Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. METHODS: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. RESULTS: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. CONCLUSION: LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.

A chromosome-level genome assembly of Chinese quince (Pseudocydonia sinensis).

Introduction: Pseudocydonia sinensis, also known as Chinese quince, is a perennial shrub or small tree highly valued for its edibility and medicinal properties. Method: This study presents the first chromosome-level genome assembly of P. sinensis, achieved using HiFi sequencing and Hi-C scaffolding technology. Results: The assembly resulted in a high-quality genome of 576.39 Mb in size. The genome was anchored to 17 pseudo-chromosomes, with a contig N50 of 27.6 Mb and a scaffold N50 of 33.8 Mb. Comprehensive assessment using BUSCO, CEGMA and BWA tools indicates the high completeness and accuracy of the genome assembly. Our analysis identified 116 species-specific genes, 1196 expanded genes and 1109 contracted genes. Additionally, the distribution of 4DTv values suggests that the most recent duplication event occurred before the divergence of P. sinensis from both Chaenomeles pinnatifida and Pyrus pyrifolia. Discussion: The assembly of this high-quality genome provides a valuable platform for the genetic breeding and cultivation of P. sinensis, as well as for the comparison of the genetic complexity of P. sinensis with other important crops in the Rosaceae family.

Post-marketing safety concerns with elagolix: a disproportionality analysis of the FDA adverse event reporting system.

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown. METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed from January 2019 to June 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs). RESULTS: After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important AEs that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

Disulfidptosis and ferroptosis related genes predict prognosis and personalize treatment for hepatocellular carcinoma.

Background: Understanding the interplay between disulfidptosis, ferroptosis, and hepatocellular carcinoma (HCC) could provide valuable insights into the pathogenesis of HCC and potentially identify novel therapeutic targets for the treatment of this deadly disease. This study aimed to identify a prognostic signature for HCC by examining the differential expression of genes related to disulfidptosis and ferroptosis (DRG-FRG), and to assess its clinical applicability. Methods: By integrating 23 disulfidptosis and 259 ferroptosis related genes with HCC messenger RNA (mRNA) expression data from The Cancer Genome Atlas (TCGA), differentially expressed DRG-FRG genes were identified. From these, 11 DRG-FRG genes were selected to construct a risk signature model using least absolute shrinkage and selection operator regression analyses. The prognostic performance of this model was evaluated by Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) analysis. Subsequently, a nomogram was built by combining the signature with clinical variables. To further delve into the underlying mechanisms, we performed bioinformatics analysis using a variety of databases. Results: A prognostic signature based on 11 DRG-FRG genes effectively categorized HCC patients into high- and low-risk groups, showing a significant survival difference. Even after considering clinical variables, this signature remained an independent prognostic factor. Furthermore, the signature played a role in various critical biological processes and pathways that drive HCC progression. Potential therapeutic benefits could be derived from small molecule drugs targeting NQO1 and SLC7A11. Interestingly, the high-risk group exhibited resistance to several chemotherapeutic drugs, yet showed sensitivity to others when contrasted with the low-risk group. Lastly, the DRG-FRG genes signature had a strong correlation with the tumor immune microenvironment, marked by an elevated expression of immune checkpoint molecules in the high-risk group. Conclusions: The signature based on 11 DRG-FRG genes stands out as a promising prognostic biomarker for HCC. Beyond its predictive value, it sheds light on the intricate crosstalk between DRG-FRG genes and HCC. Importantly, these findings could pave the way for enhanced prognostic prediction, informed treatment decisions, and the advancement of immunotherapy for HCC patients.

Structural and compositional diversity of biosurfactants produced by a novel strain of Sporosarcina luteola ME44 from oil reservoir.

The urealytically active microorganism Sporosarcina luteola induces the precipitation of metals, which has attracted attention in biomineralization, bioremediation, and industrial waste recycling. Herein, we report a novel biosurfactant-producing strain of S. luteola ME44 isolated from Chinese Oilfield. The structure, composition, and surface activity of the biosurfactants produced by S. luteola ME44 were investigated by using a combination of the high-performance liquid chromatography, time-of-flight mass spectrometry, and surface tensiometer. The biosurfactant extracted by strain ME44 was identified as surfactin with five variants and the yield was 1010 ± 60 mg⋅L-1 . This is the first report on the structural composition and surface activity of biosurfactants isolated from the S. luteola. It extended our knowledge about the role of the species S. luteola in the ecosystem of extreme natural environments such as oil reservoir. In addition, S. luteola ME44 showed bioprecipitation properties for metal ions Cd(II), Cu(II), Zn(II), and Ag(I), which indicated the application potential of S. luteola in the field of bioremediation.

