Protective Role Research Articles

Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study.

Numerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, a clear causative association between the gut microbiota and GERD has yet to be definitively ascertained, given the presence of confounding variables. The genome-wide association study (GWAS) pertaining to the microbiome, conducted by the MiBioGen consortium and comprising 18,340 samples from 24 population-based cohorts, served as the exposure dataset. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. The inverse variance-weighted (IVW) method was performed as a primary analysis, the other four methods were used as supporting analyses. Furthermore, sensitivity analyses encompassing Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and leave-one-out methodology were carried out to identify potential heterogeneity and horizontal pleiotropy. Ultimately, a reverse MR assessment was conducted to investigate the potential for reverse causation. The IVW method's findings suggested protective roles against GERD for the Family Clostridiales Vadin BB60 group (P = 0.027), Genus Lachnospiraceae UCG004 (P = 0.026), Genus Methanobrevibacter (P = 0.026), and Phylum Actinobacteria (P = 0.019). In contrast, Class Mollicutes (P = 0.037), Genus Anaerostipes (P = 0.049), and Phylum Tenericutes (P = 0.024) emerged as potential GERD risk factors. In assessing reverse causation with GERD as the exposure and gut microbiota as the outcome, the findings indicate that GERD leads to dysbiosis in 13 distinct gut microbiota classes. The MR results' reliability was confirmed by thorough assessments of heterogeneity and pleiotropy. For the first time, the MR analysis indicates a genetic link between gut microbiota abundance changes and GERD risk. This not only substantiates the potential of intestinal microecological therapy for GERD, but also establishes a basis for advanced research into the role of intestinal microbiota in the etiology of GERD.

Dapagliflozin alleviates high glucose-induced injury of endothelial cells via inducing autophagy.

Hyperglycaemia is a key factor in the progression of diabetes complications. Dapagliflozin (DAPA), a new type of hypoglycaemicagent, has been shown to play an important role in anti-apoptotic, anti-inflammatory and antioxidant activities. Previous studies have demonstrated an endothelial protective effect of DAPA, but the underlying mechanism was still unclear. Autophagy is a homeostatic cellular mechanism that circulates unfolded proteins and damaged organelles through lysosomal dependent degradation. In this study, we aimed to investigate whether DAPA plays a protective role against high glucose (HG)-induced endothelial injury through regulating autophagy. The results showed that DAPA treatment resulted in increased cell viability. Additionally, DAPA treatment decreased interleukin (IL)-1β, IL-6, and tumour necrosis factor-α levels in endothelial cells subjected to HG conditions. We observed that HG inhibited autophagy, and DAPA increased the autophagy level by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. Chloroquine reversed all of these beneficial effects as an autophagy inhibitor. In summary, the endothelial protective effect of DAPA in HG can be attributed in part to its role in activating of autophagy via the AKT/mTOR signalling pathway. Therefore, suggesting that the activation of autophagy by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.

The role of desmoglein-2 in kidney disease

Desmosomes are multi-protein cell-cell adhesion structures supporting cell stability and mechanical stress resilience of tissues; best described in skin and heart. The kidney is exposed to various mechanical stimuli and stress, yet little is known about kidney desmosomes. In healthy kidneys, we found desmosomal proteins located at the apical-junctional complex in tubular epithelial cells. In four different animal models and patient biopsies with various kidney diseases, desmosomal components were significantly upregulated and partly miss-localized outside of the apical-junctional complexes along the whole lateral tubular epithelial cell membrane. The most upregulated component was desmoglein-2 (Dsg2). Mice with constitutive tubular epithelial cell-specific deletion of Dsg2 developed normally and other desmosomal components were not altered in these mice. When challenged with different types of tubular epithelial cell injury (unilateral ureteral obstruction, ischemia-reperfusion, and 2,8-dihydroxyadenine crystal nephropathy) we found increased tubular epithelial cell apoptosis, proliferation, tubular atrophy, and inflammation compared to wild type mice in all models and time points. In vitro, silencing DSG2 via siRNA weakened cell-cell adhesion in HK-2 cells and increased cell death. Thus, our data show a prominent upregulation of desmosomal components in tubular cells across species and diseases and suggest a protective role of Dsg2 against various injurious stimuli.

