Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology.

Background: The ginseng polysaccharide injection is a well-known traditional Chinese medicine often employed as a supplementary treatment for cancer. This treatment can not only alleviate the adverse effects caused by tumor radiotherapy and chemotherapy but also enhance the immune system of individuals diagnosed with lung cancer. It is important to acknowledge the efficacy of ginseng polysaccharide injection in the treatment of non-small cell lung cancer (NSCLC). However, these small-sample studies may have certain biases, and the underlying mechanisms of ginseng polysaccharides therapy for NSCLC are still unclear. Methods: The present study involved a systematic review of the literature on randomized controlled trials (RCTs) focusing on using ginseng polysaccharide injection as a therapeutic approach for NSCLC. Seven databases were searched for eligible studies published before April 2023. Two researchers independently managed data extraction, risk of bias assessment, and data analyses using RevMan 5.3 software. In network pharmacology, we thoroughly searched the relevant literature on ginseng polysaccharides (GPs) and the PubChem database. This search aimed to identify the main active ingredients and targets associated with ginseng polysaccharides. Subsequently, we compared these targets with those of NSCLC and utilized bioinformatics techniques to analyze and explore their potential interactions. Results: A total of 11 RCTs involving 845 patients with NSCLC were included in the meta-analysis. The meta-analysis revealed that ginseng polysaccharide injection combined significantly improved the objective response rate [RR = 1.45, 95% CI (1.26, 1.67), P < 0.00001]. Furthermore, it was observed that ginseng polysaccharide injection increased the serum levels of CD4+ T-lymphocytes (CD4+ T) [MD = 8.98, 95% CI (5.18, 12.78), P < 0.00001], and decreased the serum levels of CD8+ T-lymphocytes (CD8+ T) [MD = -2.68, 95% CI (-4.66, -0.70), P = 0.008]. Through network pharmacology analysis, a total of 211 target genes of GPs and 81 common targets were identified. GAPDH, EGFR, VEGFA, JUN, SRC, CASP3, STAT3, CCND1, HSP90AA1, and MMP9 were identified as the core target proteins. Additionally, KEGG enrichment analysis revealed 122 relevant signaling pathways, including Pathways in cancer, PD-L1 expression and PD-1 checkpoint pathway in cancer, and Proteoglycans in cancer. Conclusion: Ginseng polysaccharide injection can improve the ORR of patients with NSCLC, increase the serum levels of CD4+ T, and decrease the serum levels of CD8+ T. The potential mechanism may be associated with the PD-1/PD-L1 signaling pathway.

Regulatory mechanism of perinatal nonylphenol exposure on cardiac mitochondrial autophagy and the PINK1/Parkin signaling pathway in male offspring rats.

OBJECTIVE: This study investigated whether perinatal exposure to nonylphenol (NP) induces mitochondrial autophagy (i.e., mitophagy) damage in neonatal rat cardiomyocytes (NRCMs) and whether the PINK1/Parkin signaling pathway is involved in NP-induced primary cardiomyocyte injury. METHODS AND RESULTS: In vivo: Perinatal NP exposure increased apoptosis and mitochondrial damage in NRCMs. Mitochondrial swelling and autophagosome-like structures with multiple concentric membranes were observed in the 100 mg/kg NP group, with an increase in the number of autophagosomes. Disorganized fiber arrangement and elevated serum myocardial enzyme levels were observed with increasing NP dosage. Additionally, NP exposure led to increased MDA levels and decreased SOD activity and ATP levels in myocardial tissue. The mRNA expression levels of autophagy-related genes, including Beclin-1, p62, and LC3B, as well as the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, p62, LC3-I, LC3-II, and LC3-II/I) and apoptosis-related proteins (Bax and caspase-3), increased, whereas the expression levels of the mitochondrial membrane protein TOMM20 and the anti-apoptotic protein Bcl-2 decreased. In vitro: NP increased ROS levels, LDH release, and decreased ATP levels in NRCMs. CsA treatment significantly inhibited the expression of autophagy-related proteins (Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased the expression levels of TOMM20 and Bcl-2 proteins, increased cellular ATP levels, and inhibited LDH release. The inhibition of the PINK1/Parkin signaling pathway suppressed the expression of mitochondrial autophagy-related proteins (PINK1, p-Parkin, Parkin, Beclin-1, LC3-II/I, and p62) and apoptosis-related proteins (caspase-3 and Bax), increased TOMM20 and Bcl-2 protein expression, increased ATP levels, and decreased LDH levels in NRCMs. CONCLUSIONS: This study is novel in reporting that perinatal NP exposure induced myocardial injury in male neonatal rats, thereby inducing mitophagy. The PINK1/Parkin signaling pathway was involved in this injury by regulating mitophagy.