Retinal safety and toxicity study of artesunate in vitro and in vivo.

Background: Artesunate (ART), a member of the artemisinin family, possesses multi-properties, including anti-inflammation, anti-oxidation, and anti-tumor. ART was recently reported to show anti-neovascularization effect on the cornea, iris, and retina. Compared to the expensive anti-VEGF treatment, this versatile, economical treatment option is attractive in the ophthalmic field. The safety and toxicity profile of ART intravitreal application are in utmost need. Methods: In this study, immortalized microglial (IMG) cells were treated with ART to determine the safe concentrations without inducing overt inflammatory reactions. Reverse transcription-polymerase chain reaction analysis was used to detect the cytokine expressions in IMG cells in response to ART stimulation. Various doses of ART were intravitreally injected into the right eyes of C57BL/6 mice. Retinal function was tested by electroretinogram, and retinal ganglion cell (RGC) survival was evaluated by counting Brn3a stained cells in flat-mounted retinas at 7 days after ART injection. Results: ART below 5µM was safe for IMG cells in vitro. Both 2.5 and 5 â€‹µM ART treatment increased IL-10 gene expression in IMG cells while not changing IL-1ß, IL-6, TNF-α, and Arg-1. In the in vivo study, intravitreal injection of ART below 100 â€‹µM did not cause deterioration in the retinal function and RGC survival of the mouse eyes, while 1 â€‹mM ART treatment significantly attenuated both the scotopic and photopic b-wave amplitudes and impaired RGC survival. In addition, treatment with ART of 25, 50, and 100 â€‹µM significantly decreased TNF-α gene expression while ART of 100 â€‹µM significantly increased IL-10 in the mouse retina. Conclusions: Intravitreal injection of 100 â€‹µM ART could downregulate TNF-α while upregulate IL-10 in the mouse retina without causing retinal functional deterioration and RGC loss. ART might be used as anti-inflammatory agent for retinal disorders.

The polarization of M2 macrophages can be adjusted to alleviate renal injury by methylprednisolone in sepsis-AKI.

Acute kidney injury in sepsis patients has an extreme mortality rate in clinical. It obviously seems that immune cells, for example, macrophages are involved with this process. Macrophages, as highly important immune cells, play a significant role in the development of human kidney diseases. But the specific role of macrophages in this process is still unclear. Under different timeline points, we surprisingly found that macrophages had the most dynamic changes in acute kidney injury immune cells. Based on macrophages' functions, they are primarily classified into M1 macrophages (pro-inflammatory) and M2 macrophages (anti-inflammatory). The polarization of M2 macrophages is closely associated with the seriousness of sepsis-induced kidney injury, but how to modulate their polarization to alleviate sepsis-associated renal damage remains unknown. We discovered that the polarization of M2 macrophages after methylprednisolone injection can significantly alleviate acute kidney injury by reducing secreted cytokine. This study suggests that the proportion of macrophage subtypes can be regulated by methylprednisolone to alleviate acute kidney injury in sepsis to provide a new sight for a clinical to provide a promising strategy for renal injury caused.

Effects of Friction Stir Welding on the Mechanical Behaviors of Extrusion-Based Additive Manufactured Polymer Parts.

The friction stir welding (FSW) of thermoplastic polymers is gradually receiving attention because of its advantages including high efficiency and pollution-free manufacturing. The extrusion-based additive manufacturing (EAM) of polymers has also become one of the main processing methods for thermoplastic parts. In this paper, a hybrid manufacturing method for the FSW process and EAM technology is proposed and explored. The effects of the FSW process using two different welding tools on the mechanical behaviors of 3D printing polymer parts were compared and investigated and the corresponding mechanism was analyzed. The results show that the appropriate welding tool is beneficial for eliminating the anisotropy and decreasing the porosity of 3D-printed parts. Therefore, the improving effects of the FSW process on the mechanical behaviors of the EAM parts are verified. The mechanism was attributed to the high-speed rotation of the welding tool with the appropriate shape, which can promote the flow of polymer melt in the welding region, leading to the formation of dense structures caused by the entanglement of the molecular chains. This study may provide some assistance in modern industrial manufacturing for the processing of large custom components.

A new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from an oil field in China.