Application of green synthesized copper oxide nanoparticles for effective mitigation of Fusarium wilt disease in roots of Cicerarietinum

The study investigated the impact of copper oxide nanoparticles (CuONPs) on Fusarium wilt in chickpea. CuONPs, synthesized using coffee powder, were subjected to washing and sonication using Milli-Q water as the solvent during the purification process. Subsequently the nanoparticles were characterized through UV–vis spectroscopy, DLS, Zeta Potential and FTIR analysis. The NPs exhibited a size range of 85–100 nm with a zeta potential of −25.3 mV. Seven days old chickpea seedlings treated with different concentrations of CuONP (10, 25, 50 ppm) via root immersion showed a significant reduction in Fusarium infection severity. Treatment with 10 and 25 ppm CuONPs led to a remarkable 74.5% and 50% decrease in wilt incidence, along with increased root and shoot length, protein, tannin, phenolics, and flavonoid content in chickpea seedlings, grown in Fusarium infected soil. Enzyme activity (PAL, PPO, NR) was enhanced, while proline, H2O2, and MDA content decreased in 10 and 25 ppm CuONPs treated seedlings. A reduced activity of APX and SOD was also recorded in 10 and 25 ppm CuONPs treated seedlings. Chlorophyll content increased by 50.08% in 10 ppm treated seedlings but decreased with 25 and 50 ppm. The findings emphasize the protective role of copper oxide nanoparticles (CuONPs) at a lower concentration of 10 ppm against Fusarium wilt disease. This protective effect is manifested through the reduction of oxidative stress, decreased wilt incidence, and an increased biomass.

LncRNA-MIAT rs9625066 polymorphism could be a potential biomarker for ischemic stroke.

Ischemic stroke (IS) is a common and serious neurological condition that is highly fatal but so far no early diagnostic markers are available. Myocardial infarction-associated transcript (MIAT) is a long non-coding RNA (lncRNA) that could lead to IS by inducing autophagy and apoptosis in neuronal cells. However, there has been no report on the link between susceptibility to IS and the single-nucleotide polymorphisms (SNPs) of MIAT. This study aimed to investigate the association between MIAT gene polymorphisms and IS risk. A total of 320 IS patients and 310 age-, sex- and race-matched controls were included in this study. Four polymorphisms (rs2157598, rs5761664, rs1894720, and rs9625066) were genotyped by using SNPscan technique. Among the 4 polymorphisms of MIAT, only rs9625066 was associated with IS risk (CA vs. CC: adjusted OR = 0.55, 95% CI, 0.37-0.85, P = 0.006; AA vs. CC: adjusted OR = 0.39, 95% CI, 0.16-0.94, P = 0.036; (AA + CA vs. CC: adjusted OR = 0.53, 95% CI, 0.35-0.80, P = 0.002; A vs. C adjusted OR = 0.59, 95% CI, 0.42-0.82, P = 0.002). Haplotype analysis showed a 1.32-fold increase (95% CI, 1.05-1.67, P = 0.017) in IS risk for rs2157598-rs5761664-rs1894720-rs9625066 (A-C-G-C). Logistic regression analysis identified some independent impact factors for IS including rs9625066 AA/AC, TC, TG, HDL-C (P < 0.05). The rs9625066 polymorphism of MIAT might be associated with IS susceptibility in Chinese population, in which AA/CA plays a protective role in IS, whereas the CC genotype increases the risk of developing IS, suggesting it might be a marker predictive of IS risk.

MRPS9-Mediated Regulation of the PI3K/Akt/mTOR Pathway Inhibits Neuron Apoptosis and Protects Ischemic Stroke.

