Breast Milk Enema and Meconium Evacuation Among Preterm Infants: A Randomized Clinical Trial.

Importance: Delayed meconium evacuation and delayed achievement of full enteral feeding among premature infants are associated with poor short- and long-term outcomes. Identifying a more effective and safer enema for meconium evacuation is imperative for improving neonatal care. Objective: To examine whether breast milk enemas can shorten the time to complete meconium evacuation and achievement of full enteral feeding for preterm infants. Design, Setting, and Participants: This randomized, open-label, parallel-group, single-center clinical trial was conducted from September 1, 2019, to September 30, 2022, among 286 preterm infants with a gestational age of 23 to 30 weeks in the neonatal ward of the Shengjing Hospital of China Medical University in Shenyang. Interventions: Preterm infants were randomly assigned to receive either breast milk enemas or normal saline enemas 48 hours after birth. Main Outcome and Measures: The primary outcomes were time to complete meconium evacuation and time to achieve full enteral feeding. Secondary outcomes were duration of hospitalization, weight at discharge, and duration of total parenteral nutrition. Intention-to-treat and per-protocol analyses were conducted. Results: In total, 286 preterm infants (mean [SD] gestational age, 198.8 [7.9] days; 166 boys [58.0%]) were eligible and included in this study. A total of 145 infants were randomized to the normal saline group, and 141 were randomized to the breast milk group. The time to achieve complete meconium evacuation was significantly shorter in the breast milk group than in the normal saline group (-2.2 days; 95% CI, -3.2 to -1.2 days). The time to achieve full enteral feeding was also significantly shorter in the breast milk group than in the normal saline group (-4.6 days; 95% CI, -8.0 to -1.2 days). The duration of total parenteral nutrition was significantly shorter in the breast milk group than in the normal saline group (-4.6 days; 95% CI, -8.6 to -1.0 days). There were no clinically notable differences in any other secondary or safety outcomes between the 2 groups. Conclusions and Relevance: In this randomized clinical trial testing the effects of breast milk enema on meconium evacuation, breast milk reduced the time to achieve complete meconium evacuation and achieve full enteral feeding for preterm infants with a gestational age of 23 to 30 weeks. Subgroup analyses highlight the need for tailored interventions based on gestational age considerations. Trial Registration: isrctn.org Identifier: ISRCTN17847514.

LettuceDB: an integrated multi-omics database for cultivated lettuce.

Crop genomics has advanced rapidly during the past decade, which generated a great abundance of omics data from multi-omics studies. How to utilize the accumulating data becomes a critical and urgent demand in crop science. As an attempt to integrate multi-omics data, we developed a database, LettuceDB (https://db.cngb.org/lettuce/), aiming to assemble multidimensional data for cultivated and wild lettuce germplasm. The database includes genome, variome, phenome, microbiome and spatial transcriptome. By integrating user-friendly bioinformatics tools, LettuceDB will serve as a one-stop platform for lettuce research and breeding in the future. Database URL: https://db.cngb.org/lettuce/.

Genome-wide investigation of UDP-Glycosyltransferase family in Tartary buckwheat (Fagopyrum tataricum).

BACKGROUND: Tartary buckwheat (Fagopyrum tataricum) belongs to Polygonaceae family and has attracted increasing attention owing to its high nutritional value. UDP-glycosyltransferases (UGTs) glycosylate a variety of plant secondary metabolites to control many metabolic processes during plant growth and development. However, there have been no systematic reports of UGT superfamily in F. tataricum. RESULTS: We identified 173 FtUGTs in F. tataricum based on their conserved UDPGT domain. Phylogenetic analysis of FtUGTs with 73 Arabidopsis UGTs clustered them into 21 families. FtUGTs from the same family usually had similar gene structure and motif compositions. Most of FtUGTs did not contain introns or had only one intron. Tandem repeats contributed more to FtUGTs amplification than segmental duplications. Expression analysis indicates that FtUGTs are widely expressed in various tissues and likely play important roles in plant growth and development. The gene expression analysis response to different abiotic stresses showed that some FtUGTs were involved in response to drought and cadmium stress. Our study provides useful information on the UGTs in F. tataricum, and will facilitate their further study to better understand their function. CONCLUSIONS: Our results provide a theoretical basis for further exploration of the functional characteristics of FtUGTs and for understanding the growth, development, and metabolic model in F. tataricum.

Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking.

The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.

Modified Buyang Huanwu Decoction alleviates diabetic liver injury via inhibiting oxidative stress in db/db mice.

OBJECTIVES: In diabetes, chronic hyperglycemia increases the overactivation of oxidative phosphorylation of mitochondria in the liver, resulting in oxidative stress (OS) damage. The Nrf2 signaling pathway plays a key role in preventing hepatic oxidative injury and inflammation. This study aims to investigate the therapeutic effect and mechanism of Modified Buyang Huanwu Decoction (mBYHWD) on diabetic liver injury (DLI) by regulating oxidative stress mediated by Nrf2 signaling pathway. METHODS: The experiment was divided into three groups: a control group (db/m mice, Con), a diabetes model group (db/db mice, Mod), and a traditional Chinese medicine group (db/m mice, mBYHWD). Post-treatment, serum from each group was analyzed to assess changes of blood glucose, blood lipid, and liver function. These results were combined with data mining to explore the possible pathogenesis of DLI. Liver tissues were collected to observe the pathological morphology and detect related proteins. RESULTS: The results demonstrated that mBYHWD significantly reduced blood lipids and improved liver function following diabetic liver injury. The histopathological results demonstrated that mBYHWD could significantly ameliorate damage of diabetic hepatocytes. Protein analysis revealed that mBYHWD treatment significantly increased the expression of antioxidant proteins in diabetic liver tissue and inhibited inflammation. CONCLUSIONS: The therapeutic mechanism of mBYHWD on DLI may involve activating the Nrf2 signaling pathway to improve oxidative stress, inhibit inflammation, and reduce liver tissue fibrosis.

Effect of Tai Chi vs Aerobic Exercise on Blood Pressure in Patients With Prehypertension: A Randomized Clinical Trial.

Importance: Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective: To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants: This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions: Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures: The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results: Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance: In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.

Effects of dietary addition of ellagic acid on rumen metabolism, nutrient apparent digestibility, and growth performance in Kazakh sheep.

Plant extracts have shown promise as natural feed additives to improve animal health and growth. Ellagic acid (EA), widely present in various plant tissues, offers diverse biological benefits. However, limited research has explored its effects on ruminants. This study aimed to investigate the effects of dietary addition EA on rumen metabolism, apparent digestibility of nutrients, and growth performance in Kazakh sheep. Ten 5-month-old Kazakh sheep with similar body weight (BW), fitted with rumen fistulas, were randomly assigned to two groups: the CON group (basal diet) and the EA group (basal diet + 30 mg/kg BW EA). The experiment lasted 30 days, and individual growth performance was assessed under identical feeding and management conditions. During the experimental period, rumen fluid, fecal, and blood samples were collected for analysis. The results indicated a trend toward increased average daily gain in the EA group compared to the CON group (p = 0.094). Compared with the CON group, the rumen contents of acetic acid and propionic acid were significantly increased in the EA group and reached the highest value at 2 h to 4 h after feeding (p < 0.05). Moreover, the relative abundances of specific rumen microbiota (Ruminococcaceae, uncultured_rumen_bacterium, unclassified_Prevotella, Bacteroidales, Bacteroidota, Bacteroidia, unclassified_Rikenellaceae, and Prevotella_spBP1_145) at the family and genus levels were significantly higher in the EA group (p < 0.05) compared to the CON group. The EA group exhibited significantly higher dry matter intake (p < 0.05) and increased the digestibility of neutral detergent fiber and ether extract when compared with the CON group (p < 0.05). Additionally, the plasma activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly higher, while malondialdehyde (MDA) concentration was significantly lower in the EA group compared to the CON group (p < 0.05). In conclusion, dietary supplementation with 30 mg/kg BW EA in 5-month-old Kazakh sheep increased the dry matter intakQ16e, apparent digestibility of neutral detergent fiber, and ether extract, as well as the contents of acetic acid and propionic acid in rumen fluid. Moreover, EA supplementation regulated the ruminal microbiota, enhanced antioxidant capacity, and improved daily weight gain.