ZmARF1 positively regulates low phosphorus stress tolerance via modulating lateral root development in maize.

Phosphorus (P) deficiency is one of the most critical factors for plant growth and productivity, including its inhibition of lateral root initiation. Auxin response factors (ARFs) play crucial roles in root development via auxin signaling mediated by genetic pathways. In this study, we found that the transcription factor ZmARF1 was associated with low inorganic phosphate (Pi) stress-related traits in maize. This superior root morphology and greater phosphate stress tolerance could be ascribed to the overexpression of ZmARF1. The knock out mutant zmarf1 had shorter primary roots, fewer root tip number, and lower root volume and surface area. Transcriptomic data indicate that ZmLBD1, a direct downstream target gene, is involved in lateral root development, which enhances phosphate starvation tolerance. A transcriptional activation assay revealed that ZmARF1 specifically binds to the GC-box motif in the promoter of ZmLBD1 and activates its expression. Moreover, ZmARF1 positively regulates the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key transporters of Pi in maize. We propose that ZmARF1 promotes the transcription of ZmLBD1 to modulate lateral root development and Pi-starvation induced (PSI) genes to regulate phosphate mobilization and homeostasis under phosphorus starvation. In addition, ZmERF2 specifically binds to the ABRE motif of the promoter of ZmARF1 and represses its expression. Collectively, the findings of this study revealed that ZmARF1 is a pivotal factor that modulates root development and confers low-Pi stress tolerance through the transcriptional regulation of the biological function of ZmLBD1 and the expression of key Pi transport proteins.

A universal dual-mode hydrogel array based on phage-DNA probe for simultaneous rapid screening and precisely quantitative detection of Escherichia coli O157:H7 in foods by the fluorescent/microfluidic chip electrophoresis methods.

Rapid and specific detection of virulent bacterial strains is a great challenge for food safety regarding large amounts of contaminated samples. Herein, a dual-mode hydrogel array biosensor was constructed to simultaneously rapidly screen and precisely quantitatively detect virulent Escherichia coli O157:H7 (E. coli O157:H7) based on a novel DNA-modified phage probe. First, E. coli O157:H7 was incubated with alginate to form the E. coli O157:H7/hydrogel premix complex. Subsequently, hydrogel formation by cross-linking upon the addition of calcium ions and phages for E. coli O157:H7 modified with a DNA primer (phage-DNA) was added to the alginate hydrogel. The DNA on the complex could trigger rolling circle amplification (RCA) to form a phage probe containing a long-chain DNA skeleton (phage@RCA-DNA). The RCA-DNA was then hybridized with the complementary DNA (cDNA) to form double-stranded DNA fragments (phage@RCA-dsDNA), which could be stained by the SYBR Green dye to emit visual green fluorescence (FL) and determined by a smartphone for rapid screening. Meanwhile, the unreacted cDNA in the supernatant could be quantitatively detected by microfluidic chip electrophoresis (MCE). The signal decrement was also proportional to the bacterial concentration. The detection limit values of E. coli O157:H7 were 50 CFU mL-1 by the FL signal and 6 CFU mL-1 by the MCE signal. The two results could be mutually corrected to decrease the false-positive results. This assay was also employed to detect virulent Salmonella Typhimurium (S. Typhimurium) using the corresponding S. Typhimurium phage@RCA-DNA probe. All these results demonstrated that the universal bioassay was suitable for simultaneous rapid screening and precisely quantitative detection of virulent bacterial strains.