Neuronal apoptosis is crucial in the pathophysiology of ischemic stroke (IS), albeit its underly24ing mechanism remaining elusive. Investigating the mechanism of neuronal apoptosis in the context of IS holds substantial clinical value for enhancing the prognosis of IS patients. Notably, the MRPS9 gene plays a pivotal role in regulating mitochondrial function and maintaining structural integrity. Utilizing bioinformatic tactics and the extant gene expression data related to IS, we conducted differential analysis and weighted correlation network analysis (WGCNA) to select important modules. Subsequent gene interaction analysis via the STRING website facilitated the identification of the key gene-mitochondrial ribosomal protein S9 (MRPS9)-that affects the progression of IS. Moreover, possible downstream signaling pathways, namely PI3K/Akt/mTOR, were elucidated via Kyoto Encyclopedia of Gene and Genomes (KEGG) and Gene Ontology (GO) pathway analysis. Experimental models were established utilizing oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. Changes in gene and protein expression, as well as cell proliferation and apoptosis, were monitored through qPCR, WB, CCK8, and flow cytometry. An OGD/R cell model was further employed to investigate the role of MRPS9 in IS post transfusion of MRPS9 overexpression plasmids into cells. Further studies were conducted by transfecting overexpressed cells with PI3K/Akt/mTOR signaling pathway inhibitor LY294002 to unveil the mechanism of MRPS9 in IS. Bioinformatic analysis revealed a significant underexpression of MRPS9 in ischemic stroke patients. Correspondingly, in vitro experiments with HN cells subjected to OGD/R treatment demonstrated a marked reduction in MRPS9 expression, accompanied by a decline in cell viability, and an increase cell apoptosis. Notably, the overexpression of MRPS9 mitigated the OGD/R-induced decrease in cell viability and augmentation of apoptosis. In animal models, MRPS9 expression was significantly lower in the MCAO/R group compared to the sham surgery group. Further, the KEGG pathway analysis associated MRPS9 expression with the PI3K/Akt/mTOR signaling pathway. In cells treated with the specific PI3K/Akt/mTOR inhibitor LY294002, phosphorylation levels of Akt and mTOR were decreased, cell viability decreased, and apoptosis increased compared to the MRPS9 overexpression group. These findings collectively indicate that MRPS9 overexpression inhibits PI3K/Akt/mTOR pathway activation, thereby protecting neurons from apoptosis and impeding IS progression. However, the PI3K/Akt/mTOR inhibitor LY294002 is capable of counteracting the protective effect of MRPS9 overexpression on neuronal apoptosis and IS. Our observations underscore the potential protective role of MRPS9 in modulating neuronal apoptosis and in attenuating the pathophysiological developments associated with IS. This is achieved through the regulation of the PI3K/Akt/mTOR pathway. These insights forge new perspectives and propose novel targets for the strategic diagnosis and treatment of IS.

Probiotics as modulators of gut-brain axis for cognitive development.

Various microbial communities reside in the gastrointestinal tract of humans and play an important role in immunity, digestion, drug metabolism, intestinal integrity, and protection from pathogens. Recent studies have revealed that the gut microbiota (GM) is involved in communication with the brain, through a bidirectional communication network known as the gut-brain axis. This communication involves humoral, immunological, endocrine, and neural pathways. Gut dysbiosis negatively impacts these communication pathways, leading to neurological complications and cognitive deficits. Both pre-clinical and clinical studies have demonstrated that probiotics can restore healthy GM, reduce intestinal pH, and reduce inflammation and pathogenic microbes in the gut. Additionally, probiotics improve cell-to-cell signaling and increase blood-brain-derived neurotrophic factors. Probiotics emerge as a potential approach for preventing and managing neurological complications and cognitive deficits. Despite these promising findings, the safety concerns and possible risks of probiotic usage must be closely monitored and addressed. This review article provides a brief overview of the role and significance of probiotics in cognitive health.

Linagliptin's impact on lymphatic barrier and lymphangiogenesis in oral cancer with high glucose.

Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier-related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. A CAL-27-LEC co-culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability. Western blotting and RT-qPCR detected protein and mRNA expression under different conditions, respectively. CCK-8, scratch wound healing, and transwell assays revealed cell migration and proliferation. Tube formation experiment tested capacity for endothelial tube formation. Immunohistochemical staining analyzed tissue sections from 43 oral cancer individuals with/without diabetes. In high-glucose co-culture system, we observed increased lymphatic barrier permeability and decreased expression of ZO-1 and occludin, two tight-junction proteins; conversely, the expression of PAR2, a high permeability-related protein, was increased. Following linagliptin treatment, the expression levels of VEGF-C, VEGFR-3, and PAR2 decreased, while those of ZO-1 and occludin increased. Considerably higher levels of LYVE-1 expression in individuals with diabetes than in those without diabetes. By ameliorating the high glucose-induced disruption of the lymphatic endothelial barrier, linagliptin may reduce lymphangiogenesis and exhibit an inhibitory effect on lymphatic metastasis in oral cancer patients with diabetes.

Using vulnerability assessment to characterize coastal protection benefits provided by estuarine habitats of a dynamic intracoastal waterway.

