Transduction Pathways Research Articles

Transcriptome sequencing analysis of overexpressed SikCDPK1 in tobacco reveals mechanisms of cold stress response

BackgroundCold is a significant limiting factor in productivity, particularly in northwestern and eastern China. Calcium-Dependent Protein Kinases (CDPKs), a primary calcium signaling sensor in plants, play an important role in their response to cold. Snow lotus (Sasussured involucrata Kar L) is a plant that thrives in harsh climates and grows in northwest China. However, there were no reports on the transcriptome of OE-SikCDPK1 transgenic tobacco in response to cold.ResultsWhen exposed to cold stress, OE-SikCDPK1 plants displayed a cold-tolerant phenotype compared to non-transgenic tobacco. Under cold conditions, relative water content reduced, relative conductivity increased, malondialdehyde levels rose, and cold-responsive gene expression increased. The OE-SikCDPK1 gene and non-transgenic tobacco were employed for research purposes. The transcriptome of leaves was sequenced using the HISAT2 sequencing platform, and the data were used to examine gene function annotation and differentially expressed genes (DEGs). 53,022 DEGs in tobacco leaves under cold treatment were obtained. The GO enrichment results revealed that it was enriched for biological-process, defense response and other processes under cold stress. The KEGG pathway enrichment analysis revealed that the metabolic pathways of significant enrichment of DEGs under cold stress mainly involved MAPK signaling pathway transduction. The transcription factor identification results showed that the transcription factors with the largest number of differential expressions under cold treatment were mainly from WRKY, AP2, MYB, bHLH, NAC and other transcription factor families.ConclusionThe cold tolerance mechanism of snow lotus SikCDPK1 was comprehensively analyzed at the transcriptional level for the first time using RNA-seq technology. This study demonstrates that SikCDPK1 can respond to cold by participating in the MAPK signaling pathway and regulating the expression levels of transcription factors, including WRKY, AP2, MYB, bHLH, and NAC. These results offer valuable insights for further exploration of the cold tolerance mechanism associated with SikCDPK1.

Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3β/Wnt3a-β-Catenin Pathway.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid plaques and neurofibrillary tangles. We explored the potential mechanism by which Danggui Shaoyao San (DSS) modulates central glucose metabolism via the insulin receptor substrate 1 (IRS1)/glycogen synthase kinase-3β (GSK3β)/Wnt3a-β-catenin pathway, thereby exerting protective effects on cognitive functions. In vitro, HT22 cells were induced with streptozotocin (STZ) to investigate the impact of GSK3β on pathway transduction. The active components in the DSS stock solution were validated using mass spectrometry. Subsequently, an AD model in C57BL/6J mice was established through STZ injection into both ventricles. The success of the model was validated behaviorally and pathologically. The Morris Water Maze (MWM) test, immunohistochemistry, Western blotting, quantitative reverse transcription-PCR, and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) were employed to evaluate the influence of DSS on memory and pathological changes in AD. The DSS stock solution, rich in active components, ameliorated the memory deficits in AD mice in the MWM. In vitro, GSK3β exhibited regulatory control over Wnt and β-catenin, with GSK3β inhibition mitigating β-amyloid and tau redundancies at protein and gene levels, facilitating signal transduction. In vivo, DSS impacted key targets in the IRS1/GSK3β/Wnt3a-β-catenin pathway, mitigated senile plaques resulting from amyloid β (Aβ) deposition and neurofiber tangles induced by tau hyperphosphorylation, and alleviated the decline in central glucose metabolism observed in FDG-PET. Our findings suggest that DSS potentially confers cognitive protection by alleviating central hypoglycemia through the IRS1/GSK3β/Wnt3a-β-catenin pathway. This may serve as a promising therapeutic avenue for AD.

