermore, based on the spatiotemporal expression patterns, gene annotation, orthologous search and sequence differences, TraesCS5A01G301400 and TraesCS6A01G090300 were considered as potential candidates for QSc/Sl.cib-5A and QSc/Sl.cib-6A, respectively. These results provided valuable information for fine mapping and cloning of the two loci in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00122-021-03918-8DOI Listing
July 2021

Aberrant Development of Cross-Frequency Multiplex Functional Connectome in First-Episode, Drug-Naive Major Depressive Disorder and Schizophrenia.

Brain Connect 2021 Jul 16. Epub 2021 Jul 16.

South China Normal University, 12451, ZhongShan Street West NO.55, Guangzhou, Guangdong, China, 510631;

Background: Major depressive disorder (MDD) and schizophrenia (SCH) are both characterized by neurodevelopmental abnormalities; however, transdiagnostic and diagnosis-specific patterns of such abnormalities have rarely been examined, particularly in large-scale functional brain networks via advanced multilayer network models.

Methods: Here we collected resting-state functional MRI data from 45 MDD patients, 64 SCH patients and 48 healthy controls (13-45 years old), and constructed functional networks in different frequency intervals. The frequency-dependent networks were then fused by multiplex network models, followed by graph-based topological analyses.

Results: We found that functional networks of the patients showed common neurodevelopmental abnormalities in the right ventromedial parietooccipital sulcus (opposite correlations with age to healthy controls), while functional networks of the MDD patients exhibited specific alterations in the left superior parietal lobule and right precentral gyrus with respect to cross-frequency interactions. These findings were quite different from those from brain networks within each frequency interval, which revealed SCH-specific neurodevelopmental abnormalities in the right superior temporal gyrus (opposite correlations with age to the other two groups) in 0.027-0.073 Hz, and SCH-specific alterations in the left superior temporal gyrus and bilateral insula in 0.073-0.198 Hz. Finally, multivariate analysis of age prediction revealed that the subcortical network lost predict ability in both patient groups, while the visual network exhibited additional prediction ability in the MDD patients.

Discussion And Conclusion: Altogether, these findings demonstrate transdiagnostic and diagnosis-specific neurodevelopmental abnormalities and alterations in large-scale functional brain networks between MDD and SCH, which have important implications for understanding shared and unique neural mechanisms underlying the diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/brain.2021.0088DOI Listing
July 2021

High-resolution characterization of gene function using single-cell CRISPR tiling screen.

Nat Commun 2021 07 1;12(1):4063. Epub 2021 Jul 1.

Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.

Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via CRISPR tiling of gene-coding exons has been demonstrated to identify functional regions in genes. Furthermore, breakthroughs in combining CRISPR library screens with single-cell droplet RNA sequencing (sc-RNAseq) platforms have revealed the capacity to monitor gene expression changes upon genetic perturbations at single-cell resolution. Here, we present "sc-Tiling," which integrates a CRISPR gene-tiling screen with single-cell transcriptomic and protein structural analyses. Distinct from other reported single-cell CRISPR screens focused on observing gene function and gene-to-gene/enhancer-to-gene regulation, sc-Tiling enables the capacity to identify regulatory mechanisms within a gene-coding region that dictate gene activity and therapeutic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-24324-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249386PMC
July 2021

3-Benzoylisoxazolines by 1,3-Dipolar Cycloaddition: Chloramine-T-Catalyzed Condensation of α-Nitroketones with Dipolarophiles.

Molecules 2021 Jun 8;26(12). Epub 2021 Jun 8.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilisation, Ministry of Education, School of Pharmaceutical Sciences, Shihezi University, Shihezi 832002, China.

In this study, 3-benzoylisoxazolines were synthesized by reacting alkenes with various α-nitroketones using chloramine-T as the base. The scope of α-nitroketones and alkenes is extensive, including different alkenes and alkynes to form various isoxazolines and isoxazoles. The use of chloramine-T, as the low-cost, easily handled, moderate base for 1,3-dipolar cycloaddition is attractive.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26123491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227129PMC
June 2021

Actein Antagonizes Oral Squamous Cell Carcinoma Proliferation through Activating FoxO1.

Pharmacology 2021 Jun 25:1-13. Epub 2021 Jun 25.

Department of Emergency and General Dentistry, Tianjin Stomatology Hospital, NanKai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China.

Background: Oral squamous cell carcinoma (OSCC) is among the most prevalent head and neck malignancies globally, and it is associated with high mortality rates. Actein is one of the primary active components extractable from the rhizomes of Cimicifuga foetida. This study aimed to evaluate the anti-OSCC effects of actein and evaluate the potential underlying mechanisms.