The existence of coastal ecosystems depends on their ability to gain sediment and keep pace with sea level rise. Similar to other coastal areas, Northeast Florida (United States) is experiencing rapid population growth, climate change, and shifting wetland communities. Rising seas and more severe storms, coupled with the intensification of human activities, can modify the biophysical environment, thereby increasing coastal exposure to storm-induced erosion and inundation. Using the Guana Tolomato Matanzas National Estuarine Research Reserve as a case study, we analyzed the distribution of coastal protection services-expressly, wave attenuation and sediment control-provided by estuarine habitats inside a dynamic Intracoastal waterway. We explored six coastal variables that contribute to coastal flooding and erosion-(a) relief, (b) geomorphology, (c) estuarine habitats, (d) wind exposure, (e) boat wake energy, and (f) storm surge potential-to assess physical exposure to coastal hazards. The highest levels of coastal exposure were found in the north and south sections of the Reserve (9% and 14%, respectively) compared to only 4% in the central, with exposure in the south driven by low wetland elevation, high surge potential, and shorelines composed of less stable sandy and muddy substrate. The most vulnerable areas of the central Reserve and main channel of the Intracoastal waterway were exposed to boat wakes from larger vessels frequently traveling at medium speeds (10-20 knots) and had shoreline segments oriented towards the prevailing winds (north-northeast). To guide management for the recently expanded Reserve into vulnerable areas near the City of Saint Augustine, we evaluated six sites of concern where the current distribution of estuarine habitats (mangroves, salt marshes, and oyster beds) likely play the greatest role in natural protection. Spatially explicit outputs also identified potential elevation maintenance strategies such as living shorelines, landform modification, and mangrove establishment for providing coastal risk-reduction and other ecosystem-service co-benefits. Salt marshes and mangroves in two sites of the central section (N-312 and S-312) were found to protect more than a one-quarter of their cross-shore length (27% and 73%, respectively) from transitioning to the highest exposure category. Proposed interventions for mangrove establishment and living shorelines could help maintain elevation in these sites of concern. This work sets the stage for additional research, education, and outreach about where mangroves, salt marshes, and oyster beds are most likely to reduce risk to wetland communities in the region.

IL-4 activates the futile triacylglyceride cycle for glucose utilization in white adipocytes.

The development of cardiometabolic complications during obesity is strongly associated with chronic latent inflammation in hypertrophied adipose tissue (AT). IL-4 is an anti-inflammatory cytokine, playing a protective role against insulin resistance, glucose intolerance and weight gain. The positive effects of IL-4 are associated not only with the activation of anti-inflammatory immune cells in AT, but also with the modulation of adipocyte metabolism. IL-4 is known to activate lipolysis and glucose uptake in adipocytes, but the precise regulatory mechanisms and physiological significance of these processes remain unclear. In this study, we detail IL-4 effects on glucose and triacylglycerides (TAGs) metabolism and propose mechanisms of IL-4 metabolic action in adipocytes. We have shown that IL-4 activates glucose oxidation, lipid droplet (LD) fragmentation, lipolysis and thermogenesis in mature 3T3-L1 adipocytes. We found that lipolysis was not accompanied by fatty acids (FAs) release from adipocytes, suggesting FA re-esterification. Moreover, glucose oxidation and thermogenesis stimulation depended on adipocyte triglyceride lipase (ATGL) activity, but not the uncoupling protein (UCP1) expression. Based on these data, IL-4 may activate the futile TAG-FA cycle in adipocytes, which enhances the oxidative activity of cells and heat production. Thus, the positive effect of IL-4 on systemic metabolism can be the result of the activation of non-canonical thermogenic mechanism in AT, increasing TAG turnover and utilization of excessive glucose.

Body appreciation predicts lower levels of orthorexia nervosa symptoms: Prospective findings

Recent evidence shows that negative body image may be a potential risk factor for symptoms of orthorexia nervosa (ON). However, whether positive body image plays a protective role against symptoms of ON remains unclear. Although prior research has established associations between body appreciation (a core component of positive body image) and ON symptoms, this research is limited to cross-sectional designs, precluding inferences of temporal precedence. Thus, the present study overcomes this limitation by testing whether body appreciation prospectively predicts ON symptoms. Data were analysed from 1253 adult women (M age = 34 years (SD = 9.4), 81.3% Caucasian) who completed the Orthorexia Nervosa Inventory (ONI) and Body Appreciation Scale 2-Short Form (BAS2-SF) at baseline (T1) and at three-month follow-up (T2). Multiple linear regressions were used to test whether body appreciation scores at T1 predicted ONI subscale scores (behaviours, emotions, and impairments) at T2. Results revealed that higher body appreciation scores at T1 significantly predicted decreased scores on each ONI subscale at T2, though effect sizes were small. Findings provide preliminary evidence that body appreciation may protect against ON symptoms. If replicated, efforts to address ON symptoms may be enhanced by promoting body appreciation.

