Transcriptome sequencing and metabolite profiling analyses provide comprehensive insight into molecular mechanisms of flower development in Dendrobium officinale (Orchidaceae)

Selective killing of cancer cells while sparing healthy ones is the principle of the perfect cancer treatment and the primary aim of many oncologists, molecular biologists, and medicinal chemists. To achieve this goal, it is crucial to understand the molecular mechanisms that distinguish cancer cells from healthy ones. Accordingly, several clinical candidates that use particular mutations in cell-cycle progressions have been developed to kill cancer cells. As the majority of cancer cells have defects in G1 control, targeting the subsequent intra‑S or G2/M checkpoints has also been extensively pursued. This review focuses on clinical candidates that target the kinases involved in intra‑S and G2/M checkpoints, namely, ATR, CHK1, and WEE1 inhibitors. It provides insight into their current status and future perspectives for anticancer treatment. Overall, even though CHK1 inhibitors are still far from clinical establishment, promising accomplishments with ATR and WEE1 inhibitors in phase II trials present a positive outlook for patient survival.

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Molecular Pathways Involved in the Development of Congenital Erythrocytosis

Genes ◽

10.3390/genes12081150 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1150

Author(s):

Jana Tomc ◽

Nataša Debeljak

Keyword(s):

Signal Transduction ◽

Iron Homeostasis ◽

Molecular Mechanisms ◽

Oxygen Affinity ◽

Molecular Pathways ◽

Disease Development ◽

Post Translational Modifications ◽

Hemoglobin Oxygen Affinity ◽

Insight Into ◽

Idiopathic Erythrocytosis

Patients with idiopathic erythrocytosis are directed to targeted genetic testing including nine genes involved in oxygen sensing pathway in kidneys, erythropoietin signal transduction in pre-erythrocytes and hemoglobin-oxygen affinity regulation in mature erythrocytes. However, in more than 60% of cases the genetic cause remains undiagnosed, suggesting that other genes and mechanisms must be involved in the disease development. This review aims to explore additional molecular mechanisms in recognized erythrocytosis pathways and propose new pathways associated with this rare hematological disorder. For this purpose, a comprehensive review of the literature was performed and different in silico tools were used. We identified genes involved in several mechanisms and molecular pathways, including mRNA transcriptional regulation, post-translational modifications, membrane transport, regulation of signal transduction, glucose metabolism and iron homeostasis, which have the potential to influence the main erythrocytosis-associated pathways. We provide valuable theoretical information for deeper insight into possible mechanisms of disease development. This information can be also helpful to improve the current diagnostic solutions for patients with idiopathic erythrocytosis.

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Pathomechanisms in the Kidneys in Selected Protozoan Parasitic Infections

International Journal of Molecular Sciences ◽

10.3390/ijms22084209 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4209

Author(s):

Karolina Kot ◽

Natalia Łanocha-Arendarczyk ◽

Michał Ptak ◽

Aleksandra Łanocha ◽

Elżbieta Kalisińska ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Molecular Mechanisms ◽

Kidney Injury ◽

Therapeutic Interventions ◽

Parasitic Infections ◽

Injury Mechanisms ◽

Kidney Involvement ◽

Leishmania Spp ◽

Apoptosis Process ◽

Insight Into

Leishmaniasis, malaria, toxoplasmosis, and acanthamoebiasis are protozoan parasitic infections. They remain important contributors to the development of kidney disease, which is associated with increased patients’ morbidity and mortality. Kidney injury mechanisms are not fully understood in protozoan parasitic diseases, bringing major difficulties to specific therapeutic interventions. The aim of this review is to present the biochemical and molecular mechanisms in kidneys infected with Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Acanthamoeba spp. We present available mechanisms of an immune response, oxidative stress, apoptosis process, hypoxia, biomarkers of renal injury in the serum or urine, and the histopathological changes of kidneys infected with the selected parasites. Pathomechanisms of Leishmania spp. and Plasmodium spp. infections have been deeply investigated, while Toxoplasma gondii and Acanthamoeba spp. infections in the kidneys are not well known yet. Deeper knowledge of kidney involvement in leishmaniasis and malaria by presenting their mechanisms provides insight into how to create novel and effective treatments. Additionally, the presented work shows gaps in the pathophysiology of renal toxoplasmosis and acanthamoebiasis, which need further research.