Methods And Results: CCK-8 cell proliferation experiments demonstrated significant dose- and time-dependent anti-OSCC effects of actein, while actein had weak cytotoxic effects on normal oral cell lines. Flow cytometry for cell cycle evaluation revealed that actein could induce cell cycle arrest at the G1 phase among OSCC cell lines. In our Annexin V/PI double staining apoptosis analysis, actein induced significant apoptosis among OSCC cells, with upregulation of Bax and downregulation of Bcl-2. Our mechanistic study implicated the involvement of the Akt/FoxO1 pathway in the anti-OSCC effects of actein. Akt1 and Akt2 expression significantly decreased in association with the FoxO1 upregulation. Furthermore, Bim and p21 were significantly upregulated, while survivin expression was downregulated. Finally, actein treatment was associated with significant p-Akt downregulation and p-FoxO1 upregulation in OSCC cells, demonstrating the validated roles of Akt/FoxO1 in actein-mediated OSCC cell apoptosis and cell cycle arrest. FoxO1 knockdown significantly reversed the anti-OSCC effects of actein. Additionally, a xenograft model indicated that actein could inhibit OSCC cell growth in vivo.

Conclusions: Our findings demonstrated that actein could be a strong anti-OSCC candidate. Further evaluations of its safety and effectiveness are necessary before it can be considered for clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000515601DOI Listing
June 2021

, a novel causal agent of maize ear rot and its sensitivity to fungicides.

Plant Dis 2021 Jun 22. Epub 2021 Jun 22.

Plant Protection Institute, Hebei Academy of Agricultural and Forestry Sciences, Baoding, China.

Ear rot is one of the most prevalent and destructive diseases on maize. During field surveys in recent years, it was found that a Penicillium ear rot broke out in some areas of Shanxi, Shaanxi, Hebei and Tianjin in China, with an incidence of 3%-90%. A sp. was isolated from diseased kernels covered with greyish green mold, and three isolates were identified by morphological and molecular characteristics. The pathogenicity of isolate ZBS205 to maize ears was further determined by artificial inoculation in a field. Furthermore, the sensitivity of isolate ZBS205 against six commonly-used fungicides was also evaluated. According to macro- and micro-morphological characteristics, isolate ZBS205 was generally identical to (teleomorph of ). The partial gene sequences of the nuclear ribosomal ITS1-5.8S-ITS2 (ITS) region, , putative ribosome biogenesis protein () and the second largest subunit of the RNA polymerase II () from isolates ZBS205, D49-1 and S73-1 showed the highest nucleotide identity to strain X33, and the phylogenetic analysis conducted by neighbor-joining method with the combined data of the four genes demonstrated that these three isolates clustered with strain X33. These results suggested that the fungus isolated from diseased maize kernels was . Pathogenicity testing showed that the isolate ZBS205 was pathogenic to maize ears, which showed symptoms of rotted cob and deteriorated kernels. This is the first report of as the definitive pathogen causing maize ear rot. The result of fungal sensitivity against fungicides showed that pyraclostrobin exhibited the highest toxicity to mycelial growth and could be used as a candidate agent for the prevention and control of ear rot. Results of the present study provide a basis for understanding ear rot caused by , and should play an important role in disease management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1094/PDIS-04-21-0686-REDOI Listing
June 2021

HCV poly U/UC sequence-induced inflammation leads to metabolic disorders in vulvar lichen sclerosis.

Life Sci Alliance 2021 Aug 18;4(8). Epub 2021 Jun 18.

Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology and School of Life Sciences, Fudan University, Shanghai, China

Vulvar lichen sclerosis (VLS) is a dermatologic disorder that affects women worldwide. Women with VLS have white, atrophic papules on the vulva. They suffer from life-long intense pruritus. Corticosteroids are the first-line of treatments and the most effective medicines for VLS. Although VLS has been speculated as an autoimmune disease for a long time, its pathogenesis and the molecular mechanism is largely unknown. We performed a comprehensive multi-omics analysis of paired samples from VLS patients as well as healthy donors. From the RNA-seq analysis, we found that VLS is correlated to abnormal antivirus response because of the presence of Hepatitis C Virus poly U/UC sequences. Lipidomic and metabolomic analysis revealed that inflammation-induced metabolic disorders of fatty acids and glutathione were likely the reasons for pruritus, atrophy, and pigment loss in the vulva. Thus, the present study provides an initial interpretation of the pathogenesis and molecular mechanism of VLS and suggests that metabolic disorders that affect the vulva may serve as therapeutic targets for VLS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.26508/lsa.202000906DOI Listing
August 2021

Design, synthesis and biological evaluation of dual mTOR/HDAC6 inhibitors in MDA-MB-231 cells.

Bioorg Med Chem Lett 2021 Jun 14;47:128204. Epub 2021 Jun 14.

Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Baojian Road 157, Nangang District, Harbin 150081, PR China. Electronic address:

The excessive activation of histone deacetylase (HDAC) and mammalian target of rapamycin (mTOR) signaling promotes tumor growth and progression. We proposed that dual targeting mTOR and HDAC inhibitors is a promising strategy for triple negative breast cancer (TNBC) treatment. In this study, a series of dual mTOR/HDAC6 inhibitors were designed and synthesized by structure-based strategy. 10g was documented to be a potent dual mTOR/HDAC6 inhibitor with IC value of 133.7 nM against mTOR and 56 nM against HDAC6, presenting mediate antiproliferative activity in TNBC cells. Furthermore, we predicted the binding mode of 10g and mTOR/HDAC6 by molecule docking. In addition, 10g was documented to induce significant autophagy, apoptosis and suppress migration in MDA-MB-231 cells. Collectively, these findings revealed that 10g is a novel potent dual mTOR/HDAC6 inhibitor, which provides promising rationale for the combination of dual mTOR/HDAC6 inhibitors for TNBC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2021.128204DOI Listing
June 2021

Parasexual reproduction in : Simple sequence repeat molecular evidence for haploidization.