The Hepato and Reno Protective Role of Curcumin against the Alterations in Some Biochemical Parameter and Histological Damage Induced by Monosodium Glutamate in Male Albino Rats

The main objective of current research was to investigate toxicity effect of Monosodium glutamate and protective role of Curcumin on some blood biochemical parameters, body weight gain, relative organ weight and histopathological alterations in liver and kidney tissues in male albino rats. Twenty animals of male rats (Rattus norvegicus), their weight ranged from 111 to 165 gm. The animals were divided into four groups: Each animal group contained five rat, first group was control negative (-ve) administrated distilled water, the second group was control positive (+ve) administrated curcumin, third group was administrated by Monosodium glutamate (MSG) at dose 20 mg per one Kg and the forth group was administrated by Monosodium glutamate (MSG) at dose 20mg/Kg of body weight + curcumin at dose 100 mg per one Kg of body weight. All animal groups were administrated orally about 30 days. The study recorded significant p≥0.05 increment in liver and kidney function parameters included [Alanine transaminase (ALT), Aspartate aminotransferase (AST), Urea and creatinine] after oral administration of animals with MSG and MSG + Curcumin as a comparison with control groups. The study recorded significant decrement p≥0.05 in liver and kidney function parameters included ALT, AST, Urea and creatinine) in group was administrated MSG + Curcumin in comparison with group was administrated MSG only. Additionally, current study revealed histopathological changes in liver and kidney tissue in groups were administrated MSG and MSG+ curcumin compared with + curcumin compared with control groups. Furthermore, the study revealed that curcumin had protective effect and result in slight histopathological changes in liver and kidney tissue by reducing the damage and in group was treated by MSG+ curcumin for 30 days compared with MSG treated group.

The crystal structure of mycothiol disulfide reductase (Mtr) provides mechanistic insight into the specific low-molecular-weight thiol reductase activity of Actinobacteria.

Low-molecular-weight (LMW) thiols are involved in many processes in all organisms, playing a protective role against reactive species, heavy metals, toxins and antibiotics. Actinobacteria, such as Mycobacterium tuberculosis, use the LMW thiol mycothiol (MSH) to buffer the intracellular redox environment. The NADPH-dependent FAD-containing oxidoreductase mycothiol disulfide reductase (Mtr) is known to reduce oxidized mycothiol disulfide (MSSM) to MSH, which is crucial to maintain the cellular redox balance. In this work, the first crystal structures of Mtr are presented, expanding the structural knowledge and understanding of LMW thiol reductases. The structural analyses and docking calculations provide insight into the nature of Mtrs, with regard to thebinding and reduction of the MSSM substrate, in the context of related oxidoreductases. The putative binding site for MSSM suggests a similar binding to that described for the homologous glutathione reductase and its respective substrate glutathione disulfide, but with distinct structural differences shaped to fit the bulkier MSSM substrate, assigning Mtrs as uniquely functioning reductases. As MSH has been acknowledged as an attractive antitubercular target, the structural findings presented in this work may contribute towards future antituberculosis drug development.

Dietary Patterns and Fertility.

Diet has a key role in the reproductive axis both in males and females. This review aims to analyze the impacts of different dietary patterns on fertility. It appears that the Mediterranean diet has a predominantly protective role against infertility, while the Western diet seems to be a risk factor for infertility. Moreover, we focus attention also on dietary patterns in different countries of the World (Middle Eastern diet, Asian diet). In particular, when analyzing single nutrients, a diet rich in saturated fatty acids, cholesterol, animal proteins, and carbohydrates with high glycemic index is highly associated with male and female infertility. Finally, we evaluate the effects of vegetarian, vegan, and ketogenic diets on fertility, which seem to be still unclear. We believe that comprehension of the molecular mechanisms involved in infertility will lead to more effective and targeted treatments for infertile couples.

Protective Role of Lycopene in Subjects with Liver Disease: NUTRIHEP Study.

