Comparative efficacy of commercial oral poly-herbal traditional Chinese medicine formulations combined with western medicine in benign prostatic hyperplasia management: a systematic review and network meta-analysis.

Background: Benign prostatic hyperplasia (BPH) is prevalent among the aging male population and often presents with distressing lower urinary tract symptoms. There is emerging evidence that commercial oral poly-herbal traditional Chinese medicine (TCM) formulation combined with Western medicine (WM) may offer enhanced therapeutic effects compared to WM alone in BPH treatment. Nevertheless, determining the optimal formulations for BPH remains controversial. We aimed to employ a network meta-analysis to compare and assess differences among commonly used and recommended poly-herbal TCM formulations outlined in the Chinese guidelines for BPH treatment, providing clinical medication recommendations and guidance. Methods: We extensively searched for RCTs of BPH patients that had oral poly-herbal TCM formulations and WM treatment, covering both English and Chinese databases up to 31 October 2023. The quality of the included studies was evaluated using the Cochrane risk-of-bias tool Version 2 (ROB2). A Bayesian network meta-analysis was performed to assess the effectiveness of various formulations, followed by sensitivity and subgroup analyses. Results: Our meta-analysis included 107 RCTs involving 11,037 patients across 16 oral poly-herbal TCM formulations. The quality of the selected studies was assessed as "Some concerns". Most formulations combined with WM demonstrated superior therapeutic efficacy compared to WM alone. For clinical effective rate, Jingui Shenqi pill (JGSQ) + WM had the highest-ranking probability (87.38%). Concerning International Prostate Symptom Score (IPSS) and maximum flow rate of urine, Guizhi Fuling capsule (GZFL) + WM was most effective (91.10% and 98.55%). Regarding the quality of life score and postvoid residual urine, Pulean tablet (PLA) + WM ranked first (86.71% and 91.81%). In controlling prostate volume, Huange capsule (HE) + WM demonstrated the highest efficacy (95.65%). Additionally, among the interventions, Lingze (LZ) + WM capsule exhibited the lowest incidence of adverse drug reactions (2.32%). Conclusion: Combining oral poly-herbal TCM formulations with WM may provide greater therapeutic benefits in BPH treatment compared to WM alone. JGSQ, GZFL, PLA, and HE emerged as promising treatment options. However, further rigorous empirical studies are essential to substantiate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459651, CRD 42023459651.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Mitochondrial quality control in human health and disease.

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.

Development and validation of an artificial intelligence-based model for detecting urothelial carcinoma using urine cytology images: a multicentre, diagnostic study with prospective validation.

Background: Urine cytology is an important non-invasive examination for urothelial carcinoma (UC) diagnosis and follow-up. We aimed to explore whether artificial intelligence (AI) can enhance the sensitivity of urine cytology and help avoid unnecessary endoscopy. Methods: In this multicentre diagnostic study, consecutive patients who underwent liquid-based urine cytology examinations at four hospitals in China were included for model development and validation. Patients who declined surgery and lacked associated histopathology results, those diagnosed with rare subtype tumours of the urinary tract, or had low-quality images were excluded from the study. All liquid-based cytology slides were scanned into whole-slide images (WSIs) at 40 × magnification and the WSI-labels were derived from the corresponding histopathology results. The Precision Urine Cytology AI Solution (PUCAS) was composed of three distinct stages (patch extraction, features extraction, and classification diagnosis) and was trained to identify important WSI features associated with UC diagnosis. The diagnostic sensitivity was mainly used to validate the performance of PUCAS in retrospective and prospective validation cohorts. This study is registered with the ChiCTR, ChiCTR2300073192. Findings: Between January 1, 2018 and October 31, 2022, 2641 patients were retrospectively recruited in the training cohort, and 2335 in retrospective validation cohorts; 400 eligible patients were enrolled in the prospective validation cohort between July 7, 2023 and September 15, 2023. The sensitivity of PUCAS ranged from 0.922 (95% CI: 0.811-0.978) to 1.000 (0.782-1.000) in retrospective validation cohorts, and was 0.896 (0.837-0.939) in prospective validation cohort. The PUCAS model also exhibited a good performance in detecting malignancy within atypical urothelial cells cases, with a sensitivity of over 0.84. In the recurrence detection scenario, PUCAS could reduce 57.5% of endoscopy use with a negative predictive value of 96.4%. Interpretation: PUCAS may help to improve the sensitivity of urine cytology, reduce misdiagnoses of UC, avoid unnecessary endoscopy, and reduce the clinical burden in resource-limited areas. The further validation in other countries is needed. Funding: National Natural Science Foundation of China; Key Program of the National Natural Science Foundation of China; the National Science Foundation for Distinguished Young Scholars; the Science and Technology Planning Project of Guangdong Province; the National Key Research and Development Programme of China; Guangdong Provincial Clinical Research Centre for Urological Diseases.