A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity

Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood. In estrogen receptor (ER)-positive breast cancer (BC), androgen receptor (AR) is a druggable tumor suppressor offering a promising avenue for this investigation. Spatial genomics suggests that the molecular portrait of AR-expressing BC cells in tumor microenvironment corresponds to better overall patient survival, clinically confirming AR's role as a tumor suppressor. Ligand activation of AR in ER-positive BC xenografts reprograms cistromes, inhibits oncogenic pathways, and promotes cellular elasticity toward a more differentiated state. Sustained AR activation results in cistrome rearrangement toward transcription factor PROP paired-like homeobox 1, transformation of AR into oncogene, and activation of the Janus kinase/signal transducer (JAK/STAT) pathway, all culminating in lineage plasticity to an aggressive resistant subtype. While the molecular profile of AR agonist-sensitive tumors corresponds to better patient survival, the profile represented in the resistant phenotype corresponds to shorter survival. Inhibition of activated oncogenes in resistant tumors reduces growth and resensitizes them to AR agonists. These findings indicate that persistent activation of a context-dependent tumor suppressor may lead to resistance through lineage plasticity-driven tumor metamorphosis. Our work provides a framework to explore the above phenomenon across multiple cancer types and underscores the importance of factoring sensitization of tumor suppressor targets while developing agonist-like drugs.

Targeted Protein Localization by Covalent 14-3-3 Recruitment.

14-3-3 proteins have a unique ability to bind and sequester a multitude of diverse phosphorylated signaling proteins and transcription factors. Many previous studies have shown that interactions of 14-3-3 with specific phosphorylated substrate proteins can be enhanced through small-molecule natural products or fully synthetic molecular glue interactions. However, enhancing 14-3-3 interactions with both therapeutically intractable transcription factor substrates and potential neo-substrates to sequester and inhibit their function remains elusive. One of the 14-3-3 proteins, 14-3-3σ or SFN, has cysteine C38 at the substrate-binding interface, near the sites where previous 14-3-3 molecular glues have been found to bind. In this study, we screen a fully synthetic cysteine-reactive covalent ligand library to identify molecular glues that enhance the interaction of 14-3-3σ with not only druggable transcription factors such as estrogen receptor (ERα) but also challenging oncogenic transcription factors such as YAP and TAZ, which are part of the Hippo transducer pathway. We identify a hit EN171 that covalently targets both C38 and C96 on 14-3-3 to enhance 14-3-3 interactions with ERα, YAP, and TAZ, leading to impaired estrogen receptor and Hippo pathway transcriptional activity. We further demonstrate that EN171 could not only be used as a molecular glue to enhance native protein interactions but could also be used as a covalent 14-3-3 recruiter in heterobifunctional molecules to sequester nuclear neo-substrates such as BRD4 and BLC6 into the cytosol. Overall, our study reveals a covalent ligand that acts as a novel 14-3-3 molecular glue for challenging transcription factors such as YAP and TAZ and demonstrates that these glues can be potentially utilized in heterobifunctional molecules to sequester nuclear neo-substrates out of the nucleus and into the cytosol to enable targeted protein localization.

Mechanotransduction alterations in tissue-engineered tumor models for new drug interventions

Mechanotransduction is a collection of pathways in which the cells reprogram themselves by sensing mechanical stimuli. Cells use biological cues to interpret the physiological stresses and respond to changing conditions by modifying the cellular and ECM architecture. This feedback loop regulates a variety of cellular processes, including migration, growth, differentiation, and death, which is essential for the network stability to work together in a coordinated manner. The effect of stress on cancer progression and the role of mechanics as a critical inducer in determining the cancer cell fate has been studied. This review discusses the progression of cancer cells to epithelial to mesenchymal transitions. It examines tumor microenvironment models, such as spheroids, bio-printing, and microfluidics, and how they recapitulate the tumor microenvironment. These offer certain benefits and help replicate the fundamental behavior in vivo conditions. We further discuss mechanosensing, the associated signaling molecules, and how it modulates the cancer drug resistance and transduction pathways that implicate cancer treatment. The difficulties with the existing methods and the prospects for additional study that may be applied in this area are discussed, and how they allow for new therapeutic development.

Discovery of an Exceptionally Orally Bioavailable and Potent HPK1 PROTAC with Enhancement of Antitumor Efficacy of Anti-PD-L1 Therapy.