Liver diseases are constantly increasing throughout the world and are often associated with other diseases, but above all they are caused by improper diet. Adherence to a diet with abundant vegetables has now been widely demonstrated to be important in combating this pathological condition. The aim of this study was to explore the protective role of lycopene (LYC) extracts from cooked and fresh tomato. The study cohort included 969 participants assessed in the NUTRIHEP cohort (2005-2006) and the associated follow-up (2014-2016), divided into two groups, based on liver condition: NAFLD, or AFLD and FLD. The results indicated a statistical significance of LYC consumption, showing a protective role against liver disease, the best concentration being 9.50 mg/die, with an RR value of 0.59, p = 0.01, 0.39 to 0.90 at 95% C.I., and RRR = 0.40, p = 0.002, 0.22 to 0.71 at 95% C.I. The protective role of LYC extracts from tomato has not been amply demonstrated in humans. We conclude that this is one of the few papers in the literature to evaluate the protective effect of LYC against liver disease, as well as how this molecule could be used in future possible treatments. Utilizing lycopene as a supplement alone or in combination with other foods could be useful for developing treatments with reduced contraindications.

Ehrlich ascites carcinoma provokes renal toxicity and DNA injury in mice: Therapeutic impact of chitosan and maitake nanoparticles.

In this study, the impact of chitosan (CS) and maitake (GF) nanoparticles towards the renal toxicity induced by Ehrlich ascites carcinoma (EAC) in vivo model was conducted. Besides benchmark negative control group, EAC model was constructed by intraperitoneal injection (i.p.) of 2.5 × 106 cells. Alongside positive control, two groups of EAC-bearing mice received 100 mg/kg of CS and GF nanoparticles/body weight daily for 14 days. The kidney function was conducted by measuring urea, creatinine, ions, (anti)/oxidative parameters and DNA damage. Also, measuring immunoreactivity of P53, proliferating cell nuclear antigen (PCNA), and B-cell lymphoma 2 (Bcl-2) and apoptosis protein. The outcomes illustrated notable kidney toxicity, which indicated by elevations in urea, creatinine, oxidative stress, DNA damage and induction of apoptosis. These events were supported by the drastic alteration in kidney structure through histological examination. Administration of CS and GF nanoparticles was able to enhance the antioxidant power, which further reduced oxidative damage, DNA injury, and apoptosis. These results indicated the protective and therapeutic role of biogenic chitosan and maitake nanoparticles against nephrotoxicity.

Chaenomeles sinensis Extract Ameliorates Ovalbumin-Induced Allergic Rhinitis by Inhibiting the IL-33/ST2 Axis and Regulating Epithelial Cell Dysfunction.

Chaenomeles sinensis has traditionally been used as an herbal medicine due to its characteristics that protect against inflammation, hypertension, and mutagenesis. However, the effect of Chaenomeles sinensis extract (CSE) on allergic rhinitis (AR) and its underlying mechanisms have yet to be thoroughly investigated. The current study explored the likely effect of CSE on AR in an ovalbumin (OVA)-induced AR mouse model. To this end, OVA-specific immunoglobulins, nasal symptoms, cytokine production, the infiltration of inflammatory cells, and nasal histopathology were assessed to determine the role of CSE against AR. The supplementation of CSE was found to suppress OVA-specific IgE, while OVA-specific IgG2a was increased in the serum. Further, CSE ameliorated the production of T helper type 2 (Th2) cytokines whereas it increased Th1 cytokine levels in nasal lavage fluid. Moreover, the CSE treatment group exhibited significant inhibition of IL-33/ST2 signaling. Subsequently, CES reversed the OVA-induced enhancement of epithelial permeability and upregulated E-cadherin, thus indicating that CES plays a protective role on epithelial barrier integrity. Altogether, the oral administration of CSE effectively controlled allergic response by restricting the buildup of inflammatory cells, enhancing nasal and lung histopathological traits, and regulating cytokines associated with inflammation. Collectively, the results show that the supplementation of CSE at different doses effectively regulated AR, thus suggesting the therapeutic efficiency of CSE in suppressing airway diseases.

NcRNAs Orchestrate Chemosensitivity Induction by Neddylation Blockades.