The safety evaluation of Shenze Shugan capsule and mechanism of apoptosis induced by five potentially nephrotoxic components.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenze Shugan capsule is a prescription of traditional Chinese medicine for nonalcoholic steatohepatitis treatment. It includes Rhei Radix et Rhizoma (RR), Cassiae Semen (CS) and Alismatis Rhizoma(AR), which widely contains rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. AIM OF THE STUDY: In this study, we aimed to explore the safety of the medicine, and further elucidate the mechanism of apoptosis induction in HK-2 cells by five components, including rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. MATERIALS AND METHODS: We investigated the nephrotoxicity of Shenze Shugan capsule, including RR, CS, AR and mixed herbs given for two months in rats. Superoxide dismutase (SOD) in kidney tissues, urea nitrogen (BUN) and creatinine (CRE) in serum were detected, and renal pathology analysis was performed. In cell experiments, the apoptotic rate and cell cycle distribution of HK-2 cells were tested by flow cytometry. The levels of mitochondrial membrane potential (ΔΨm) and related protein expression in mitochondrial pathway were measured as well. RESULTS: We confirmed that two months of administering high doses(60 times the dose for clinical use in adults) of RR, CS or mixed herbs upregulated the levels of CRE and RUN, inhibited SOD activity, and increased the degree of tubular degeneration and glomerular dilatation, but Shenze Shugan capsule has no significant differences in renal structure or renal function. In addition, we found that five components all concentration-dependently inhibited HK-2 cells proliferation and induced apoptosis, especially aurantio-obtusin as the novel nephrotoxic component. Rhein and emodin significantly induced S/M accumulation, but aurantio-obtusin, alisol A and alisol B 23-monoacetate significantly induced G1/M accumulation in HK-2 cells. Similarly, they could induce Caspase3 activation, loss of mitochondrial membrane potential (ΔΨm), and down-regulation of Bcl-2 and up-regulation of Bax. CONCLUSIONS: Through a two-month subchronic toxicity study in rats, our preliminary determination is that this formulation is safe and reliable for long-term use. Interestingly, the potentially toxic herbs such as RR, CS, AR can reduce toxicity by drug compatibility. When further exploring the mechanism of action of toxic herbs, we found that mitochondrial pathway is involved in the apoptosis of HK -2 cells induced by rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. Our findings provide new ideas for safety studies of Shenze Shugan capsule.

Tumor microenvironment-activated theranostic nanozymes for trimodal imaging-guided combined therapy.

Synergistic therapy is expected to be a promising strategy for highly effective cancer treatment. However, the rational design of a simple and multifunctional nanoplatform still remains a grand challenge. Considering the nature of weak acidic, hypoxic, and H2O2 abundant tumor microenvironment, we constructed an indocyanine green (ICG) modified platinum nanoclusters (Pt NCs) decorated gold nanobipyramids (Au NBPs) to form the multifunctional nanocomposites (Au NBPs@Pt NCs-ICG) for multimodal imaging mediated phototherapy and chemodynamic cancer therapy. The photosensitizer ICG was covalently linked to Au NBPs@Pt NCs by bridging molecules of SH-PEG-NH2 for both photodynamic therapy (PDT) and fluorescence imaging. Besides, Au NBPs@Pt NCs-ICG nanocomposites exhibited catalase- and peroxidase-like activities to generate O2 and ·OH, which relieved the tumor hypoxia and upregulated antitumoral ROS level. Moreover, the combination of Au NBPs and ICG endowed the Au NBPs@Pt NCs-ICG with super photothermal conversion for effective photothermal imaging and therapy. In addition, the Au NBPs@Pt NCs-ICG nanoplatform displayed excellent X-ray computed tomography (CT) imaging ability due to the presence of high-Z elements (Au and Pt). Overall, our results demonstrated that Au NBPs@Pt NCs-ICG nanoplatform exhibited a multimodal imaging guided synergistic PTT/PDT/CDT therapeutic manners and held great potential as an efficient treatment for breast cancer.

Docosahexaenoic Acid-Acylated Astaxanthin Monoester Ameliorates Amyloid-ß Pathology and Neuronal Damage by Restoring Autophagy in Alzheimer's Disease Models.