HPK1, a well-known negative regulator of T cell receptors, can cause T cell dysfunction when abnormally activated. In this study, a PROTAC C3 was designed and synthesized by optimizing the physicochemical properties of the warhead, linker, and CRBN ligand. C3 demonstrated significant HPK1 degradation with a DC50 of 21.26 nM, excellent oral absorption with a Cmax of 10,899.92 ng/mL, and a bioavailability (F %) of 81.7%. C3 also showed degradation selectivity and potent immune activation effects. Proteomic and WB analyses revealed that immune-activating effect of C3 is attributed to the inhibition of SLP76 and NF-κB signaling pathways, as well as the enhancement of MAPK signaling pathway transduction. In vivo efficacy study demonstrated that oral administration of C3 in combination with anti-PDL1 antibody significantly inhibited tumor growth (tumor growth inhibition = 65.58%). These findings suggest that C3, a novel HPK1 PROTAC, holds promise as a therapeutic agent for tumor immunotherapy.

Jiawei Taohe Chengqi Decoction attenuates CCl4 induced hepatic fibrosis by inhibiting HSCs activation via TGF-β1/CUGBP1 and IFN-γ/Smad7 pathway

BackgroundHepatic fibrosis (HF) is an essential stage in the progression of different chronic liver conditions to cirrhosis and even hepatocellular carcinoma. The activation of hepatic stellate cells (HSCs) plays a crucial role in the progression of HF. IFN- γ/Smad7 pathway can inhibit HSCs activation, while TGF-β1/CUGBP1 pathway can inhibit IFN-γ/Smad7 pathway transduction and promote HSCs activation. Thus, inhibiting the TGF-β1/CUGBP1 pathway and activating the IFN-γ/Smad7 pathway reverses HSCs activation and inhibits HF. Jiawei Taohe Chengqi Decoction (JTCD) was derived from the Taohe Chengqi Tang in the ancient Chinese medical text titled “Treatise on Febrile Diseases”. We found several anti-HF components in JTCD including ginsenoside Rb1 and others, but the specific mechanism of anti-HF in JTCD is not clear. PurposeTo elucidate the specific mechanism by which JTCD reverses HF by inhibiting the activation of HSCs, and to establish a scientific foundation for treating HF with Traditional Chinese medicine (TCM). MethodsWe constructed a CCl4-induced mice HF model in vivo and activated human hepatic stellate cell line (LX-2) with TGF-β1 in vitro, after which they were treated with JTCD and the corresponding inhibitors. We examined the expression of pivotal molecules in the two pathways mentioned above by immunofluorescence staining, Western blotting and RT-PCR. ResultsJTCD attenuated liver injury and reduced serum ALT and AST levels in mice. In addition, JTCD attenuated CCl4-induced HF by decreasing the expression of α-SMA, COL1A1 and other markers of HSCs activation in mice liver tissue. Moreover, JTCD effectively suppressed the levels of TGF-β1, p-Smad3, p-p38MAPK, p-ATF2, and CUGBP1 in vivo and in vitro and upregulated the levels of IFN-γ, p-STAT1, and Smad7. Mechanically, after using the inhibitors of both pathways in vitro, we found that JTCD inhibited the activation of HSCs by restoring the balance of the TGF-β1/CUGBP1 and IFN-γ/Smad7 pathways. ConclusionWe demonstrated that JTCD inhibited HSCs activation and reversed HF by inhibiting the TGF-β1/CUGBP1 signalling pathway and upregulating the IFN-γ/Smad7 signalling pathway. Moreover, we have identified specific links where JTCD interferes with both pathways to inhibit HSCs activation. JTCD is an effective candidate for the clinical treatment of HF.

Aquaporin Modulation by Cations, a Review.