The genus Fictibacillus contains twelve species significant in the synthesis of cellulose-degrading enzymes and phenylalanine dehydrogenase, isolated mainly from marine sedimentary environments. Here, we report a new biosurfactant-producing strain, Fictibacillus nanhaiensis ME46, isolated from Daqing oil field in China. The biosurfactant extracted from Strain ME46 was determined as surfactin, one of the representative families of lipopeptide biosurfactants. The yield of the surfactin produced by strain ME46 was 0.62 g·L-1 as determined by high-performance liquid chromatography, and the critical micelle concentration (CMC) of the surfactin was estimated to be about 68 mg·L-1 and the surface tension at CMC was 35.1 mN·m-1. This study extended our knowledge about the role of the species Fictibacillus nanhaiensis in the ecosystem of natural environments such as the oil field.

Quantitative determination of rhamnolipid using HPLC-UV through carboxyl labeling.

Rhamnolipid, as a low-toxic, biodegradable and environmentally friendly biosurfactant, has broad application prospects in many industries. However, the quantitative determination of rhamnolipid is still a challenging task. Here, a new sensitive method for the quantitative analysis of rhamnolipid based on a simple derivatization reaction was developed. In this study, 3-[3'-(l-rhamnopyranosyloxy) decanoyloxy] decanoic acid (Rha-C10-C10) and 3-[3'-(2'-O-α-l-rhamnopyranosyloxy) decanoyloxy] decanoic acid (Rha-Rha-C10-C10) were utilized as the representative rhamnolipids. Liquid chromatography-mass spectrometry and high-performance liquid chromatography-ultra violet results showed that these two compounds were successfully labeled with 1 N1-(4-nitrophenyl)-1,2-ethylenediamine. There was an excellent linear relationship between rhamnolipid concentration and peak area of labeled rhamnolipid. The detection limits of the Rha-C10-C10 and Rha-Rha-C10-C10 were 0.018 mg/L (36 nmol/L) and 0.014 mg/L (22 nmol/L), respectively. The established amidation method was suitable for the accurate analysis of rhamnolipids in the biotechnological process. The method had good reproducibility with the relative standard deviation of 0.96% and 0.79%, respectively, and sufficient accuracy with a recovery of 96%-100%. This method was applied to quantitative analysis of 10 rhamnolipid homologs metabolized by Pseudomonas aeruginosa LJ-8. The single labeling method was used for the quantitative analysis of multiple components, which provided an effective method for the quality evaluation of other glycolipids with carboxyl groups.

Structural Diversity of the Lipopeptide Biosurfactant Produced by a Newly Isolated Strain, Geobacillus thermodenitrifcans ME63.

The genus Geobacillus is active in degradation of hydrocarbons in thermophilic and facultative environments since it was first reported in 1920. Here, we report a new strain, Geobacillus thermodenitrificans ME63, isolated from an oilfield with the ability of producing the biosurfactant. The composition, chemical structure, and surface activity of the biosurfactant produced by G. thermodenitrificans ME63 were investigated by using a combination of the high-performance liquid chromatography, time-of-flight ion mass spectrometry, and surface tensiometer. The biosurfactant produced by strain ME63 was identified as surfactin with six variants, which is one of the representative family of lipopeptide biosurfactants. The amino acid residue sequence in the peptide of this surfactin is N-Glu → Leu → Leu → Val → Leu → Asp → Leu-C. The critical micelle concentration (CMC) of the surfactin is 55 mg L-1, and the surface tension at CMC is 35.9 mN m-1, which is promising in bioremediation and oil recovery industries. The surface activity and emulsification properties of biosurfactants produced by G. thermodenitrificans ME63 showed excellent resistance to temperature changes, salinity changes, and pH changes.

Neuroprotection of Emodin by Inhibition of Microglial NLRP3 Inflammasome-Mediated Pyroptosis.