The application of demographic characteristics of Ectropis grisescens (Lepidoptera: Geometridae) in pest risk assessment of IPM.

Ectropis grisescens Warren is one of the most important pests of tea plants. In this study, data on the development, survival, and fecundity of E. grisescens were collected at 15, 22, and 32 °C and analyzed by using the age-stage, two-sex life table. At 15 °C, the duration of the preadult period of E. grisescens was significantly prolonged (81.06 days), with high mortality (69.0%), and the proportion of emerged female adults was extremely low (7.0%). At 32 °C, the preadult period was significantly shortened (29.12 days), with high preadult mortality (74.0%), and a low proportion of emerged female adults (15.0%). At 22 °C, with low preadult mortality (24.0%), and a high proportion of emerged female adults (26.0%). The overall effects of the shorter preadult duration, higher preadult survival rate, higher proportion of emerged female adults, higher fecundity (F = 350.88 eggs/♀), and higher net reproductive rate (R0 = 91.23 offspring/individual) at 22 °C resulted in the highest values of the intrinsic rate of increase (r = 0.1054 days-1) and finite rate of increase (λ = 1.1112 days-1). Computer simulation showed that E. grisescens populations can increase much faster at 22 °C than at 15 and 32 °C. The weighted population size and cumulative weighted insect-days provided the dynamics necessary for estimating the damage potential of E. grisescens in devising economical pest management programs. Our results demonstrate that populations of E. grisescens were able to develop at a broad range of temperatures and adapt to the high temperatures. These finding can be utilized to improve the management of E. grisescens.

Phosphorus Footprint in the Whole Biowaste-Biochar-Soil-Plant System: Reservation, Replenishment, and Reception.

Two phosphorus (P)-rich biowastes, sewage sludge (SS) and bone dreg (BD), were selected to clarify P footprints among biowaste, biochar, soil, and plants by introducing a novel "3R" concept model. Results showed that pyrolysis resulted in P transformation from an unstable-organic amorphous phase to a stable-inorganic crystalline phase with a P retention rate of 70-90% in biochar (P reservation). In soil, SSBC released more P in acid red soil and alkaline yellow soil than BDBC, while the opposite result appeared in neutral paddy soil. The P released from SSBC formed AlPO4 by combining with Al in soil, whereas P from BDBC transformed into Ca5(PO4)3F(or Cl) in conjunction with Ca in the soil (P replenishment). Various plants exhibited an uptake of approximately 2-6 times more P from biochar-amended soil than from the original soil (P reception). This study can guide the application of biochar in various soil-plant systems for effective nutrient reclamation.

A facile boronophenylalanine modified polydopamine dual drug-loaded nanoparticles for enhanced anti-tumor immune response in hepatocellular carcinoma comprehensive treatment.

Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.

Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson's disease after dietary supplementation with branched-chain amino acids.

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial-gut-brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson's disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography-mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Effects of Traditional Chinese Medicine Five-Element Music Therapy Combined with Mirtazapine on Depression and Limb Function Recovery After Ischemic Stroke.

Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets.

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Molecular Mechanism by Which TRPC6 Regulates Calcium Signaling and Neuroinflammation in the Onset and Development of Ischemic Stroke: A Review.