SCOPE: Astaxanthin (AST) is ubiquitous in aquatic foods and microorganisms. The study previously finds that docosahexaenoic acid-acylated AST monoester (AST-DHA) improves cognitive function in Alzheimer's disease (AD), although the underlying mechanism remains unclear. Moreover, autophagy is reportedly involved in amyloid-ß (Aß) clearance and AD pathogenesis. Therefore, this study aims to evaluate the preventive effect of AST-DHA and elucidates the mechanism of autophagy modulation in Aß pathology. METHODS AND RESULTS: In the cellular AD model, AST-DHA significantly reduces toxic Aß1-42 levels and alleviated the accumulation of autophagic markers (LC3II/I and p62) in Aß25-35 -induced SH-SY5Y cells. Notably, AST-DHA restores the autophagic flux in SH-SY5YmRFP-GFP-LC3 cells. In APP/PS1 mice, a 3-month dietary supplementation of AST-DHA exceeded free-astaxanthin (F-AST) capacity to increase hippocampal and cortical autophagy. Mechanistically, AST-DHA restores autophagy by activating the ULK1 signaling pathway and restoring autophagy-lysosome fusion. Moreover, AST-DHA relieves ROS production and mitochondrial stress affecting autophagy in AD. As a favorable outcome of restored autophagy, AST-DHA mitigates cerebral Aß and p-Tau deposition, ultimately improving neuronal function. CONCLUSION: The findings demonstrate that AST-DHA can rectify autophagic impairment in AD, and confer neuroprotection in Aß-related pathology, which supports the future application of AST as an autophagic inducer for maintaining brain health.

Astaxanthin Augmented the Anti-Hepatocellular Carcinoma Efficacy of Sorafenib Through the Inhibition of the JAK2/STAT3 Signaling Pathway and Mitigation of Hypoxia within the Tumor Microenvironment.

SCOPE: The optimization of anti-cancer drug effectiveness through dietary modifications has garnered significant attention among researchers in recent times. Astaxanthin (AST) has been identified as a safe and biologically active dietary supplement. METHODS AND RESULTS: The tumor-bearing mice are treated with sorafenib, along with supplementation of 60 mg kg-1 AST during the treatment. The coadministration of AST and a subclinical dosage of 10 mg kg-1 sorafenib demonstrates a tumor inhibition rate of 76.5%, which is notably superior to the 45% inhibition rate observed with the clinical dosage of 30 mg kg-1 sorafenib (p < 0.05). The administration of AST leads to a tumor inhibition increase of around 25% when combined with the clinical dose of 30 mg kg-1 sorafenib (p <0.05). AST enhances the inhibitory effect of sorafenib on tumor angiogenesis through the JAK2/STAT3 signaling pathway. Furthermore, AST exhibits a reduction in hypoxia within the tumor microenvironment. CONCLUSION: The results suggest that AST supplement enhances the inhibitory effects of sorafenib on hepatocellular carcinoma. This study presents a new dietary management program for oncology patients.

Periplaneta americana extract promotes hard palate mucosal wound healing via the PI3K/AKT signaling pathway in male mice.

OBJECTIVES: This study aimed to investigate the effect of Periplaneta americana extract, a traditional Chinese medicine, on hard palate mucosal wound healing and explore the underlying mechanisms. DESIGN: Hard palate mucosal wound model was established and the effects of Periplaneta americana extract on hard palate mucosal wound healing were investigated by stereomicroscopy observation and histological evaluation in vivo. Human oral keratinocytes and human gingival fibroblasts, which play key roles in hard palate mucosal wound healing, were selected as the main research cells in vitro. The effects of Periplaneta americana extract on cell proliferation, migration, and collagen formation were determined by cell counting kit-8 (CCK-8) assay, Transwell assay, and Van Gieson staining. The underlying mechanism was revealed by RNA sequencing, and results were verified by western blot assay. RESULTS: Stereomicroscopy observation and H&E staining confirmed that Periplaneta americana extract accelerated the healing rate of hard palate mucosal wound (p < 0.001) in vivo. Transwell assay and Van Gieson staining assay showed that Periplaneta americana extract promoted the migration and collagen formation of human oral keratinocytes (p < 0.001) and human gingival fibroblasts (p < 0.001) in vitro. Mechanistically, RNA sequencing and western blot assay demonstrated that Periplaneta americana extract promoted hard palate mucosal wound healing via PI3K/AKT signaling, and the beneficial effects of Periplaneta americana extract were abrogated by the PI3K inhibitor LY294002. CONCLUSIONS: Periplaneta americana extract shows promising effects for the promotion of hard palate mucosal wound healing and may be a novel candidate for clinical translation.