BACKGROUND: Neuroinflammation triggered by chronic cerebral ischemia-induced microglial pyroptosis is a significant contributor to vascular cognitive impairment. It has been shown that emodin possesses anti-inflammatory and neuroprotective properties, however, it's potential molecular and signaling transduction pathway remains to be illuminated. This study researched the neuroprotective mechanisms of emodin focussing on emodin effects on lipopolysaccharide/adenosine triphosphate (LPS/ATP)-caused pyroptosis in BV2 cells and HT-22 hippocampal neurons. METHODS: To explore the neuroprotective effect of emodin, Emodin was applied to BV2 cells, HT-22 hippocampal neurons, and BV2/HT-22 co-cultures stimulated with LPS/ATP to evaluate the cell morphology, levels of inflammatory factors, NLRP3 inflammatory inflammasome activity and focal pyroptosis-related protein expression, as same as neuronal apoptosis. RESULTS: Emodin alleviated LPS/ATP-induced pyroptosis of BV2 cells by preventing the activity of the NLRP3 inflammasome and the cleavage of pyroptosis executive protein Gasdermin D (GSDMD). Furthermore, levels of interleukin (IL)-18, IL-1ß and tumor necrosis factor (TNF)-α were reduced, the apoptosis of HT-22 hippocampal neurons was attenuated, and cell viability was restored. CONCLUSIONS: Emodin can antagonize microglial neurotoxicity by inhibiting microglial pyroptosis, thereby exerting anti-inflammatory and neuroprotective effects.

Genetic engineering of the branched-chain fatty acid biosynthesis pathway to enhance surfactin production from Bacillus subtilis.

Surfactin, which is composed of a ß-hydroxy fatty acid chain and a peptide ring, has drawn considerable attention due to its potential applications in the biomedicine, bioremediation, and petroleum industries. However, the low yield of surfactin from wild strains still restricts its industrial applications. In this study, eight genes relevant to the fatty acid biosynthesis pathway were targeted to enhance surfactin production, and high surfactin-yielding strains with potential industrial applications were obtained. When ldeHA and acc were co-overexpressed, the surfactin yield of recombinant strains TDS8 and TPS8 increased to 1.55- and 1.19-fold of their parental strains, respectively, again proving that the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA is the rate-limiting step in fatty acid biosynthesis. Furthermore, changes in surfactin isoforms of recombinant strain TPS8 suggest that the fatty acid precursor synthesis pathway can be modified to improve the proportion of different isoforms. In addition, the deletion of lpdV, which is responsible for the conversion of α-ketoacyl-CoA precursors, resulted in a sharp decrease in surfactin production, further demonstrating the importance of branched-chain fatty acid biosynthesis in surfactin production. This work will facilitate the design and construction of more efficiently engineered strains for surfactin production and further extend industrial applications.

Extracellular vesicles for ischemia/reperfusion injury-induced acute kidney injury: a systematic review and meta-analysis of data from animal models.

BACKGROUND: Acute kidney injury (AKI) induced by ischemia/reperfusion injury significantly contribute to the burden of end-stage renal disease. Extracellular vesicles (EVs), especially for stem/progenitor cell-derived EVs (stem/progenitor cell-EVs), have emerged as a promising therapy for ischemia/reperfusion injury-induced AKI. However, their regulatory effects remain poorly understood, and their therapeutic efficiency in clinical trials is controversial. Here, we performed this systematic review and meta-analysis to assess the stem/progenitor cell-EV efficacy in treating ischemia/reperfusion injury-induced AKI in preclinical rodent models. METHODS: A literature search was performed in PubMed, Embase, Scopus, and Web of Science to identify controlled studies about the therapeutic efficiency of stem/progenitor cell-EVs on ischemia/reperfusion injury-induced AKI rodent models. The level of SCr, an indicator of renal function, was regarded as the primary outcome. Meta-regression analysis was used to reveal the influential factors of EV therapy. Sensitivity analysis, cumulative meta-analysis, and assessment of publication bias were also performed in our systematic review and meta-analysis. A standardized mean difference (SMD) was used as the common effect size between stem/progenitor cell-EV-treated and control groups, with values of 0.2, 0.5, 0.8, and 1.0 defined as small, medium, large, and very large effect sizes, respectively. RESULTS: A total of 30 studies with 985 ischemia/reperfusion injury-induced AKI rodent models were included. The pooled results showed that EV injection could lead to a remarkable sCr reduction compared with the control group (SMD, - 3.47; 95%CI, - 4.15 to - 2.80; P < 0.001). Meanwhile, the EV treatment group had lower levels of BUN (SMD, - 3.60; 95%CI, - 4.25 to - 2.94; P < 0.001), indexes for tubular and endothelial injury, renal fibrosis (fibrosis score and α-SMA), renal inflammation (TNF-α, IL-1ß, iNOS, and CD68 + macrophages), but higher levels of indexes for tubular proliferation, angiogenesis-related VEGF, and reactive oxygen species. However, our meta-regression analysis did not identify significant associations between sCr level and cell origins of EVs, injection doses, delivery routes, and therapy and outcome measurement time (all P values > 0.05). Significant publication bias was observed (Egger's test, P < 0.001). CONCLUSION: Stem/progenitor cell-EVs are effective in improving renal function in rodent ischemia/reperfusion injury-induced AKI model. These vesicles may help (i) reduce cell apoptosis and stimulate cell proliferation, (ii) ameliorate inflammatory injury and renal fibrosis, (iii) promote angiogenesis, and (iv) inhibit oxidative stress. However, the current systematic review and meta-analysis did not identify significant influential factors associated with treatment effects. More preclinical studies and thoughtfully designed animal studies are needed in the future.

