Putative Key Factor Research Articles

Maize Dek51 encodes a DEAD-box RNA helicase essential for pre-rRNA processing and seed development

Pre-rRNA processing is essential to ribosome biosynthesis. However, the processing mechanism is not fully understood in plants. Here, we report a DEAD-box RNA helicase DEK51 that mediates the 3' end processing of 18S and 5.8S pre-rRNA in maize (Zea mays L.). DEK51 is localized in the nucleolus, and loss of DEK51 arrests maize seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA. DEK51 interacts with putative key factors in nuclear RNA exosome-mediated pre-rRNA processing, including ZmMTR4, ZmSMO4, ZmRRP44A, and ZmRRP6L2. This suggests that DEK51 facilitates pre-rRNA processing by interacting with the exosome. Loss of ZmMTR4 function arrests seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA, similar to dek51. DEK51 also interacts with endonucleases ZmUTP24 and ZmRCL1, suggesting that it may also be involved in the cleavage at site A2. These results show the critical role of DEK51 in promoting 3' end processing of pre-rRNA.

Liangxue-Qushi-Zhiyang Decoction Ameliorates DNCB-Induced Atopic Dermatitis in Mice through the MAPK Signaling Pathway Based on Network Pharmacology.

The traditional prescription of Liangxue-Qushi-Zhiyang decoction (LQZ) has been demonstrated to be efficacious in treating atopic dermatitis (AD), a chronic inflammatory skin disorder marked by intense itching, redness, rashes, and skin thickening. Nevertheless, there has been an inadequate systematic exploration of the potential targets, biological processes, and pathways for AD treatment through LQZ. The study objective was to evaluate the efficacy and possible mechanism of LQZ in AD mice. In our study, we identified the primary compounds of LQZ, analyzed hub targets, and constructed a network. Subsequently, the predicted mechanisms of LQZ in AD were experimentally studied and validated in vivo, as determined by network pharmacological analysis. A total of 80 serum components of LQZ were identified through ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS), among which 49 compounds were absorbed into the bloodstream. Our results indicated that LQZ targets six putative key factors in the MAPK signaling pathway, which play essential roles in AD, namely, EGFR, p-MAPK1/3, p-MAPK14, IL-1β, IL-6, and TNF-α. We observed spleen coefficient, dermatitis scores, and ear thickness were all downregulated in 2,4-dinitrochlorobenzene (DNCB)-induced mice after LQZ treatment. Histological analysis of the dorsal and ear skin further revealed that LQZ significantly decreased skin inflammation, epidermal thickness, and mast cell numbers compared to the DNCB group. Our study demonstrated the effectiveness of LQZ in reducing epidermal and dermal damage in a mouse model of AD. Furthermore, our findings suggest that downregulating the MAPK signaling pathway could be a potential therapeutic strategy for the treatment of AD.

Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders?

Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. Although the majority of infected individuals remain asymptomatic, this bacterium colonizes the gastric mucosa causing the development of various clinical conditions as peptic ulcers, chronic gastritis and gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas, but complications are not limited to gastric ones. Extradigestive pathologies, including metabolic disturbances such as diabetes, obesity and nonalcoholic fatty liver disease, have also been associated with H. pylori infection. However, the underlying mechanisms connecting H. pylori with extragastric metabolic diseases needs to be clarified. Notably, the latest studies on the topic have confirmed that H. pylori infection modulates gut microbiota in humans. Damage in the gut bacterial community (dysbiosis) has been widely related to metabolic dysregulation by affecting adiposity, host energy balance, carbohydrate metabolism, and hormonal modulation, among others. Taking into account that Type 2 diabetic patients are more prone to be H. pylori positive, gut microbiota emerges as putative key factor responsible for this interaction. In this regard, the therapy of choice for H. pylori eradication, based on proton pump inhibitor combined with two or more antibiotics, also alters gut microbiota composition, but consequences on metabolic health of the patients has been scarcely explored. Recent studies from our group showed that, despite decreasing gut bacterial diversity, conventional H. pylori eradication therapy is related to positive changes in glucose and lipid profiles. The mechanistic insights explaining these effects should also be addressed in future research. This review will deal with the role of gut microbiota as the linking factor between H. pylori infection and metabolic diseases, and discussed the impact that gut bacterial modulation by H. pylori eradication treatment can also have in host’s metabolism. For this purpose, new evidence from the latest human studies published in more recent years will be analyzed.