Mycologia 2021 Jun 14:1-7. Epub 2021 Jun 14.

College of Plant Protection, Hebei Agricultural University, Baoding, China.

Multiple alleles were constantly detected in isolates by simple sequence repeat (SSR) analysis, and sectors were also observed in their subcultures. These preliminary results and observations point to a possible parasexual cycle in . In this study, codominant SSR markers were used as molecular markers on the chromosomes of and single-conidium subculture was used to simulate the mitosis process of in nature. The number of alleles at locus As-95236 changed from 2 to 1 as a molecular marker for haploidy of parasexuality of . Fifty monosporic F1 strains were tested. The results showed that two parent strains lost allele with a haploid probability of 38%. For F2 strains, the results showed that all four F1 strains lost allele with a haploid probability of 75%. Since sexual recombination of has not been found so far, the allele lost in the subcultures of isolates provides molecular evidence for the existence of parasexual reproduction in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00275514.2021.1922243DOI Listing
June 2021

miR-129-5p in exosomes inhibits diabetes-associated osteogenesis in the jaw via targeting FZD4.

Biochem Biophys Res Commun 2021 Aug 10;566:87-93. Epub 2021 Jun 10.

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address:

Diabetes mellitus (DM) influence induces poor osseointegration. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is a critical factor in successful dental implants. Certain microRNAs play important roles during bone development, and others are deregulated in diabetes. This study investigated the roles of miR-129-5p in the osteoblast differentiation regulation. Exosomes containing miR-129-5p inhibited the osteoblast differentiation and was found in the blood of DM rats. The BMSCs isolated from the jaw of rats were used to detect the miR-129-5p expression. Frizzled (FZD) proteins function as receptors for WNT ligands. The FZD4 was the target of miR-129-5p in dual luciferase assay and Western blot. The miR-129-5p inhibited osteoblast differentiation and decreased the osteoblast markers. The exosomes isolated from the blood of DM rats showed more miR-129-5p level. Results suggested that the exosomes containing miR-129-5p maybe regulators of BMSCs in jaw. The collected exosomes containing miR-129-5p showed the inhibition effect in osteoblast differentiation and decreased the expression osteoblastic markers by targeting FZD4/β-catenin signaling pathway. Therefore, the exosomes containing miR-129-5p in DM rats inhibits osteoblast differentiation by targeting FZD4/β-catenin pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2021.05.072DOI Listing
August 2021

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.

Nat Commun 2021 06 11;12(1):3579. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196104PMC
June 2021

Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis.

Commun Biol 2021 06 2;4(1):660. Epub 2021 Jun 2.

Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA, USA.

The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands. The lineage-specific genes infer cells of origin of breast cancer using The Cancer Genome Atlas data and single-cell RNA sequencing of human breast cancer, as well as the association of gland reorganization to different breast cancer subtypes. This comprehensive mammary cell gene expression atlas ( https://mouse-mammary-epithelium-integrated.cells.ucsc.edu ) presents insights into the impact of the internal and external stimuli on the mammary epithelium at an advanced resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-02201-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172904PMC
June 2021

The coupling of BOLD signal variability and degree centrality underlies cognitive functions and psychiatric diseases.

Neuroimage 2021 08 19;237:118187. Epub 2021 May 19.

State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute of Brain Research, Beijing Normal University, Beijing 100875, PR China. Electronic address:

Brain signal variability has been consistently linked to functional integration; however, whether this coupling is associated with cognitive functions and/or psychiatric diseases has not been clarified. Using multiple multimodality datasets, including resting-state functional magnetic resonance imaging (rsfMRI) data from the Human Connectome Project (HCP: N = 927) and a Beijing sample (N = 416) and cerebral blood flow (CBF) and rsfMRI data from a Hangzhou sample (N = 29), we found that, compared with the existing variability measure (i.e., SD), the mean-scaled (standardized) fractional standard deviation of the BOLD signal (mfSD) maintained very high test-retest reliability, showed greater cross-site reliability and was less affected by head motion. We also found strong reproducible couplings between the mfSD and functional integration measured by the degree centrality (DC), both cross-voxel and cross-subject, which were robust to scanning and preprocessing parameters. Moreover, both mfSD and DC were correlated with CBF, suggesting a common physiological basis for both measures. Critically, the degree of coupling between mfSD and long-range DC was positively correlated with individuals' cognitive total composite scores. Brain regions with greater mismatches between mfSD and long-range DC were more vulnerable to brain diseases. Our results suggest that BOLD signal variability could serve as a meaningful index of local function that underlies functional integration in the human brain and that a strong coupling between BOLD signal variability and functional integration may serve as a hallmark of balanced brain networks that are associated with optimal brain functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118187DOI Listing
August 2021

Berberine Attenuates Cerebral Ischemia-Reperfusion Injury Induced Neuronal Apoptosis by Down-Regulating the CNPY2 Signaling Pathway.