Aquaporins (AQPs) are transmembrane channels initially discovered for their role in water flux facilitation through biological membranes. Over the years, a much more complex and subtle picture of these channels appeared, highlighting many other solutes accommodated by AQPs and a dense regulatory network finely tuning cell membranes' water permeability. At the intersection between several transduction pathways (e.g., cell volume regulation, calcium signaling, potassium cycling, etc.), this wide and ancient protein family is considered an important therapeutic target for cancer treatment and many other pathophysiologies. However, a precise and isoform-specific modulation of these channels function is still challenging. Among the modulators of AQPs functions, cations have been shown to play a significant contribution, starting with mercury being historically associated with the inhibition of AQPs since their discovery. While the comprehension of AQPs modulation by cations has improved, a unifying molecular mechanism integrating all current knowledge is still lacking. In an effort to extract general trends, we reviewed all known modulations of AQPs by cations to capture a first glimpse of this regulatory network. We paid particular attention to the associated molecular mechanisms and pinpointed the residues involved in cation binding and in conformational changes tied up to the modulation of the channel function.

GmHXK2 promotes the salt tolerance of soybean seedlings by mediating AsA synthesis, and auxin synthesis and distribution

BackgroundSalt is an important factor that affects crop productivity. Plant hexokinases (HXKs) are key enzymes in the glycolytic pathway and sugar signaling transduction pathways of plants. In previous studies, we identified and confirmed the roles of GmHXK2 in salt tolerance.ResultsIn this study, we analyzed the tissue-specific expression of GmHXK2 at different growth stages throughout the plant’s life cycle. The results showed that GmHXK2 was expressed significantly in all tissues at vegetative stages, including germination and seedling. However, no expression was detected in the pods, and there was little expression in flowers during the later mature period. Arabidopsis plants overexpressing the GmHXK2 (OE) had more lateral roots. The OE seedlings also produced higher levels of auxin and ascorbic acid (AsA). Additionally, the expression levels of genes PMM, YUC4/YUC6/YUC8, and PIN/LAX1,LAX3, which are involved respectively in the synthesis of AsA and auxin, as well as polar auxin transport, were upregulated in OE plants. This upregulation occurred specifically under exogenous glucose treatment. AtHKT1, AtSOS1, and AtNHX1 were up-regulated in OE plants under salt stress, suggesting that GmHXK2 may modulate salt tolerance by maintaining ion balance within the cells and alleviating damage caused by salt stress. Additionally, we further confirmed the interaction between GmHXK2 and the protein GmPMM through yeast two-hybridization and bimolecular fluorescence complementation assays, respectively.ConclusionThe expression of GmHXK2 gene in plants is organ-specific and developmental stage specific. GmHXK2 not only regulates the synthesis of AsA and the synthesis and distribution of auxin, but also promotes root elongation and induces lateral root formation, potentially enhancing soil water absorption. This study reveals the crosstalk between sugar signaling and hormone signaling in plants, where GmHXK2 acts as a glucose sensor through its interaction with GmPMM, and sheds light on the molecular mechanism by which GmHXK2 gene is involved in salt tolerance in plants.

Early changes in asporin levels in osteoarthritis of the temporomandibular joint

ObjectivesThe present study aimed to elucidate the pathogenesis of temporomandibular joint (TMJ) osteoarthritis (TMJ-OA) in a mouse model. We investigated morphological and histological changes in the head of mandible cartilage and early immunohistochemical (IHC) changes in transforming growth factor (TGF)-β, phosphorylated Smad-2/3 (p-Smad2/3), a TGF-β signaling molecule, and asporin. MethodsTMJ-OA was induced in a mouse model through unilateral partial discectomy. Micro-computed tomography (micro-CT) and safranin-O staining were performed to morphologically and histologically evaluate the degeneration of the head of mandible caused by TMJ-OA. IHC staining for TGF-β, p-Smad2/3, and asporin was performed to evaluate the changes in protein expression. ResultsIn the experimental group, three-dimensional (3D) morphometry revealed an enlarged head of mandible and safranin-O staining showed degeneration of cartilage tissue in the early stages of TMJ-OA compared to the control group. IHC staining revealed that TGF-β, p-Smad2/3, and asporin expression increased in the head of mandible cartilage before the degeneration of cartilage tissue, and subsequently decreased for a short period. ConclusionThe findings suggested a negative feedback relationship between the expression of asporin and the TGF-β/Smad transduction pathway, which may be involved in the degeneration of the head of mandible in the early stages of TMJ-OA. Asporin is a potential biomarker of the early stages of TMJ-OA, which ultimately leads to the irreversible degeneration of TMJ tissues.