Quantification of aromatase binding in the female human brain using [11 C]cetrozole positron emission tomography.

Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND ), with cerebellum as reference region, can be used to estimate [11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach.

Therapeutic Mechanistic Studies of ShuFengJieDu Capsule in an Acute Lung Injury Animal Model Using Quantitative Proteomics Technology.

ShuFengJieDu capsule (SFJDC), a traditional Chinese medicine (TCM) that contains eight medicinal herbs, has been extensively utilized for the treatment of acute lung injury (ALI) and respiratory infections for more than 30 years in China. SFJDC has also been listed in the official guidelines of the China Food and Drug Administration (CFDA) due to its stable clinical manifestations. However, the underlying mechanism of SFJDC during ALI repair remains unclear. In the present study, we explored the protective and therapeutic mechanisms of SFJDC in a rat model by performing qualitative and label-free quantitative proteomics studies. After establishing lipopolysaccharide (LPS)-induced ALI rat models, we profiled macrophage cells isolated from freshly resected rat lung tissues derived from ALI models and ALI rat lung tissue sections using a high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) shotgun proteomics approach to identify changes in the expression levels of proteins of interest. On the basis of our proteomics results and the results of a protein dysregulation analysis of ALI rat lung tissues and rat lung macrophages, AKT1 was selected as a putative key factor that may play an important role in mediating the effects of SFJDC treatment during ALI progression. Follow-up validation studies demonstrated that AKT1 expression effectively regulates various ALI-related molecules, and Gene Ontology analysis indicated that SFJDC-treated ALI rat macrophages were influenced by AKT1-based networks. Gain- and loss-of-function analyses following lentivirus-AKT1 or lentivirus-si-AKT1 infection in macrophages also indicated that AKT1 was essential for the development of ALI due to its ability to regulate oxidative stress, apoptosis, or inflammatory responses. In summary, SFJDC effectively modulated anti-inflammatory and immunomodulation activity during ALI, potentially due to AKT1 regulation during ALI progression. New insights into SFJDC mechanisms may facilitate the development of novel pharmaceutical strategies to control the expression of inflammatory factors.

Dietary fatty acids affect semen quality: a review.

Mammalian spermatozoa are characterized by a high proportion of polyunsaturated fatty acids (PUFA) which play a crucial role in fertilization. This review focuses on analysis of sperm fatty acid profiles and the effects of omega-3, saturated and trans dietary and sperm fatty acids on sperm parameters. Two major points have been pivotal points of investigation in the field of sperm fatty acid profiles: first, the comparison between fatty acid profiles of fertile and infertile men and second, the effect of dietary fatty acids on sperm fatty acid profiles as well as sperm quality and quantity. Docosahexaenoic acid (DHA, C22:6n-3), and palmitic acid (C16:0) are the predominant PUFA and saturated fatty acids, respectively, in human sperm cells. Higher levels of DHA are concentrated on the sperm's head or tail varying among different species. However, the human sperm head contains a higher concentration of DHA. Dietary fatty acids influence on sperm fatty acid profiles and it seems that sperm fatty acid profiles are most sensitive to dietary omega-3 PUFA. Although improvements in sperm parameters are a response to omega-3 sources after more than 4 weeks of supplementation in the male diet, time-dependent and dose-dependent responses may explain the failure in some experiments. In human spermatozoa, elevated saturated or trans fatty acid concentration and a low DHA level is a concern. The regulations of the sperm fatty acid mean melting point as well as expression regulation of peroxisome proliferator-activated receptor gamma (PPARG) alongside with spermatozoon assembly, anti-apoptosis effects, eicosanoid formation, and hormone activity are the putative key factors that induce a response by inclusion of omega-3 PUFA.

Systemic Analysis of Tumor Cell-Induced Endothelial Calcium Signaling and Junction Disassembly

It has been shown in our previous study that melanoma cells induce junction disassembly in the manner related to phospholipase C-calcium activation. In light of this observation, we have developed a mathematical model of the signaling pathway and adapted multi-parametric sensitivity analysis (MPSA) to identify important parameters in the model, which examines tumor cell-induced calcium mobilization in endothelial cells. The objective functions, with respect to individual parameters, were generated for the calcium mobilization model and MPSA was performed according to the function. The results showed that sarco/endoplasmic reticulum calcium ATPase was one of the putative key factors in regulating calcium mobilization. The model is a proof of concept of systemic analysis of a signaling network, and the results may have practical applications in describing how endothelial cells respond to tumor cells. Taken together, we have devised numerical means to macroscopically study roles of calcium signaling in endothelial cells in contact with metastatic tumor cells.