We performed an integrative transcriptomic in silico analysis using lung adenocarcinoma A549 cells treated with the neddylation inhibitor MLN4924 and the gefitinib-resistant PC9 cell line (PC9GR). We focused on the transcriptional effects of the top differentially expressed ncRNA biotypes and their correlating stemness factors. Interestingly, MLN4924-treated cells showed a significant upregulation of mRNAs involved in carcinogenesis, cell attachment, and differentiation pathways, as well as a parallel downregulation of stemness maintenance and survival signaling pathways, an effect that was inversely observed in PC9GR cells. Moreover, we found that stemness factor expression could be contrasted by selected up-regulated ncRNAs upon MLN4924 treatment in a dose and time-independent manner. Furthermore, upregulated miRNAs and lncRNA-targeted mRNAs showed an evident enrichment of proliferation, differentiation, and apoptosis pathways, while downregulated ncRNA-targeted mRNAs were implicated in stem cell maintenance. Finally, our results proved that stemness (KLF4 and FGFR2) and epithelial-mesenchymal transition (ZEB2, TWIST2, SNAI2, CDH2, and VIM) factors, which are highly expressed in PC9GR cells compared to gefitinib-sensitive PC9 cells, could be abrogated with the neddylation inhibitor MLN4924 mainly through activation of epithelial differentiation pathways, thus exerting a protective role in lung cancer cells and chemosensitivity against lung tumorigenic transformation.

Integrated network pharmacology and experimental validation-based approach to reveal the underlying mechanisms and key material basis of Jinhua Qinggan granules against acute lung injury

Ethnopharmacological relevanceJinhua Qinggan granules (JHQG), the traditional Chinese formula come into the market in 2016, has been proved clinically effective against coronavirus disease. Acute lung injury (ALI) is a major complication of respiratory infection such as coronavirus and influenza virus, with a high clinical fatality rate. Macrophage activation-induced inflammatory response plays a crucial role in the pathogenesis of ALI. However, the participation of inflammatory response in the efficacy of JHQG and its material basis against ALI is still unknown. Aim of the studyThe research aims to investigate the inflammatory response-involved efficacy of JHQG on ALI, explore the “ingredient-target-pathway” mechanisms, and searching for key material basis of JHQG by integrated network pharmacology and experimental validation-based approach. Materials and methodsLipopolysaccharide (LPS)-induced ALI mice was established to assess the protective impact of JHQG. Network pharmacology was utilized to identify potential targets of JHQG and investigate its action mechanisms related to inflammatory response in treating ALI. The therapeutic effect and mechanism of the primary active ingredient in JHQG was verified through high performance liquid chromatography (HPLC) and a combination of wet experiments. ResultsJHQG remarkably alleviated lung damage in mice model via suppressing macrophage activation, and inhibiting pro-inflammatory mediator level, p-ERK and p-STAT3 expression, TLR4/NF-κB activation. Network pharmacology combined with HPLC found luteolin is the main effective component of JHQG, and it could interact with TLR4/MD2 complex, further exerting the anti-inflammatory property and the protective role against ALI. ConclusionsIn summary, our finding clarified the underlying mechanisms and material basis of JHQG therapy for ALI by integrated network pharmacology and experimental validation-based strategy.

The protective role of condensed tannins on growth inhibition and enterohepatic injury induced by histamine in Chinese seabass (Lateolabrax maculatus)

Histamine has been documented to induce growth inhibition and tissue injury in animals, whereas information regarding the toxicity of histamine and the detoxication of condensed tannins (CT) in Chinese seabass (Lateolabrax maculatus) is rare. In this study, three diets were prepared to contain 0 g/kg of histamine (G1), 0.1 g/kg of histamine (G2), and 0.1 g/kg of histamine plus 1 g/kg of CT (G3). Fish were randomly divided into 12 tanks with 40 fish per tank and 4 tanks per diet. The results showed that the final body weight, weight gain rate, specific growth rate, total antioxidant capacity, and the activities of trypsin, lipase, catalase, superoxide dismutase and lysozyme were lower (P < 0.05) but the serum concentration of aspartate and alanine aminotransferases and glucose were higher (P < 0.05) in G2 than in G1 and G3. These parameters were similar (P > 0.05) between G1 and G3. The FCR was ranked as G2 > G3 > G1 (P < 0.05). Compared with G1 and G3, the deformation and atrophy of the intestinal villus and the vacuolation of hepatocytes were intensified in G2. In conclusion, 0.1 g/kg of histamine inhibited digestion, induced intestinal and liver injury, decreased antioxidant and immune capacity and reduced growth performance of L. maculatus. Supplementation of 1 g/kg of CT in the Lateolabrax maculatus diet alleviated histamine-induced toxicity owing to the protective effect of CT against oxidative damage.