pH-Modulated 1D Hierarchical Self-Assembly of a Brush-Like Poly-Para-Phenylene Homopolymer.

The controllable self-assembly of conjugated homopolymers, especially homopolymers without other segments (a prerequisite for phase separation), which can afford chances to achieve tunable optical/electronic properties, remains a great challenge due to their poor solubility and has remained rarely documented. Herein, a conjugated homopolymer (DPPP-COOH) is synthesized, which has a unique brush-like structure with a conjugated dendritic poly-para-phenylene (DPPP) backbone and alkyl-carboxyl side chains at both edges of the backbone. The introduction of carboxyl makes the brush-like homopolymer exhibit pH-modulated 1D hierarchical self-assembly behavior in dilute solution, and allows for flexible morphological regulation of the assemblies, forming some uncommon superstructures including ultralong nanowires (at pH 7), superhelices (at pH 10) and "single-wall" nanotubes (at pH 13), respectively. Furthermore, the good aqueous dispersibility and 1D feature endow the superstructures formed in a high-concentration neutral solution with high broad-spectrum antibacterial performance superior to that of many conventional 1D materials.

Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex.

Under stress conditions, translationally stalled mRNA and associated proteins undergo liquid-liquid phase separation and condense into cytoplasmic foci called stress granules (SGs). Many viruses hijack SGs for their pathogenesis; however, whether pathogenic bacteria also exploit this pathway remains unknown. Here, we report that members of the OspC family of Shigella flexneri induce SG formation in infected cells. Mechanistically, the OspC effectors target multiple subunits of the host translation initiation factor 3 complex by ADP-riboxanation. The modification of eIF3 leads to translational arrest and thus the formation of SGs. Furthermore, OspC-mediated SGs are beneficial for S. flexneri replication within infected host cells, and bacterial strains unable to induce SGs are attenuated for virulence in a murine model of infection. Our findings reveal a mechanism by which bacterial pathogens induce SG assembly by inactivating host translational machinery and promote bacterial proliferation in host cells.

Comprehensive analysis of m6A modification in lipopolysaccharide-induced acute lung injury in mice.

BACKGROUND: N6-Methyladenosine (m6A) methylation is the most prevalent post-transcriptional modification in mRNA, and plays significant roles in various diseases. Nevertheless, the precise functions of m6A modification in the formation of ALI remain unclear. In this study we explore the transcriptome distribution of m6A methylation and its probable roles of in ALI. METHODS: Lipopolysaccharide (LPS) was utilized to establish an ALI mouse model. Real-time qPCR, Western blotting and m6A dot blot were utilized to assess m6A methylation level and the expression of m6A methylation enzymes. MeRIP-Seq and RNA-seq were utilized to explore differential m6A modifications and differentially expressed genes in ALI mice. The hub genes and enriched pathways were assessed by Real-time qPCR and Western blotting. RESULTS: Our findings showed that overall m6A methylation level was increased in ALI mice lung tissues, accompanied by lower levels of METTL3 and FTO. Notably, the protein expression of these methylases were different in various cells. There were 772 differently expressed m6A peaks in ALI as compared to the control group, with 316 being hypermethylated and 456 being hypomethylated. GO and KEGG analyses demonstrated these differentially methylated genes were associated with the calcium signaling pathway and cAMP signaling pathway. Furthermore, we identified 50 genes with distinct m6A peaks and mRNA expressions by combined analysis of MeRIP-Seq and RNA-Seq. KEGG analysis also demonstrated that these overlapped genes were closely associated with the calcium signaling pathway, cGMP-PKG signaling pathway, etc. Besides, Western blotting results demonstrated that the protein expression of Fibronectin leucine-rich transmembrane protein 3 (Flrt3) as well as the calcium signaling pathway and cGMP-PKG signaling pathway, increased significantly after ALI. CONCLUSIONS: m6A modification was paramount in the pathogenesis of ALI, and provided a foundation for the further investigation in the prevention and treatment of ALI.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1.