FGF8 signaling patterns the telencephalic midline by regulating putative key factors of midline development

FGF8 has been reported to act as a primary regulator of neocortical patterning along the anteroposterior (AP) axis in the mouse telencephalon, and disruption of FGF signaling causes distortion of molecular arealization along the AP axis. Since hypoplasia of midline structures is observed in Fgf8 mutant mice, FGF8 is also postulated to be involved in telencephalic midline development. In this study we analyzed the role of FGF8 in midline development by means of gain-of-function and loss-of-function experiments. The results showed that FGF8 up-regulates the expression of transcription factor (TF) genes, including putative key factors involved in midline development. Although FGF8 had been thought to act downstream of SHH signaling, ectopic FGF8 up-regulates the expression of midline TF genes in Shh null mice, suggesting that FGF signaling acts as an upstream positive regulator of midline TFs during midline development independently of SHH.

Diversity and distribution of lichens in relation to altitude within a protected biodiversity hot spot, north-east India

Abstract:A study of the diversity and distribution of lichens at 10 sites within the Mehao Wildlife Sanctuary in Arunachal Pradesh, India, revealed 177 species, belonging to 71 genera and 35 families. The Sanctuary exhibited almost all the habit and habitat groups of lichens within its climatically heterogenous and altitudinally (400–2700 m) varied landscape. Among the different habitat groups, obligately corticolous lichens were dominant (133 species), followed by facultatively corticolous lichens (occurring on both rock and bark; 25 species), saxicolous lichens (17 species) and terricolous lichens (2 species). The corticolous habitat group was dominated by crustose species while saxicolous and terricolous groups were made up of mostly fruticose species. A substantial number of species (77) occurred at single sites only, and each of the 10 sites supported a distinct lichen assemblage. Altitude and humidity were the putative key factors controlling the diversity and distribution of lichens within the Sanctuary. The mid altitude range 1400–1600 m had the greatest lichen diversity, which showed a unimodal pattern in relation to altitude.

Cardiac autonomic balance in small-for-gestational-age neonates

The cardiac sympathetic nervous system is one putative key factor involved in the intrauterine programming of adult cardiovascular disease. We therefore analyzed cardiac autonomic system activity in small for gestational age (SGA) neonates. Heart rate variability (HRV) from 24-h ECG recordings were analyzed for time-domain and frequency-domain parameters in 27 SGA neonates [median 261 (240-283) days of gestation] compared with 27 appropriate for gestational age (AGA) neonates [median 270 (239-293) days of gestation]. In addition, salivary alpha-amylase levels were analyzed during resting conditions and in response to a pain-induced stress event in 18 SGA [median 266 (240-292) days of gestation] and 34 AGA [median 271 (240-294) days of gestation] neonates. Overall HRV was not significantly different in SGA neonates compared with AGA neonates (SD of all valid NN intervals: P = 0.14; triangular index: P = 0.29), and the sympathovagal balance [low frequency (LF)/high frequency (HF)] was similar (P = 0.62). Parameters mostly influenced by sympathetic activity did not reveal significant differences: (SD of the average of valid NN intervals: P = 0.27; average of the hourly means of SDs of all NN intervals: P = 0.66, LF: P = 0.83) as well as vagal tone-influenced parameters were unaltered (average of the hourly square root of the mean of the sum of the squares of differences between adjacent NN intervals: P = 0.59; proportion of pairs of adjacent NN intervals differing by >50 ms: P = 0.93; HF: P = 0.82). Median resting levels for alpha-amylase were not significantly different in SGA neonates (P = 0.13), and a neonatal stress stimulus revealed similar stress response patterns (P = 0.29). HRV and salivary alpha-amylase levels as indicators of cardiac autonomic activity were not altered in SGA neonates compared with AGA neonates. Thus, it appears that the intrauterine activation of the sympathetic system in SGA fetuses does not directly persist into postnatal life, and neonatal sympathovagal balance appears to be preserved.