Front Pharmacol 2021 28;12:609693. Epub 2021 Apr 28.

Department of Central Laboratory, Tianjin 4th Centre Hospital, The Fourth Central Hospital Affiliated to Nankai University, Tianjin, China.

Berberine (BBR) has a neuroprotective effect against ischemic stroke, but its specific protective mechanism has not been clearly elaborated. This study explored the effect of BBR on the canopy FGF signaling regulator 2 (CNPY2) signaling pathway in the ischemic penumbra of rats. The model of cerebral ischemia-reperfusion injury (CIRI) was established by the thread embolization method, and BBR was gastrically perfused for 48 h or 24 h before operation and 6 h after operation. The rats were randomly divided into four groups: the Sham group, BBR group, CIRI group, and CIRI + BBR group. After 2 h of ischemia, followed by 24 h of reperfusion, we confirmed the neurologic dysfunction and apoptosis induced by CIRI in rats ( < 0.05). In the ischemic penumbra, the expression levels of CNPY2-regulated endoplasmic reticulum stress-induced apoptosis proteins (CNPY2, glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), C/EBP homologous protein (CHOP), and Caspase-3) were significantly increased, but these levels were decreased after BBR treatment ( < 0.05). To further verify the inhibitory effect of BBR on CIRI-induced neuronal apoptosis, we added an endoplasmic reticulum-specific agonist and a PERK inhibitor to the treatment. BBR was shown to significantly inhibit the expression of apoptotic proteins induced by endoplasmic reticulum stress agonist, while the PERK inhibitor partially reversed the ability of BBR to inhibit apoptotic protein ( < 0.05). These results confirm that berberine may inhibit CIRI-induced neuronal apoptosis by downregulating the CNPY2 signaling pathway, thereby exerting a neuroprotective effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.609693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113774PMC
April 2021

Identification and candidate gene mining of HvSS1, a novel qualitative locus on chromosome 6H, regulating the uppermost internode elongation in barley (Hordeum vulgare L.).

Theor Appl Genet 2021 Aug 3;134(8):2481-2494. Epub 2021 May 3.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, Sichuan, People's Republic of China.

Key Message: A novel qualitative locus regulating the uppermost internode elongation of barley was identified and mapped on 6H, and the candidate gene mining was performed by employing various barley genomic resources. The stem of grass crops, such as barley and wheat, is composed of several interconnected internodes. The extent of elongation of these internodes determines stem height, and hence lodging, canopy architecture, and grain yield. The uppermost internode (UI) is the last internode to elongate. Its elongation contributes largely to stem height and facilitates spike exsertion, which is crucial for final grain yield. Despite the molecular mechanism underlying regulation of UI elongation was extensively investigated in rice, little is known in barley. In this study, we characterized a barley spontaneous mutant, Sheathed Spike 1 (SS1), showing significantly shortened UI and sheathed spike (SS). The extension of UI parenchyma cell in SS1 was significantly suppressed. Exogenous hormone treatments and RNA-seq analysis indicated that the suppression of UI elongation is possibly related to insufficient content of endogenous bioactive gibberellin. Genetic analysis showed that SS1 is possibly controlled by a qualitative dominant nuclear factor. Bulked segregant analysis and further molecular marker mapping identified a novel major locus, HvSS1, in a recombination cold spot expanding 173.44-396.33 Mb on chromosome 6H. The candidate gene mining was further conducted by analyzing sequence differences, spatiotemporal expression patterns, and variant distributions of genes in the candidate interval by employing various barley genomic resources of worldwide collections of barley accessions. This study made insight into genetic control of UI elongation in barley and laid a solid foundation for further gene cloning and functional characterization. The results obtained here also provided valuable information for similar research in wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00122-021-03837-8DOI Listing
August 2021

A four-hypoxia-genes-based prognostic signature for oral squamous cell carcinoma.

BMC Oral Health 2021 05 3;21(1):232. Epub 2021 May 3.

Department of Oral and Maxillofacial Surgery, Tianjin Stomatology Hospital, School of Medicine, NanKai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, No. 75, Dagu North Road, Heping District, Tianjin, 300041, China.

Background: Oral squamous cell carcinoma (OSCC) is one of the most common maligancies of the head and neck. The prognosis was is significantly different among OSCC patients. This study aims to identify new biomarkers to establish a prognostic model to predict the survival of OSCC patients.

Methods: The mRNA expression and corresponding clinical information of OSCC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus. Additionally, a total of 26 hypoxia-related genes were also obtained from a previous study. Univariate Cox regression analysis and LASSO Cox regression analysis were performed to screen the optimal hypoxia-related genes which were associated with the prognosis of OSCC. to establish the predictive model (Risk Score) was established for estimating the patient's overall survival (OS). Multivariate Cox regression analysis was used to determine whether the Risk Score was an independent prognostic factor. Based on all the independent prognostic factors, nomogram was established to predict the OS probability of OSCC patients. The relative proportion of 22 immune cell types in each patient was evaluated by CIBERSORT software.