Integrating Network Pharmacology and Experimental Validation to Decipher the Mechanism of Action of Astragalus-Atractylodes Herb Pair in Treating Hepatocellular Carcinoma.

Traditional Chinese medicine (TCM) therapy is an important means to treat hepatocellular carcinoma (HCC), Astragalus (Latin name: Hedysarum Multijugum Maxim; Chinese name: Huangqi, HQ) and Atractylodes (Latin name: Atractylodes Macrocephala Koidz; Chinese name: Baizhu, BZ) (HQBZ), a classic herb pair, is often used in combination to HCC. However, the main components and potential mechanisms of HQBZ therapy in HCC remain unclear. This study aimed to identify the potential active ingredients and molecular mechanisms of action of HQBZ in HCC treatment. The HQBZ-Compound-Target-HCC network and HQBZ-HCC transcriptional regulatory network were constructed to screen the core active compound components and targets of HQBZ therapy for HCC. Molecular docking techniques are used to verify the stability of binding core active compound components to targets. GO and KEGG enrichment analysis were used to explore the signaling pathway of HQBZ in HCC treatment, the mechanism of HQBZ treatment of HCC was verified based on in vivo H22 tumor bearing mice and in vitro cell experiments. Network pharmacology and molecular docking studies showed that HQBZ treatment of HCC was related to the targeted regulation of IL-6 and STAT3 by the active compound biatractylolide, KEGG pathway enrichment analysis suggest that HQBZ may play a role in the treatment of HCC through IL-6/STAT3 signaling pathway. In vitro experiment results proved that HQBZ could regulate IL-6/STAT3 signaling pathway transduction on CD8+T cells, inhibit CD8+T cell exhaustion and restore the function of exhausted CD8+T cells. In vivo experiment results proved that HQBZ can regulate IL-6/STAT3 signaling pathway transduction in H22 liver cancer model mouse tumor tissue, increased the proportion of tumor infiltrating CD8+T cells. This study found that HQBZ may play a therapeutic role in HCC by targeting IL-6 and STAT3 through biatractylolide, its mechanism of action is related to regulating IL-6/STAT3 signaling pathway, reversing T cell failure and increasing tumor infiltration CD8+T cells.

Ginsenoside Rg3 combined with near-infrared photothermal reversal of multidrug resistance in breast cancer MCF-7/ADR cells.

Adriamycin (ADR) is a frequently employed chemotherapeutic agent for the management of breast cancer. Nevertheless, multidrug resistance (MDR) can impair its therapeutic efficacy in breast cancer. MDR is characterized by increased expression of the P-glycoprotein (P-gp) efflux pump, up-regulation of anti-apoptotic proteins, and downregulation of pro-apoptotic proteins. Consequently, inhibition of ATP-binding cassette (ABC) transporter proteins has been deemed the most efficacious approach to overcome MDR. In this study, we used MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide), Western blots, flow cytometry, immunofluorescence, and constructed xenograft tumors to investigate whether ginsenoside Rg3-near-infrared photothermal (Rg3-NIR) combination reversed multidrug resistance in MCF-7/ADR breast cancer. Invivo and invitro experiments, the results showed that Rg3-NIR co-treatment was effective in inducing the apoptosis of MCF-7/ADR breast cancer cells. This was achieved by reversing the expression of drug resistance-associated proteins, while also inhibiting cell proliferation, migration, and epithelial-mesenchymal transition (EMT) processes via attenuation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway transduction. Ginsenoside Rg3 combined with near-infrared photothermal therapy (NIR) effectively reverses multidrug resistance in breast cancer MCF-7/ADR cells, providing a new therapeutic strategy for breast cancer drug resistance.