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The apple C2H2-type zinc finger transcription factor MdZAT10 positively regulates JA-induced leaf senescence by interacting with MdBT2

Horticulture Research ◽

10.1038/s41438-021-00593-0 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Kuo Yang ◽

Jian-Ping An ◽

Chong-Yang Li ◽

Xue-Na Shen ◽

Ya-Jing Liu ◽

...

Keyword(s):

Mass Spectrometry ◽

Transcription Factor ◽

Liquid Chromatography ◽

Zinc Finger ◽

Leaf Senescence ◽

Transcriptional Activity ◽

Molecular Mechanisms ◽

Liquid Chromatography Mass Spectrometry ◽

Zinc Finger Transcription Factor ◽

Insight Into

AbstractJasmonic acid (JA) plays an important role in regulating leaf senescence. However, the molecular mechanisms of leaf senescence in apple (Malus domestica) remain elusive. In this study, we found that MdZAT10, a C2H2-type zinc finger transcription factor (TF) in apple, markedly accelerates leaf senescence and increases the expression of senescence-related genes. To explore how MdZAT10 promotes leaf senescence, we carried out liquid chromatography/mass spectrometry screening. We found that MdABI5 physically interacts with MdZAT10. MdABI5, an important positive regulator of leaf senescence, significantly accelerated leaf senescence in apple. MdZAT10 was found to enhance the transcriptional activity of MdABI5 for MdNYC1 and MdNYE1, thus accelerating leaf senescence. In addition, we found that MdZAT10 expression was induced by methyl jasmonate (MeJA), which accelerated JA-induced leaf senescence. We also found that the JA-responsive protein MdBT2 directly interacts with MdZAT10 and reduces its protein stability through ubiquitination and degradation, thereby delaying MdZAT10-mediated leaf senescence. Taken together, our results provide new insight into the mechanisms by which MdZAT10 positively regulates JA-induced leaf senescence in apple.

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Cold-Active β-Galactosidases: Insight into Cold Adaption Mechanisms and Biotechnological Exploitation

Marine Drugs ◽

10.3390/md19010043 ◽

2021 ◽

Vol 19 (1) ◽

pp. 43

Author(s):

Marco Mangiagalli ◽

Marina Lotti

Keyword(s):

Low Temperature ◽

Molecular Mechanisms ◽

Building Blocks ◽

Cold Active ◽

Cold Adaption ◽

Glycosyl Donor ◽

Pharmaceutical Industries ◽

Biotechnological Processes ◽

Hydrolysis Of ◽

Insight Into

β-galactosidases (EC 3.2.1.23) catalyze the hydrolysis of β-galactosidic bonds in oligosaccharides and, under certain conditions, transfer a sugar moiety from a glycosyl donor to an acceptor. Cold-active β-galactosidases are identified in microorganisms endemic to permanently low-temperature environments. While mesophilic β-galactosidases are broadly studied and employed for biotechnological purposes, the cold-active enzymes are still scarcely explored, although they may prove very useful in biotechnological processes at low temperature. This review covers several issues related to cold-active β-galactosidases, including their classification, structure and molecular mechanisms of cold adaptation. Moreover, their applications are discussed, focusing on the production of lactose-free dairy products as well as on the valorization of cheese whey and the synthesis of glycosyl building blocks for the food, cosmetic and pharmaceutical industries.

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Genome-Wide Identification and Analysis of the APETALA2 (AP2) Transcription Factor in Dendrobium officinale

International Journal of Molecular Sciences ◽

10.3390/ijms22105221 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5221

Author(s):

Danqi Zeng ◽

Jaime A. Teixeira da Silva ◽

Mingze Zhang ◽

Zhenming Yu ◽

Can Si ◽

...