Abnormal activation of the oncogene YAP in the Hippo pathway is a major feature in liver cancer and inactivation of MST1/2 has been shown to be responsible for the overactivation of YAP that led to tumorigenesis. However, mechanisms underlying MST1/2 dysregulation remain poorly understood. RNA-seq analysis and genome (KEGG) pathway enrichment analysis were used to identify genes and pathways that were regulated by SIRT7. qRT-PCR, ChIP, and luciferase assay were used to investigate transcriptional regulation. Mass spectrometry, co-immunoprecipitation and immunoprecipitation were used to exam protein-protein interaction and post-transcriptional modification. A xenograft mouse model was used to confirm the effect of SIRT7 and SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation in vivo. We found that SIRT7 suppresses MST1 by both transcriptional regulation and post-transcriptional modification, which in turn promotes YAP nuclear localization and transcriptional activation in liver cancer. Mechanistically, we revealed that SIRT7 suppresses MST1 transcription by binding to the MST1 promoter and inducing H3K18 deacetylation in its promoter region. In addition, SIRT7 directly binds to and deacetylates MST1, which primes acetylation-dependent MST1 ubiquitination and protein degradation. In clinical samples, we confirmed a negative correlation between SIRT7 and MST1 protein levels, and high SIRT7 expression correlated with elevated YAP expression and nuclear localization. In addition, SIRT7 specific inhibitor 2800Z sufficiently inhibited HCC growth by disrupting the SIRT7/MST1/YAP axis. Our data thus revealed the previously undescribed function of SIRT7 in regulating the Hippo pathway in HCC and further proved that targeting SIRT7 might provide novel therapeutic options for the treatment of liver cancer.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing.

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

Molecular Mechanism of Qingzaojiufei Decoction in the Treatment of Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking.

BACKGROUND: In recent years, pulmonary fibrosis (PF) has increased in incidence and prevalence. Qingzaojiufei decoction (QD) is a herbal formula that is used for the treatment of PF. OBJECTIVE: In this research, network pharmacology and molecular docking methods were used to explore the major chemical components and potential mechanisms of QD in the treatment of PF. METHODS: The principal components and corresponding protein targets of QD were used to screen on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and high-throughput experiment-and reference-guided database (HERB), Cytoscape 3.7.2 was used to construct the drug-component-target network. PF targets were collected by GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The protein-protein interaction (PPI) network was constructed by importing compound-disease intersection targets into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape3.7.2. We further performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the intersecting targets. In the last, we validated the core targets and active compounds by molecular docking. RESULTS: The key compounds of quercetin, (-)-epigallocatechin-3-gallate, and kaempferol of QD were obtained. The key targets of AKT1, TNF, and IL6 of QD were obtained. The molecular docking results show that quercetin, (-)-epigallocatechin-3-gallate and kaempferol work well with AKT1, TNF and IL6. CONCLUSION: This research shows the multiple active components and molecular mechanism of QD in the treatment of PF and offers resources and suggestions for future studies.

Incorrect Electrocardiogram Lead Placement in ST-Segment-Elevation Myocardial Infarction.

This case report describes a patient in their 70s with acute onset waxing and waning chest pressure, which radiated to both arms and was accompanied by shortness of breath.

Pretreatment with Kahweol Attenuates Sepsis-Induced Acute Lung Injury via Improving Mitochondrial Homeostasis in a CaMKKII/AMPK-Dependent Pathway.