Results: We determined that a total of four hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA were significantly associated with the prognosis of OSCC patients. The nomogram established based on all the independent factors could reliably predict the long-term OS of OSCC patients. In addition, our resluts indicated that the inferior prognosis of OSCC patients with high Risk Score might be related to the immunosuppressive microenvironments.

Conclusion: This study shows that high expression of hypoxia-related genes including ALDOA, P4HA1, PGK1 and VEGFA is associated with poor prognosis in OSCC patients, and they can be used as potential markers for predicting prognosis in OSCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12903-021-01587-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094530PMC
May 2021

PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol.

Gen Psychiatr 2021 5;34(2):e100440. Epub 2021 Apr 5.

Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.

Methods And Analysis: This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to 'escitalopram+golimumab (TNF-α inhibitor)', 'escitalopram+calcium tablet+vitamin D (PKC activator)' or 'escitalopram+placebo' groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.

Discussion: This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.

Trial Registration Number: The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gpsych-2020-100440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030460PMC
April 2021

Time Distributions of Common Respiratory Pathogens Under the Spread of SARS-CoV-2 Among Children in Xiamen, China.

Front Pediatr 2021 12;9:584874. Epub 2021 Apr 12.

Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children's Hospital (Children's Hospital of Fudan University Xiamen Branch), Xiamen, China.

The aim of this study was to observe the effect of COVID-19 prevention and control measures on the transmission of common respiratory viruses in a pediatric population. This was a retrospective observational study. The study population was selected from children with respiratory diseases who attended Xiamen Children's Hospital from January 1, 2018 to January 31, 2021. All children were screened for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The changes in respiratory virus detection rates before and after the SARS-CoV-2 intervention were analyzed using an interrupted time-series model. Polynomial curve fitting was also used to predict future short-term trends in respiratory virus detection. A total of 56,859 children were seen at Xiamen Children's Hospital from January 1, 2018 to Jan 31, 2021, of which 32,120 were tested for respiratory viruses via pharyngeal swabs. The overall positive detection rates of the four respiratory viral infections decreased significantly ( = 0.0017) after the implementation of the quarantine and school suspension measures in January 2020. Among them, the detection rate of RSV decreased most significantly ( = 0.008), and although there was no statistically significant difference in the detection rates of the influenza virus, parainfluenza virus, and adenovirus, a downward trend in the graph was observed. The positive detection rates of RSV in the 0-1-, 1-3-, and 3-7-year-old groups all decreased significantly ( = 0.035, 0.016, and 0.038, respectively). The change in the positive detection rate of RSV was relatively stable in the 7-18-year-old group. A total of 10,496 samples were tested for SARS-CoV-2, and no positive cases were reported. The combination of preventive and control measures for COVID-19 reduced the detection rate of four common respiratory viruses, with the greatest impact on RSV. If prevention and control measures continue to be maintained, the overall detection rate or absolute number of detections for the four respiratory viruses will remain low in the short term. However, this trend is likely to vary with the changes in measures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.584874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075055PMC
April 2021

Correction: A mitochondria-targeted dual-functional aggregation-induced emission luminogen for intracellular mitochondrial imaging and photodynamic therapy.

Biomater Sci 2021 Apr;9(8):3171

The Laboratory of Clinical Pharmacy, The People's Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China.

Correction for 'A mitochondria-targeted dual-functional aggregation-induced emission luminogen for intracellular mitochondrial imaging and photodynamic therapy' by Yujie Zhang et al., Biomater. Sci., 2021, 9, 1232-1236, DOI: 10.1039/D0BM02099K.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1bm90032cDOI Listing
April 2021

Investigation of the combined use of capping and oxidizing agents in the immobilization of arsenic in sediments.

Sci Total Environ 2021 Aug 6;782:146930. Epub 2021 Apr 6.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China.

The combined use of capping (lanthanum modified bentonite; LMB) and oxidizing (calcium nitrate; CN) agents was investigated to immobilize arsenic (As) in sediments. The vertical changes in labile As and dissolved As were measured using diffusive gradients in thin films (DGT) and Rhizon devices. The results showed that the combined application of LMB and CN had the optimal effect on the immobilization of both DGT-labile As and dissolved As, compared to single treatments using LMB or CN. After 60 days of incubation, the maximum reduction efficiencies of DGT-labile As at sediment depths were 76.4%, 70.8%, and 44.9% of those treated with LMB + CN, CN, and LMB, respectively. After 32 days of incubation, the average concentrations of dissolved total As throughout the depths decreased from 7.71 μg/L after the control treatment without any amendments to 5.25, 4.03, and 3.15 μg/L after the addition of LMB, CN, and LMB + CN, respectively. The larger part of exchangeable As at sediment depths was converted into the reducible As mainly bound Fe/Mn oxide-hydroxides after combining LMB and CN. Due to the As(III) existing mainly in the form of electrically neutral HAsO in sediments, it is hard to adsorb As(III) for the LMB and iron/manganese oxide-hydroxides formed by the oxidation effect of calcium nitrate. Thus, the single or combined LMB and CN use had much weaker effect on the immobilization of As(III) compared with As(V). The results of current study indicated that the combined use of LMB and CN could be a promising method to control the potential release of As from the sediment to the overlying water. However, this method needs further improvement to achieve a better immobilization effect on As(III) in sediments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.146930DOI Listing
August 2021

The anti-depressant effects of a novel PDE4 inhibitor derived from resveratrol.