Salt-Induced Nephropathy in Obese Spontaneously Hypertensive Rats Via Paradoxical Activation of the Mineralocorticoid Receptor

Aldosterone is implicated in the pathogenesis of proteinuria and chronic kidney disease. We previously demonstrated the contribution of elevated serum aldosterone in the early nephropathy of SHR/NDmcr-cp (SHR/cp), a rat model of metabolic syndrome. In the present study, we investigated the effect of salt loading on renal damage in SHR/cps and explored the underlying mechanisms. SHR/cps fed a high-sodium diet for 4 weeks developed severe hypertension, massive proteinuria, and advanced renal lesions. High salt also worsened glomerular podocyte impairment. Surprisingly, selective mineralocorticoid receptor (MR) antagonist eplerenone dramatically ameliorated the salt-induced proteinuria and renal injury in SHR/cps. Although salt loading reduced circulating aldosterone, it increased nuclear MR and expression of aldosterone effector kinase Sgk1 in the kidney. Gene expressions of transforming growth factor-beta1 and plasminogen activator inhibitor-1 were also enhanced in the kidneys of salt-loaded SHR/cps, and eplerenone completely inhibited these injury markers. To clarify the discrepancy between decreased aldosterone and enhanced MR signaling by salt, we further investigated the role of oxidative stress, a putative key factor mediating salt-induced tissue damage. Interestingly, antioxidant Tempol attenuated the salt-evoked MR upregulation and Sgk1 induction and alleviated proteinuria and renal histological abnormalities, suggesting the involvement of oxidative stress in salt-induced MR activation. MR activation by salt was not attributed to increased serum corticosterone or reduced 11beta-hydroxysteroid dehydrogenase type 2 activity. In conclusion, sodium loading exacerbated proteinuria and renal injury in metabolic syndrome rats. Salt reduced circulating aldosterone but caused renal MR activation at least partially via induction of oxidative stress, and eplerenone effectively improved the nephropathy.

Expression, Localization, and Significance of Vascular Permeability/Vascular Endothelial Growth Factor in Nasal Polyps

The exact etiologic mechanisms leading to the formation of nasal polyps have remained largely obscure. A key phenomenon of this specific type of chronic inflammatory disease in nasal respiratory mucosa is remarkable edema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) plays an important role in inducing angiogenesis and modulating capillary permeability. To study the expression and localization of VPF/ VEGF as a putative key factor in nasal polyp development. Specimens of nasal polyps (n = 12) were harvested during endonasal sinus surgery in patients with polypous chronic rhinosinusitis. Specimens of healthy nasal respiratory mucosa (n = 12) served as controls and were obtained from inferior turbinates of patients undergoing surgery for nasal obstruction without signs and symptoms of inflammatory disease. Frozen sections were immunohistochemically stained for VPF/VEGF and quantitatively analyzed, using computer-based image analysis. The expression of VPF/VEGF in specimens of nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps was significantly stronger than in specimens of healthy nasal mucosa of controls. VPF/VEGF in polypous tissue was mainly localized in vascular endothelial cells, in basal membranes and perivascular spaces, and in epithelial cells. Conclusion: The markedly increased expression in nasal polyps as opposed to healthy nasal mucosa suggests that VPF/VEGF may play a significant role in both the formation of nasal polyps and in the induction of heavy tissue edema. This finding is discussed with respect to the differential expression of cyclooxygenase (COX) isoenzymes-1 and -2 (COX-1 and COX-2) in nasal polyps.

Effects of phytosulfokine-α on growth and tropane alkaloid production in transformed roots of Atropa belladonna

Phytosulfokine (PSK)-α is a sulphated pentapeptide, isolated fromthe medium of cultured Asparagus officinalis mesophyllcells, that promotes cell proliferation. It is a putative key factor inconditioned medium required for the growth of low-density plant cell cultures.The present study investigates the effect of PSK-α on growth and tropanealkaloid production in Atropa belladonna hairy rootstransformed with Agrobacteriumrhizogenes (MAFF 03-01724). Although the growth rates ofhairy roots cultured in medium with orwithout PSK-α for 4 weeks did not show any differences, the productivityof tropane alkaloids, especially of hyoscyamine, was enhanced by10−7 or 10−8 M PSK-α. Inaddition, the content of tropane alkaloids in transformed roots treated withPSK-α was 1.4 times higher than that of untreated roots after 4 weeks ofculture. The time course of growth and tropane alkaloid production inAtropa belladonna transformed roots suggested thatPSK-α influenced the growth of transformed roots during the activegrowingphase, but not tropane alkaloid production.