The Metabolism, Detrimental Effects, and Signal Transduction Mechanism of Reactive Oxygen Species in Plants under Abiotic Stress

Plants are a major source of bio based materials, and their productivity is significantly impacted by environmental adversities with the continuous deterioration of the environment. The disruption of reactive oxygen species (ROS) production and scavenging balance is a common consequence of various abiotic stresses in plants, resulting in the excessive accumulation of ROS. However, it is crucial to acknowledging the dual role of ROS, acting both as harmful substances and signaling molecules. ROS can interact with membrane proteins, initiating a chain reaction of membrane lipid peroxidation. This process leads to a decrease in membrane lipid unsaturation and fluidity, as well as an increase in membrane permeability. Inhibited enzyme activity even lead to loss of protein function, caused DNA damage and mutations, blocked DNA replication and transcription, eventually leading to cell death. This can result in significant reductions in crop yield and biomass in bio based agricultural production. ROS also played vital role in signal molecule transduction in the process of plant resistance to stress, and worked in concert with other signal molecules to induce the stress resistance genes’ expression and enhance plant resistance. Hereto, scavenging mechanism for ROS in plants is of the essence to regulate the concentration of ROS, thus determining which role ROS play. The thermal dissipation of excess light energy effectively avoids ROS production, and the enzymatic and non-enzymatic antioxidant defense systems in plants work cooperatively to clear excessive ROS. This review provides a comprehensive summary of the production pathway, detrimental effects, scavenging mechanism and signal transduction of ROS in plants under abiotic stress.

Integrative proteomic and transcriptomic analysis in the female goat ovary to explore the onset of puberty

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

S100a9 might act as a modulator of the Toll-like receptor 4 transduction pathway in chronic rhinosinusitis with nasal polyps

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including “positive regulation of intracellular signal transduction”, “arachidonic acid metabolic process”, “spermatogenesis” and “negative regulation of cellular protein metabolic process”. Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.

Inducing Circularly Polarized Single-Photon Emission via Chiral-Induced Spin Selectivity.

One of the central aims of the field of spintronics is the control of individual electron spins to effectively manage the transmission of quantized data. One well-known mechanism for controlling electronic spin transport is the chiral-induced spin-selectivity (CISS) effect in which a helical nanostructure imparts a preferential spin orientation on the electronic transport. One potential application of the CISS effect is as a transduction pathway between electronic spin and circularly polarized light within nonreciprocal photonic devices. In this work, we identify and quantify the degree of chiral-induced spin-selective electronic transport in helical polyaniline films using magnetoconductive atomic force microscopy (mcAFM). We then induce circularly polarized quantum light emission from CdSe/CdS core/shell quantum dots placed on these films, demonstrating a degree of circular polarization of up to ∼21%. Utilizing time-resolved photoluminescence microscopy, we measure the radiative lifetime difference associated with left- and right-handed circular polarizations of single emitters. These lifetime differences, in combination with Kelvin probe mapping of the variation of surface potential with magnetization of the substrate, help establish an energy level diagram describing the spin-dependent transport pathways that enable the circularly polarized photoluminescence.

LncRNA Profiling of Exosomes and Its Communication Role in Regulating Silica-Stimulated Macrophage Apoptosis and Fibroblast Activation.

Long-term silica particle exposure leads to interstitial pulmonary inflammation and fibrosis, called silicosis. Silica-activated macrophages secrete a wide range of cytokines resulting in persistent inflammation. In addition, silica-stimulated activation of fibroblast is another checkpoint in the progression of silicosis. The pathogenesis after silica exposure is complex, involving intercellular communication and intracellular signaling pathway transduction, which was ignored previously. Exosomes are noteworthy because of their crucial role in intercellular communication by delivering bioactive substances, such as lncRNA. However, the expression profile of exosomal lncRNA in silicosis has not been reported yet. In this study, exosomes were isolated from the peripheral serum of silicosis patients or healthy donors. The exosomal lncRNAs were profiled using high-throughput sequencing technology. Target genes were predicted, and functional annotation was performed using differentially expressed lncRNAs. Eight aberrant expressed exosomal lncRNAs were considered to play a key role in the process of silicosis according to the OPLS-DA. Furthermore, the increased expression of lncRNA MSTRG.43085.16 was testified in vitro. Its target gene PARP1 was critical in regulating apoptosis based on bioinformatics analysis. In addition, the effects of exosomes on macrophage apoptosis and fibroblast activation were checked based on a co-cultured system. Our findings suggested that upregulation of lncRNA MSTRG.43085.16 could regulate silica-induced macrophage apoptosis through elevating PARP1 expression, and promote fibroblast activation, implying that the exosomal lncRNA MSTRG.43085.16 might have potential as a biomarker for the early diagnosis of silicosis.