Pharm Biol 2021 Dec;59(1):418-423

School of Pharmacy & School of Medicine, Changzhou University, Changzhou, PR China.

Context: Resveratrol has shown anti-stress and anti-depressant-like abilities involved in inhibiting phosphodiesterase-4 (PDE4) enzyme. However, its application is limited due to its low efficacy, bioavailability and selectivity.

Objective: This study synthesized a new resveratrol derivative RES003 and evaluated its PDE4 inhibitory and anti-depressant-like activities and , respectively.

Materials And Methods: PDEs inhibitory activities were evaluated by radioactive tracer method. Anti-depressant-like activities of novel resveratrol analogue (RES003) at doses of 2.5, 5.0 and 10 mg/kg was investigated by sugar water consumption and forced swimming tests using male ICR mice under chronic unpredictable stress procedure for 10 days. A total of 84 mice were randomly distributed into seven groups ( = 12). Drugs and vehicle were administered (intra-gastric or intra-peritoneal) once a day from the first to the last day. The molecular mechanisms were identified by western blot.

Results: RES003 showed more potent PDE4 inhibitory activity (half maximal inhibitory concentration (IC), 0.87 μM) and better selectivity than resveratrol (IC, 18.8 μM). RES003 could significantly increase the consumption of sugar water ( < 0.01) and immobility time ( < 0.01) compared to vehicle-treated stressed groups at doses of 5 and 10 mg/kg. Furthermore, RES003 could significantly increase the levels of cyclic adenosine monophosphate response element binding protein phosphorylation (10 mg/kg,  < 0.05) and brain-derived neurotrophic factor (BDNF) expression (5 and 10 mg/kg,  < 0.05 and 0.01) in mouse brain.

Discussion And Conclusions: RES003 could ameliorate chronic stress induced depression-like behaviours through inhibition of PDE4 and activation of cAMP-triggered phosphorylation of cAMP response element binding protein/BDNF signalling pathway. Consequently, RES003 is a promising lead compound for the treatment of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13880209.2021.1907422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049461PMC
December 2021

Surface-based single-subject morphological brain networks: Effects of morphological index, brain parcellation and similarity measure, sample size-varying stability and test-retest reliability.

Neuroimage 2021 07 29;235:118018. Epub 2021 Mar 29.

Institute for Brain Research and Rehabilitation, Guangdong Key Laboratory of Mental Health and Cognitive Science, Center for Studies of Psychological Application, South China Normal University, Guangzhou, China; Key Laboratory of Brain, Cognition and Education Sciences (South China Normal University), Ministry of Education. Electronic address:

Morphological brain networks, in particular those at the individual level, have become an important approach for studying the human brain connectome; however, relevant methodology is far from being well-established in their formation, description and reproducibility. Here, we extended our previous study by constructing and characterizing single-subject morphological similarity networks from brain volume to surface space and systematically evaluated their reproducibility with respect to effects of different choices of morphological index, brain parcellation atlas and similarity measure, sample size-varying stability and test-retest reliability. Using the Human Connectome Project dataset, we found that surface-based single-subject morphological similarity networks shared common small-world organization, high parallel efficiency, modular architecture and bilaterally distributed hubs regardless of different analytical strategies. Nevertheless, quantitative values of all interregional similarities, global network measures and nodal centralities were significantly affected by choices of morphological index, brain parcellation atlas and similarity measure. Moreover, the morphological similarity networks varied along with the number of participants and approached stability until the sample size exceeded ~70. Using an independent test-retest dataset, we found fair to good, even excellent, reliability for most interregional similarities and network measures, which were also modulated by different analytical strategies, in particular choices of morphological index. Specifically, fractal dimension and sulcal depth outperformed gyrification index and cortical thickness, higher-resolution atlases outperformed lower-resolution atlases, and Jensen-Shannon divergence-based similarity outperformed Kullback-Leibler divergence-based similarity. Altogether, our findings propose surface-based single-subject morphological similarity networks as a reliable method to characterize the human brain connectome and provide methodological recommendations and guidance for future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118018DOI Listing
July 2021

Relationship Between Serum Inflammatory Factor Levels and Differentiated Thyroid Carcinoma.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033821990055

Deparment of Surgical Oncology, Lu'an Hospital Affiliated to Anhui Medical University, Lu'an, China.

Background: Some evidence supports that the significance of inflammation is linked to a variety of tumors, including thyroid carcinoma. This work measured the preoperative serum inflammatory factors in thyroid tumors to explore their diagnostic values.

Material And Methods: Altogether 487 thyroid tumor patients were recruited, their neutrophil (NE), white blood cell (WBC), monocyte (MO), lymphocyte (LY), platelet (PLT) counts, together with monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), interleukin (IL)-1β, IL-2, IL-27, and tumor necrosis factor-α (TNF-α) levels were compared with controls. Afterward, the receiver operating characteristics (ROC) curve was plotted to further evaluate the values of these inflammatory markers in diagnosis. In addition, multivariable regression analysis was conducted to analyze all these inflammatory factors.