Role and mechanism of MiR-542-3p in regulating TLR4 in nonylphenol-induced neuronal cell pyroptosis.

BACKGROUND: This study aimed to investigate the spatial learning/memory and motor abilities of rats and the alteration of miR-542-3p and pyroptosis in the midbrain nigrostriatal area in vivo after nonylphenol (NP) gavage and to explore the mechanism of miR-542-3p regulation of Toll-like receptor 4 (TLR4) in NP-induced pyroptosis in BV2 microglia in vitro. METHODS: In vivo: Thirty-six specific-pathogen-free-grade Sprague-Dawley rats were divided into three equal groups: blank control group (treated with pure corn oil), NP group (treated with NP, 80 mg/kg body weight per day for 90 days), and positive control group [treated with lipopolysaccharide (LPS), 2 mg/kg body weight for 7 days]. In vitro: The first part of the experiment was divided into blank group (control, saline), LPS group [1 µg/ml + 1 mM adenosine triphosphate (ATP)], and NP group (40 µmol/L). The second part was divided into mimics NC (negative control) group, miR-542-3p mimics group, mimics NC + NP group, and miR-542-3p mimics + NP group. RESULTS: In vivo: Behaviorally, the spatial learning/memory and motor abilities of rats after NP exposure declined, as detected via Y-maze, open field, and rotarod tests. Some microglia in the substantia nigra of the NP-treated rats were activated. The downregulation of miR-542-3p was observed in rat brain tissue after NP exposure. The mRNA/protein expression of pyroptosis-related indicators (TLR4), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), gasdermin-D (GSDMD), cysteinyl aspartate-specific proteinase-1 (caspase-1), and interleukin-1ß (IL-1ß) in the substantia nigra of the midbrain increased after NP exposure. In vitro: ASC fluorescence intensity increased in BV2 cells after NP exposure. The mRNA and/or protein expression of pyroptosis-related indicators (TLR4, NLRP3, GSDMD, caspase-1, and IL-1ß) in BV2 cells was upregulated after NP exposure. The transfection of miR-542-3p mimics inhibited NP-induced ASC expression in BV2 cells. The overexpression of miR-542-3p, followed by NP exposure, significantly reduced TLR4, NLRP3, ASC, caspase-1, and IL-1ß gene and/or protein expression. CONCLUSIONS: This study suggested that NP exposure caused a decline in spatial learning memory and whole-body motor ability in rats. Our study was novel in reporting that the upregulation of miR-542-3p targeting and regulating TLR4 could inhibit NLRP3 inflammatory activation and alleviate NP-induced microglia pyroptosis.

Kaempferol is a novel antiviral agent against channel catfish virus infection through blocking viral attachment and penetration in vitro.

Channel catfish virus (CCV, Ictalurid herpesvirus 1) is the causative pathogen of channel catfish virus disease, which has caused high mortality and substantial economic losses in the catfish aquaculture industry. Due to the lack of licensed prophylactic vaccines and therapeutic drugs, the prevention and control of CCV infection seem to remain stagnant. Active compounds from medicinal plants offer eligible sources of pharmaceuticals and lead drugs to fight against endemic and pandemic diseases and exhibit excellent effect against viral infection. In this study, we evaluated the antiviral ability of 12 natural compounds against CCV with cell models in vitro and found kaempferol exhibited the strongest inhibitory compound against CCV infection among all the tested compounds. Correspondingly, kaempferol decreased transcription levels of viral genes and the synthesis of viral proteins, as well as reduced proliferation and release of viral progeny, the severity of the CPE induced by CCV in a dose-dependent manner, based on quantitative real-time PCR (RT-qPCR), western blotting, viral cytopathic effects (CPE) and viral titer assessment. Moreover, time-of-drug-addition assays, virus attachment, and penetration assays revealed that kaempferol exerted anti-CCV activity probably by blocking attachment and internalization of the viral entry process. Altogether, the present results indicated that kaempferol may be a promising candidate antiviral agent against CCV infection, which shed light on the development of a novel and potent treatment for fish herpesvirus infection.