Keyword(s):

Transcriptional Activation ◽

Flower Development ◽

Regulatory Elements ◽

Negative Control ◽

Dendrobium Officinale ◽

Luciferase Reporter ◽

Pcr Analysis ◽

Luciferase Reporter Gene ◽

Genome Wide ◽

Ap2 Transcription Factor

The APETALA2 (AP2) transcription factors (TFs) play crucial roles in regulating development in plants. However, a comprehensive analysis of the AP2 family members in a valuable Chinese herbal orchid, Dendrobium officinale, or in other orchids, is limited. In this study, the 14 DoAP2 TFs that were identified from the D. officinale genome and named DoAP2-1 to DoAP2-14 were divided into three clades: euAP2, euANT, and basalANT. The promoters of all DoAP2 genes contained cis-regulatory elements related to plant development and also responsive to plant hormones and stress. qRT-PCR analysis showed the abundant expression of DoAP2-2, DoAP2-5, DoAP2-7, DoAP2-8 and DoAP2-12 genes in protocorm-like bodies (PLBs), while DoAP2-3, DoAP2-4, DoAP2-6, DoAP2-9, DoAP2-10 and DoAP2-11 expression was strong in plantlets. In addition, the expression of some DoAP2 genes was down-regulated during flower development. These results suggest that DoAP2 genes may play roles in plant regeneration and flower development in D. officinale. Four DoAP2 genes (DoAP2-1 from euAP2, DoAP2-2 from euANT, and DoAP2-6 and DoAP2-11 from basal ANT) were selected for further analyses. The transcriptional activation of DoAP2-1, DoAP2-2, DoAP2-6 and DoAP2-11 proteins, which were localized in the nucleus of Arabidopsis thaliana mesophyll protoplasts, was further analyzed by a dual-luciferase reporter gene system in Nicotiana benthamiana leaves. Our data showed that pBD-DoAP2-1, pBD-DoAP2-2, pBD-DoAP2-6 and pBD-DoAP2-11 significantly repressed the expression of the LUC reporter compared with the negative control (pBD), suggesting that these DoAP2 proteins may act as transcriptional repressors in the nucleus of plant cells. Our findings on AP2 genes in D. officinale shed light on the function of AP2 genes in this orchid and other plant species.

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The Dynamics of Flower Development in Castanea Sativa Mill.

Plants ◽

10.3390/plants10081538 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1538

Author(s):

Ana Teresa Alhinho ◽

Miguel Jesus Nunes Ramos ◽

Sofia Alves ◽

Margarida Rocheta ◽

Leonor Morais-Cecílio ◽

...

Keyword(s):

Flower Development ◽

Molecular Mechanisms ◽

Castanea Sativa ◽

Male And Female ◽

Sweet Chestnut ◽

Chestnut Tree ◽

Abcde Model ◽

Organ Identity ◽

Castanea Sativa Mill ◽

Female Flowers

The sweet chestnut tree (Castanea sativa Mill.) is one of the most significant Mediterranean tree species, being an important natural resource for the wood and fruit industries. It is a monoecious species, presenting unisexual male catkins and bisexual catkins, with the latter having distinct male and female flowers. Despite the importance of the sweet chestnut tree, little is known regarding the molecular mechanisms involved in the determination of sexual organ identity. Thus, the study of how the different flowers of C. sativa develop is fundamental to understand the reproductive success of this species and the impact of flower phenology on its productivity. In this study, a C. sativa de novo transcriptome was assembled and the homologous genes to those of the ABCDE model for floral organ identity were identified. Expression analysis showed that the C. sativa B- and C-class genes are differentially expressed in the male flowers and female flowers. Yeast two-hybrid analysis also suggested that changes in the canonical ABCDE protein–protein interactions may underlie the mechanisms necessary to the development of separate male and female flowers, as reported for the monoecious Fagaceae Quercus suber. The results here depicted constitute a step towards the understanding of the molecular mechanisms involved in unisexual flower development in C. sativa, also suggesting that the ABCDE model for flower organ identity may be molecularly conserved in the predominantly monoecious Fagaceae family.

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Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs

International Journal of Molecular Sciences ◽

10.3390/ijms22126644 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6644

Author(s):

Xupeng Zang ◽

Ting Gu ◽

Wenjing Wang ◽

Chen Zhou ◽

Yue Ding ◽

...

Keyword(s):

Immune Response ◽

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Gene Set ◽

Cerna Network ◽

Major Interest ◽

End Stage ◽

Insight Into

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.

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