Results: Serum PLR, NLR, CRP, and IL-27 levels in thyroid adenoma (TA) and differentiated thyroid carcinoma (DTC) patients were higher than those in controls. Only the areas under the curve (AUC) for CRP and IL-27 were significant in the context of DTC. Besides, the AUC for IL-27 was significant between papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) groups, while that for NLR+PLR was also significant between PTC and healthy control groups. According to multivariable logistic regression analysis, IL-27 and CRP were associated with DTC.

Conclusions: Inflammation plays an important role in TA and DTC progression. Preoperative IL-27 and CRP levels help to differentially diagnose DTC. Moreover, IL-27 assists in distinguishing FTC from PTC, and NLR+PLR is important for the differential diagnosis of PTC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1533033821990055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093610PMC
March 2021

Alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC): a retrospective study of 27 cases.

Arch Gynecol Obstet 2021 Mar 9. Epub 2021 Mar 9.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

Objective: The aim of the study was to investigate the relative risk factors associated with the prognosis and effective treatments of alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC).

Method: We presented three cases of AFP-producing EOC and performed a brief review to summarize the clinicopathological features and prognostic factors of 24 cases that have been previously reported. We evaluated the correlations among prognostic and clinical parameters, such as stage, pathology and chemotherapy regimens. In addition, a retrospective review of these 27 cases was conducted, and survival curves were estimated using the Kaplan-Meier method.

Results: The patients were aged between 23 and 77 years. The median overall survival was 10 months, and ten (37.04%) patients died within 18 months. We compared the overall mean survival times of all patients in different stages, and the results suggest that the postoperative pathological staging is hardly correlated with prognosis (P = 0.76). There was a correlation between pathology and prognosis (P = 0.0018). The mean survival time was longer for patients who had undergone chemotherapy than for those without chemotherapy (14.88 vs 0.65 months) (P < 0.0001). Moreover, although patients had a good response to the regimens for PEB and TC (P = 0.004), there was no significant difference between PEB and TC (P = 0.386).

Conclusions: AFP-producing EOC is uncommon and regarded as an extremely malignant type of tumor. Patients with chemotherapy may have a longer survival time; additionally, PEB and TC may be an optimal selection for this kind of tumor. Further large-scale studies are needed to confirm our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-021-06017-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942666PMC
March 2021

L. Attenuates Cigarette Smoke and Lipopolysaccharide-Induced COPD in Rats via Inflammation Inhibition and Antioxidant and Antifibrosis Pathways.

Evid Based Complement Alternat Med 2021 2;2021:6103158. Epub 2021 Mar 2.

Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, College of Pharmacy, Shihezi University, Shihezi 832002, China.

The root cause behind the development of chronic obstructive pulmonary disease (COPD) is cigarette smoke that induces the inflammation of the lung tissue and alveolar destruction. Long-term cigarette smoking can lead to deterioration in lung parenchymal function and cause structural changes in the lung, further resulting in pulmonary fibrosis. L., a traditional medicinal perennial herb, is well known for its numerous pharmacological benefits, including anti-inflammation, antioxidant, antifatigue, antidepressive, and antifibrotic properties. Here, we evaluated the pharmacological effects and mechanisms of the L. (RRL) macroporous resin extract on COPD caused by lipopolysaccharide (LPS) and cigarette smoke (CS) in rats. The RRL significantly improved the pathological structure of the lung tissue. Additionally, RRL decreased the infiltration of inflammatory cells and, subsequently, oxidative stress. Furthermore, the RNAseq assay indicated that RRL attenuated the CS and LPS-induced COPD via anti-inflammatory, antifibrotic, and antiapoptotic activities. Western blot analysis substantiated that the RRL resulted in upregulated levels of Nrf2 and HO-1 as well as downregulated levels of IB, NF-B p65, -SMA, and TGF-1. Interestingly, the RRL could protect rats from CS and LPS-induced COPD by inhibiting the ERK1/2 and Smad3 signaling pathways and apoptosis. Thus, the RRL could attenuate CS and LPS-induced COPD through inflammation inhibition and antioxidant and antifibrosis pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6103158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943302PMC
March 2021

Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes and in an Cocktail Method.

Front Pharmacol 2020 5;11:593518. Epub 2021 Jan 5.

The Laboratory of Clinical Pharmacy, The Sixth Affiliated Hospital of Wenzhou Medical University, The People's Hospital of Lishui, Lishui, China.