Roles of ubiquitin-specific proteases in inflammatory diseases.

Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.

Contribution of changes in the orexin system and energy sensors in the brain in depressive disorder - a study in an animal model

BackgroundMaternal elevated glucocorticoid levels during pregnancy can affect the developing fetus, permanently altering the structure and function of its brain throughout life. Excessive action of these hormones is known to contribute to psychiatric disorders, including depression.MaterialsThe study was performed in a rat model of depression based on prenatal administration of dexamethasone (DEX) in late pregnancy (0.1 mg/kg, days 14–21). We evaluated the effects of prenatal DEX treatment on the cognition and bioenergetic signaling pathways in the brain of adult male rats, in the frontal cortex and hippocampus, and in response to stress in adulthood, using behavioral and biochemical test batteries.ResultsWe revealed cognitive deficits in rats prenatally treated with DEX. At the molecular level, a decrease in the orexin A and orexin B levels and downregulation of the AMPK-SIRT1-PGC1α transduction pathway in the frontal cortex of these animals were observed. In the hippocampus, a decreased expression of orexin B was found and changes in the MR/GR ratio were demonstrated. Furthermore, an increase in HDAC5 level triggered by the prenatal DEX treatment in both brain structures and a decrease in MeCP2 level in the hippocampus were reported.ConclusionsOur study demonstrated that prenatal DEX treatment is associated with cognitive dysfunction and alterations in various proteins leading to metabolic changes in the frontal cortex, while in the hippocampus adaptation mechanisms were activated. The presented results imply that different pathophysiological metabolic processes may be involved in depression development, which may be useful in the search for novel therapies.

The Roles of Mepiquate Chloride and Melatonin in the Morpho-Physiological Activity of Cotton under Abiotic Stress.

Cotton growth and yield are severely affected by abiotic stress worldwide. Mepiquate chloride (MC) and melatonin (MT) enhance crop growth and yield by reducing the negative effects of abiotic stress on various crops. Numerous studies have shown the pivotal role of MC and MT in regulating agricultural growth and yield. Nevertheless, an in-depth review of the prominent performance of these two hormones in controlling plant morpho-physiological activity and yield in cotton under abiotic stress still needs to be documented. This review highlights the effects of MC and MT on cotton morpho-physiological and biochemical activities; their biosynthetic, signaling, and transduction pathways; and yield under abiotic stress. Furthermore, we also describe some genes whose expressions are affected by these hormones when cotton plants are exposed to abiotic stress. The present review demonstrates that MC and MT alleviate the negative effects of abiotic stress in cotton and increase yield by improving its morpho-physiological and biochemical activities, such as cell enlargement; net photosynthesis activity; cytokinin contents; and the expression of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase. MT delays the expression of NCED1 and NCED2 genes involved in leaf senescence by decreasing the expression of ABA-biosynthesis genes and increasing the expression of the GhYUC5, GhGA3ox2, and GhIPT2 genes involved in indole-3-acetic acid, gibberellin, and cytokinin biosynthesis. Likewise, MC promotes lateral root formation by activating GA20x genes involved in gibberellin catabolism. Overall, MC and MT improve cotton's physiological activity and antioxidant capacity and, as a result, improve the ability of the plant to resist abiotic stress. The main purpose of this review is to present an in-depth analysis of the performance of MC and MT under abiotic stress, which might help to better understand how these two hormones regulate cotton growth and productivity.