SCOPE: It is well-established that dysregulated mitochondrial homeostasis in macrophages leads to inflammation, oxidative stress, and tissue damage, which are essential in the pathogenesis of sepsis-induced acute lung injury (ALI). Kahweol, a natural diterpene extracted from coffee beans, reportedly possesses anti-inflammatory and mitochondrial protective properties. Herein, the study investigates whether Kahweol can alleviate sepsis-induced ALI and explore the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are intraperitoneally injected with lipopolysaccharide (LPS) for 12 h to induce ALI. Pretreatment with kahweol by gavage for 5 days significantly alleviates lung pathological injury, inflammation, and oxidative stress, accompanied by shifting the dynamic process of mitochondria from fission to fusion, enhancing mitophagy, and activating AMPK. To investigate the underlying molecular mechanisms, differentiated THP-1 cells are cultured in a medium containing Kahweol for 12 h prior to LPS exposure, yielding consistent findings with the in vivo results. Moreover, AMPK inhibitors abrogate the above effects, indicating Kahweol acts in an AMPK-dependent manner. Furthermore, the study explores how Kahweol activates AMPK and finds that this process is mediated by CamKK II. CONCLUSION: Pretreatment with Kahweol attenuates sepsis-induced acute lung injury via improving mitochondrial homeostasis in a CaMKKII/AMPK-dependent pathway and may be a potential candidate to prevent sepsis-induced ALI.

HDAC3 promotes macrophage pyroptosis via regulating histone deacetylation in acute lung injury.

Activated inflammation and pyroptosis in macrophage are closely associated with acute lung injury (ALI). Histone deacetylase 3 (HDAC3) serves as an important enzyme that could repress gene expression by mediating chromatin remodeling. In this study, we found that HDAC3 was highly expressed in lung tissues of lipopolysaccharide (LPS)-treated mice. Lung tissues from macrophage HDAC3-deficient mice stimulated with LPS showed alleviative lung pathological injury and inflammatory response. HDAC3 silencing significantly blocked the activation of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway in LPS-induced macrophage. LPS could recruit HDAC3 and H3K9Ac to the miR-4767 gene promoter, which repressed the expression of miR-4767 to promote the expression of cGAS. Taken together, our findings demonstrated that HDAC3 played a pivotal role in mediating pyroptosis in macrophage and ALI by activating cGAS/STING pathway through its histone deacetylation function. Targeting HDAC3 in macrophage may provide a new therapeutic target for the prevention of LPS-induced ALI.

Synergistic Effect of Electron Scattering and Space Charge Transfer Enabled Unprecedented Room Temperature NO2 Sensing Response of SnO2.

Metal oxide gas sensors have long faced the challenge of low response and poor selectivity, especially at room temperature (RT). Herein, a synergistic effect of electron scattering and space charge transfer is proposed to comprehensively improve gas sensing performance of n-type metal oxides toward oxidizing NO2 (electron acceptor) at RT. To this end, the porous SnO2 nanoparticles (NPs) assembled from grains of about 4 nm with rich oxygen vacancies are developed through an acetylacetone-assisted solvent evaporation approach combined with precise N2 and air calcinations. The results show that the as-fabricated porous SnO2 NPs sensor exhibits an unprecedented NO2 -sensing performance, including outstanding response (Rg /Ra  = 772.33 @ 5 ppm), fast recovery (<2 s), an extremely low detection limit (10 ppb), and exceptional selectivity (response ratio >30) at RT. Theoretical calculation and experimental tests confirm that the excellent NO2 sensing performance is mainly attributed to the unique synergistic effect of electron scattering and space charge transfer. This work proposes a useful strategy for developing high-performance RT NO2 sensors using metal oxides, and provides an in-depth understanding for the basic characteristics of the synergistic effect on gas sensing, paving the way for efficient and low power consumption gas detection at RT.

Preparation of fat substitute based on maize starch hydrolysates and application in reduced-fat acidified milk gel.

Reduced-fat food has become a popular choice among contemporary consumers. This study aims to develop a starch-based fat substitute and incorporate it into reduced-fat milk gel acidified with glucono-δ-lactone (GDL) to achieve similar rheological properties as a full-fat gel. The gel properties of the fat substitute were assessed. The study examined the rheological properties, syneresis, textural properties and microstructure of acidified milk gels while also monitoring acidification process. Starch hydrolysates with low dextrose equivalent (DE) (<5.1 %) can serve as an effective fat substitute due to their excellent gelling properties The rheological and textural properties of the reduced-fat acidified milk gel with DE at 3.1 % of starch hydrolysate and 30 % fat substitution are similar to those of the full-fat milk gel. The syneresis and confocal laser scanning microscopy (CLSM) results indicated that the microstructure of the reduced-fat acidified milk gel was similar to the full-fat version. Moreover, the sensory properties of the reduced-fat acidified milk gel were acceptable when the DE was 3.1 %, and 30 % fat was replaced. In our study, we utilized hydrolyzed starch to produce reduced-fat acidified milk gels, which could potentially be used in the development of reduced-fat yogurt formulations.