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). As poziotinib is partially metabolized by CYPs, cocktail probes are used to study the interaction between drugs metabolized by each CYP subtype. Midazolam, bupropion, dextromethorphan, tolbutamide, chlorzoxazone, phenacetin, and their metabolites were used to examine the effects of poziotinib on the activity of cyp1a2, 2b1, 2d1, 2c11, 2e1, and 3a1/2, respectively. The experiment was carried out by using rat liver microsomes (RLMs), whereas the experiment involved the comparison of the pharmacokinetic parameters of the probes after co-administration with poziotinib to rats to those of control rats treated with only probes. UPLC-MS/MS was used to detect the probes and their metabolites in rat plasma and rat liver microsomes. The results revealed that the half-maximal inhibitory concentration values of bupropion and tolbutamide in RLMs were 8.79 and 20.17 μM, respectively, indicating that poziotinib showed varying degrees of inhibition toward cyp2b1 and cyp2c11. Poziotinib was a competitive inhibitor of cyp2b1 and cyp2c11, with Ki values of 16.18 and 17.66 μM, respectively. No time- or concentration-dependence of inhibition by poziotinib was observed toward cyp2b1 and cyp2c11 in RLMs. Additionally, no obvious inhibitory effects were observed on the activity of cyp1a2, cyp2d1, cyp2e1, and cyp3a1/2. analysis revealed that bupropion, tolbutamide, phenacetin, and chlorzoxazone showed significantly different pharmacokinetic parameters after administration ( < 0.05); there was no significant difference in the pharmacokinetic parameters of dextromethorphan and midazolam. These results show that poziotinib inhibited cyp2b1 and cyp2c11, but induced cyp1a2 and cyp2e1 in rats. Thus, poziotinib inhibited cyp2b1 and cyp2c11 activity in rats, suggesting the possibility of interactions between poziotinib and these CYP substrates and the need for caution when combining them in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2020.593518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970697PMC
January 2021

3-Phosphoglycerate dehydrogenase: a potential target for cancer treatment.

Cell Oncol (Dordr) 2021 Jun 18;44(3):541-556. Epub 2021 Mar 18.

Wuya College of Innovation, School of Pharmacy, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, China.

Background: Metabolic changes have been recognized as an important hallmark of cancer cells. Cancer cells can promote their own growth and proliferation through metabolic reprogramming. Particularly, serine metabolism has frequently been reported to be dysregulated in tumor cells. 3-Phosphoglycerate dehydrogenase (PHGDH) catalyzes the first step in the serine biosynthesis pathway and acts as a rate-limiting enzyme involved in metabolic reprogramming. PHGDH upregulation has been observed in many tumor types, and inhibition of PHGDH expression has been reported to inhibit the proliferation of PHGDH-overexpressing tumor cells, indicating that it may be utilized as a target for cancer treatment. Recently identified inhibitors targeting PHGDH have already shown effectiveness. A further in-depth analysis and concomitant development of PHGDH inhibitors will be of great value for the treatment of cancer.

Conclusions: In this review we describe in detail the role of PHGDH in various cancers and inhibitors that have recently been identified to highlight progression in cancer treatment. We also discuss the development of new drugs and treatment modalities based on PHGDH targets. Overexpression of PHGDH has been observed in melanoma, breast cancer, nasopharyngeal carcinoma, parathyroid adenoma, glioma, cervical cancer and others. PHGDH may serve as a molecular biomarker for the diagnosis, prognosis and treatment of these cancers. The design and development of novel PHGDH inhibitors may have broad implications for cancer treatment. Therapeutic strategies of PHGDH inhibitors in combination with traditional chemotherapeutic drugs may provide new perspectives for precision medicine and effective personalized treatment for cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13402-021-00599-9DOI Listing
June 2021

Identification and Validation of a Novel Locus Controlling Spikelet Number in Bread Wheat ( L.).

Front Plant Sci 2021 26;12:611106. Epub 2021 Feb 26.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

Spikelet number is an important target trait for wheat yield improvement. Thus, the identification and verification of novel quantitative trait locus (QTL)/genes controlling spikelet number are essential for dissecting the underlying molecular mechanisms and hence for improving grain yield. In the present study, we constructed a high-density genetic map for the Kechengmai1/Chuanmai42 doubled haploid (DH) population using 13,068 single-nucleotide polymorphism (SNP) markers from the Wheat 55K SNP array. A comparison between the genetic and physical maps indicated high consistence of the marker orders. Based on this genetic map, a total of 27 QTLs associated with total spikelet number per spike (TSN) and fertile spikelet number per spike (FSN) were detected on chromosomes 1B, 1D, 2B, 2D, 3D, 4A, 4D, 5A, 5B, 5D, 6A, 6B, and 7D in five environments. Among them, five QTLs on chromosome 2D, 3D, 5A, and 7D were detected in multiple environments and combined QTL analysis, explaining the phenotypic variance ranging from 3.64% to 23.28%. Particularly, for TSN and FSN [phenotypic variation explained (PVE) = 5.97-23.28%, limit of detection (LOD) = 3.73-18.51] is probably a novel locus and located in a 4.5-cM interval on chromosome arm 3DL flanking by the markers and This QTL was further validated in other two populations with different genetic backgrounds using the closely linked Kompetitive Allele-Specific PCR (KASP) marker . The results indicated that significantly increased the TSN (5.56-7.96%) and FSN (5.13-9.35%), which were significantly correlated with grain number per spike (GNS). We also preliminary analyzed the candidate genes within this locus by sequence similarity, spatial expression patterns, and collinearity analysis. These results provide solid foundation for future fine mapping and cloning of . The developed and validated KASP markers could be utilized in molecular breeding aiming to increase the grain yield in wheat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.611106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952655PMC
February 2021
-->