Cerebral infarction, also known as ischemic stroke, is caused by various regional blood supply disorders in the brain tissue, leading to ischemic hypoxic lesions and necrosis of the brain tissue and then the corresponding clinical manifestations of neurological loss, which has high mortality and disability. This study comprehensively reviews the potential molecular mechanisms of TRPC6 in neuroprotection in cerebral infarction and provides a summary of TRPC6 as a targeted drug or prognostic biomarker for cerebral infarction patients. We will screen and synthesize evidence about the molecular mechanisms of TRPC6 in cerebral infarction from the current literature to obtain comprehensive knowledge on this topic. In the pathogenesis, neuroinflammation and intracellular calcium accumulation play an important role in the onset and development of cerebral infarction. Transient receptor potential cation channel subfamily C6 (TRPC6) is the main component of calcium store-operated calcium channels. It plays a central role in ischemic cerebrovascular disease by mediating the calcium ion signaling pathway. In this review, evidence on the neuroprotective effects of TRPC6 has been shown, including inhibiting neuroinflammation and inhibiting nerve cell apoptosis, thereby alleviating nerve injury. However, at the same time, TRPC6 promotes inflammation in other organs. Generally, although an increasing number of researches support the protective role of TRPC6 in cerebral infarction, there is still evidence showing that overexpression of TRPC6 increases inflammatory tissue damage in other organs. Therefore, clarifying the molecular mechanism of TRPC6 will help develop targeted drugs or prognostic biomarkers for cerebral infarction to promote and predict neurological function recovery. More evidence to elucidate the molecular mechanism of TRPC6 in cerebral infarction is needed. Enriching TRPC6 in neuroinflammation areas and modifying its cell specificity might be the orientation of drug development that increases the effect of stroke treatment and reduces the impact on other organs. In conclusion, in cerebral infarction, TRPC6 has been proven to alleviate neuroinflammation and inhibit nerve cell apoptosis. However, at the same time, TRPC6 may promote inflammation in other organs. Therefore, the targeting potential of TRPC6 in cerebral infarction needs to be further explored.

Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

Assessment of the anti-inflammatory mechanism of quercetin 3,7-dirhamnoside using an integrated pharmacology strategy.

Pouzolzia zeylanica (L.) Benn. is a Chinese herbal medicine widely used for its anti-inflammatory and pus-removal properties. To explore its potential anti-inflammatory mechanism, quercetin 3,7-dirhamnoside (QDR), the main flavonoid component of P. zeylanica (L.) Benn., was extracted and purified. The potential anti-inflammatory targets of QDR were predicted using network analysis. These potential targets were verified using molecular docking, molecular dynamics simulations, and in vitro experiments. Consequently, 342 potential anti-inflammatory QDR targets were identified. By analyzing the intersection between the protein-protein interaction and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified several potential protein targets of QDR, including RAC-alpha serine/threonine-protein kinase (AKT1), Ras-related C3 botulinum toxin substrate 1 (RAC1), nitric oxide synthase 3 (NOS3), serine/threonine-protein kinase mTOR (mTOR), epidermal growth factor receptor (EGFR), growth factor receptor-bound protein 2 (GRB2), and endothelin-1 receptor (EDNRA). QDR has anti-inflammatory activity and regulates immune responses and apoptosis through chemokines, Phosphatidylinositol 3-kinase 3(PI3K)/AKT, cAMP, T-cell receptor, and Ras signaling pathways. Molecular docking analysis showed that QDR has good binding abilities with AKT1, mTOR, and NOS3. In addition, molecular dynamics simulations demonstrated that the protein-ligand complex systems formed between QDR and AKT1, mTOR, and NOS3 have high dynamic stability, and their protein-ligand complex systems possess strong binding ability. In RAW264.7 macrophages, QDR significantly inhibited lipopolysaccharides (LPS)-induced inducible nitric oxide synthase expression, nitric oxide (NO) release and the generation of proinflammatory cytokines IL-6, IL-1ß, and TNF-α. QDR downregulated the expression of p-AKT1(Ser473)/AKT1 and p-mTOR (Ser2448)/mTOR, and upregulated the expression of NOS3, Rictor, and Raptor. This indicates that the anti-inflammatory mechanisms of QDR involve regulation of AKT1 and mTOR to prevent apoptosis and of NOS3 which leads to the release of endothelial NO. Thus, our study elucidated the potential anti-inflammatory mechanism of QDR, the main flavonoid found in P. zeylanica (L.) Benn.

Nutrient-Based Approaches for Melanoma: Prevention and Therapeutic Insights.

Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in understanding its pathogenesis and treatment, the quest for effective prevention strategies and therapeutic approaches remains ongoing. Considering the increased advancements in understanding the dynamic interplay between nutrients and melanoma, we aim to offer a refreshed perspective on nutrient-based approaches for melanoma prevention and adjunctive therapy. In contrast to other studies, we have innovatively provided a detailed exposition of the nutrients' influences on melanoma prognosis and treatment. This review firstly examines various nutrients, including antioxidants (namely vitamins A, D, C, and E; selenium; and caffeine), polyunsaturated fatty acids, and flavonoids, for their effects and underlying mechanisms in reducing melanoma risk. Among these nutrients, caffeine shows the most promising potential, as it is supported by multiple cohort studies for its protective effect against melanoma. In contrast, there is a certain degree of inconsistency in the research of other nutrients, possibly due to inherent differences between animal studies and epidemiological research, as well as variations in the definition of nutrient intake. To comprehensively investigate the impact of nutrients on melanoma progression and therapeutic approaches, the following sections will explore how nutrients influence immune responses and other physiological processes. While there is robust support from cell and animal studies regarding the immunomodulatory attributes of vitamins D and zinc, the anti-angiogenic potential of polyphenols, and the cell growth-inhibitory effects of flavonoids, the limited availability of human-based research substantially constrains their practical relevance in clinical contexts. As for utilizing nutrients in adjuvant melanoma treatments, multiple approaches have garnered clinical research support, including the utilization of vitamin D to decrease the postoperative recurrence rates among melanoma patients and the adoption of a high-fiber diet to enhance the effectiveness of immunotherapy. In general, the effects of most nutrients on reducing the risk of melanoma are not entirely clear. However, several nutrients, including vitamin D and dietary fiber, have demonstrated their potential to improve the melanoma prognosis and enhance the treatment outcomes, making them particularly deserving of clinical attention. A personalized and interdisciplinary approach, involving dermatologists, oncologists, nutritionists, and researchers, holds the promise of optimizing melanoma treatment strategies.

Albumin-based nanosystem for dual-modality imaging-guided chem-phototherapy against immune-cold triple-negative breast cancer.

Triple-negative breast cancer is a highly aggressive and metastatic tumor; diagnosing it in the early stages is still difficult, and the prognosis for conventional radio-chemotherapy and immunotreatment is not promising due to cancer's immunosuppressive microenvironment. The utilization of protein-based nanosystem has proven to be effective in delivering agents with limited adverse effects, yet the combination of diagnosis and treatment remains a difficult challenge. This research took advantage of natural albumin and organic molecules to construct a self-assemble core-shell nanostructure combining with superparamagnetic iron oxide nanocrystals and heptamethine cyanine dye IR780 through non-covalent interactions. This nanocomposite successfully decreased the transverse relaxation time of the magnetic resonance hydrogen nucleus, resulting in outstanding T2 imaging, as well as emitting near-infrared II fluorescence, thereby the resulting dual-modality imaging tool was applied to improve diagnostic competency. It is noteworthy that the nanocomposites exhibited impressive enzyme-like catalytic and photothermal capabilities, resulting in a successful activation of the immune system to efficiently suppress distant metastatic lesions in vivo. Consequently, this nano-drug-based therapy could be an advantageous asset in reinforcing the immune system and hindering the growth and reappearance of the immune-cold breast cancer.

Relationship between Bladder Cancer, Nutritional Supply, and Treatment Strategies: A Comprehensive Review.

Bladder cancer (BC) is the predominant neoplasm affecting the urinary system and ranks among the most widespread malignancies globally. The causes of bladder cancer include genetic factors; age; sex; and lifestyle factors, such as imbalanced nutrition, obesity, and metabolic disorders. The lack of proper nutrient intake leads to the development of bladder cancer because insufficient nutrients are consumed to prevent this disease. The purpose of this review was to analyze the nutrients closely linked to the onset and advancement of bladder cancer and to explore the relationship between dietary nutrients and bladder cancer. Particular emphasis was placed on nutrients that are frequently ingested in daily life, including sugar, fat, protein, and others. The focus of this research was to analyze how nutritional intake before and after surgery affects the recovery process of patients who have been diagnosed with bladder cancer. This article seeks to increase awareness among both society and the medical community about the significance of implementing appropriate dietary nutrition to reduce the chances of developing bladder cancer, enhance perioperative care for patients with bladder cancer, and aid in their recuperation.

Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1ß, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.