HDAC3 deficiency protects against acute lung injury by maintaining epithelial barrier integrity through preserving mitochondrial quality control.

Sepsis is one common cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which is closely associated with high mortality in intensive care units (ICU). Histone deacetylase 3 (HDAC3) serves as an important epigenetic modifying enzyme which could affect chromatin structure and transcriptional regulation. Here, we explored the effects of HDAC3 in type II alveolar epithelial cells (AT2) on lipopolysaccharide (LPS)-induced ALI and shed light on potential molecular mechanisms. We generated ALI mouse model with HDAC3 conditional knockout mice (Sftpc-cre; Hdac3f/f) in AT2 and the roles of HDAC3 in ALI and epithelial barrier integrity were investigated in LPS-treated AT2. The levels of HDAC3 were significantly upregulated in lung tissues from mice with sepsis and in LPS-treated AT2. HDAC3 deficiency in AT2 not only decreased inflammation, apoptosis, and oxidative stress, but also maintained epithelial barrier integrity. Meanwhile, HDAC3 deficiency in LPS-treated AT2 preserved mitochondrial quality control (MQC), evidenced by the shift of mitochondria from fission into fusion, decreased mitophagy, and improved fatty acid oxidation (FAO). Mechanically, HDAC3 promoted the transcription of Rho-associated protein kinase 1 (ROCK1) in AT2. In the context of LPS stimulation, the upregulated ROCK1 elicited by HDAC3 could be phosphorylated by Rho-associated (RhoA), thus disturbing MQC and triggering ALI. Furthermore, we found that forkhead box O1 (FOXO1) was one of transcription factors of ROCK1. HDAC3 directly decreased the acetylation of FOXO1 and promoted its nuclear translocation in LPS-treated AT2. Finally, HDAC3 inhibitor RGFP966 alleviated epithelial damage and improved MQC in LPS-treated AT2. Altogether, HDAC3 deficiency in AT2 alleviated sepsis-induced ALI by preserving mitochondrial quality control via FOXO1-ROCK1 axis, which provided a potential strategy for the treatment of sepsis and ALI.

The Role of Histone Deacetylases in Acute Lung Injury-Friend or Foe.

Acute lung injury (ALI), caused by intrapulmonary or extrapulmonary factors such as pneumonia, shock, and sepsis, eventually disrupts the alveolar-capillary barrier, resulting in diffuse pulmonary oedema and microatasis, manifested by refractory hypoxemia, and respiratory distress. Not only is ALI highly lethal, but even if a patient survives, there are also multiple sequelae. Currently, there is no better treatment than supportive care, and we urgently need to find new targets to improve ALI. Histone deacetylases (HDACs) are epigenetically important enzymes that, together with histone acetylases (HATs), regulate the acetylation levels of histones and non-histones. While HDAC inhibitors (HDACis) play a therapeutic role in cancer, inflammatory, and neurodegenerative diseases, there is also a large body of evidence suggesting the potential of HDACs as therapeutic targets in ALI. This review explores the unique mechanisms of HDACs in different cell types of ALI, including macrophages, pulmonary vascular endothelial cells (VECs), alveolar epithelial cells (AECs), and neutrophils.

Purification and identification of xanthine oxidase inhibitory peptides from enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein.

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.

Low-fat ice cream model system: impact of incorporation of alcalase hydrolyzed zein.

Research on fat substitutes with low calories and good flavor is important to reduce the fat content in food. In this paper, the selection of fat substitutes and the preparation of low-fat ice cream were carried out through looking at the emulsion properties of the enzymatic hydrolysis of zein. The results showed that the emulsifying activity of zein after enzymatic hydrolysis for 10 min was 66.76 m2 g-1, and the emulsifying stability was 78.51 min, showing the best emulsifying properties. Enzymatic hydrolysis of zein can effectively reduce the degree of lipid oxidation. The protein digestibility in intestinal juice was also significantly improved, and the release rate of free fatty acids in the emulsion reached more than 80%. The viscosity, shear stress, elastic modulus, electronic nose and electronic tongue of ice cream with 10% oil substitute were close to those of full-fat ice cream. It is expected to provide a basis for the development of functional foods.