Discovery of the non-cosmopolitan lineages in Candidatus Thermoprofundales.

The recently proposed order Candidatus Thermoprofundales, currently containing only one family-level lineage Marine Benthic Group-D (MBG-D), is distributed in global subsurface ecosystems and ecologically important, but its diversity, evolution and metabolism remain largely unknown. Here we described two novel family-level specialized lineages in Ca. Thermoprofundales, JdFR-43 and HyVt, which are restricted to specific biotopes (primarily in marine hydrothermal vents and occasionally in oil reservoirs and hot springs) in contrast to the cosmopolitan lineage MBG-D. The comparative genomics revealed that the specialized lineages have streamlined genomes, higher GC contents, enriched genes associated with nucleotide biosynthesis, ribosome biogenesis and DNA repair and additional thermostable aminopeptidases, enabling them to adapt to high-temperature habitats such as marine hydrothermal vents, deep subsurface oil reservoirs and hot springs. On the contrary, the unique metabolic traits of the cosmopolitan MBG-D, motility, glycolysis, butanoate metabolism, secondary metabolites production and additional genes for specific peptides and carbohydrates degradation potentially enhance its response to environmental change. Substrate preference is found for most MAGs across all lineages with the ability to utilize both polysaccharides (chitin and starch) and proteinaceous substances, whereas JdFR-43 members from oil reservoirs can only utilize proteins. These results expand the diversity of Ca. Thermoprofundales significantly and further improve our understandings of the adaptations of Ca. Thermoprofundales to various environments.

[Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease].

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

The mitochondrial ß-oxidation enzyme HADHA restrains hepatic glucagon response by promoting ß-hydroxybutyrate production.

Disordered hepatic glucagon response contributes to hyperglycemia in diabetes. The regulators involved in glucagon response are less understood. This work aims to investigate the roles of mitochondrial ß-oxidation enzyme HADHA and its downstream ketone bodies in hepatic glucagon response. Here we show that glucagon challenge impairs expression of HADHA. Liver-specific HADHA overexpression reversed hepatic gluconeogenesis in mice, while HADHA knockdown augmented glucagon response. Stable isotope tracing shows that HADHA promotes ketone body production via ß-oxidation. The ketone body ß-hydroxybutyrate (BHB) but not acetoacetate suppresses gluconeogenesis by selectively inhibiting HDAC7 activity via interaction with Glu543 site to facilitate FOXO1 nuclear exclusion. In HFD-fed mice, HADHA overexpression improved metabolic disorders, and these effects are abrogated by knockdown of BHB-producing enzyme. In conclusion, BHB is responsible for the inhibitory effect of HADHA on hepatic glucagon response, suggesting that HADHA activation or BHB elevation by pharmacological intervention hold promise in treating diabetes.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-ß-induced inflammatory reactions in microglial cells.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

Septoplasty alone is not suitable for most structural nasal obstructions.

Septoplasty is widely used in the treatment of structural nasal obstructions, and it also has a good effect and a high degree of postoperative satisfaction. However, there a large number of structures demonstrate abnormalities related to structural nasal obstruction, including the external nose, maxilla, nasal cavity and paranasal sinus. Nasal septum deviation is only one signs of structural nasal obstruction and does not represent all possible structural abnormalities of the nasal cavity and its surrounding structure. Septoplasty is only performed to correct deviations of the nasal septum, which in many cases is obviously insufficient in restoring the symmetry of the nasal structure. Therefore, septoplasty alone is not suitable for the treatment of most structural nasal obstructions. Nasal ventilation expansion surgery, which typically covers more abnormal structural correction procedures than septoplasty, should be used when describing the treatment of structural nasal obstruction.

Vertical transmission of hepatitis B virus: propositions and future directions.

ABSTRACT: Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.