The Effect of Preoperative Anxiety State on Postoperative Intestinal Microecology and Gastrointestinal Function Recovery in Colorectal Cancer Patients.

Objective: To investigate the effect of preoperative anxiety status on postoperative intestinal microbiota and gastrointestinal function recovery in colorectal cancer patients with the aim of understanding the potential impact of psychological factors on surgical outcomes and improving patient care. Method: A total of 72 patients who underwent radical resection of colorectal cancer in our hospital from January 2017 to May 2020 were selected. According to the results of Hamilton Anxiety Scale (HAMA) on the day before surgery, the patients were divided into non-anxiety group (HAMA < 7 points) and an anxiety group (HAMA ≥ 7 points). The relationship between preoperative anxiety status and postoperative intestinal microecology and gastrointestinal function recovery in patients with colorectal cancer was analyzed. Results: The first exhaust time and the first defecation time in the non-anxiety group were shorter than those in the anxiety group (P < .05). The first complete eating time and postoperative hospitalization time of patients in the non-anxiety group were shorter than those in the anxiety group, and the total incidence of postoperative complications in the anxiety group was higher than that in the non-anxiety group (P < .05). There was no significant difference in the number of intestinal flora between the two groups before the operation (P > .05). The number of intestinal Lactobacillus and Bifidobacterium in the non-anxiety group was higher than that in the anxiety group at the first defecation and the 15th day after operation. The number of Escherichia coli and cocci was less than that of the anxiety group (P < .05). There was no significant difference in preoperative fecal sIgA levels between the two groups (P > .05). The level of fecal sIgA in the non-anxiety group was higher than that in the anxiety group at the first defecation and the 15th day after operation (P < .05). There was no significant difference in preoperative serum D-lactic acid between the two groups (P > .05). The serum D-lactic acid level and urinary L / M ratio in the non-anxiety group were lower than those in the anxiety group at the first defecation and the 15th day after operation (P < .05). Conclusion: Our study indicates that preoperative anxiety is associated with postoperative intestinal microbiota imbalance and delayed recovery of gastrointestinal function in colorectal cancer patients. These findings underscore the importance of addressing psychological factors in the care of these patients and suggest that interventions targeting anxiety may improve surgical outcomes and enhance patient recovery. Further research is needed to explore the mechanisms underlying these associations and to develop effective interventions to mitigate the negative impact of preoperative anxiety on postoperative recovery.

Pharmacological activities and therapeutic potential of galangin, a promising natural flavone, in age-related diseases.

BACKGROUND: The extension of average life expectancy and the aggravation of population aging have become the inevitable trend of human development. In an aging society, various problems related to medical care for the elderly have become increasingly prominent. However, most of the age-related diseases have the characteristics of multiple diseases at the same time, prone to complications, and atypical clinical manifestations, which bring great difficulties to its treatment. Galangin (3,5,7-trihydroxyflavone) is a natural active compound extracted from the root of Alpinia officinarum Hance (Zingiberaceae). Recently, many studies have shown that galangin has potential advantages in the treatment of neurodegenerative diseases and cardiovascular and cerebrovascular diseases, which are common in the elderly. In addition, it also showed that galangin had prospective activities in the treatment of tumor, diabetes, liver injury, asthma and arthritis. PURPOSE: This review aims to systematically summarize and discuss the effects and the underlying mechanism of galangin in the treatment of age-related diseases. METHODS: We searched PubMed, SciFinder, Web of Science and CNKI literature database resources, combined with the keywords "galangin", "neurodegenerative disease", "tumor", "diabetes", "pharmacological activity", "drug combination", "pharmacokinetics", "drug delivery system" and "safety", and comprehensively reviewed the pharmacological activities and mechanism of galangin in treating age-related diseases. RESULTS: According to the previous studies on galangin, the anti-neurodegenerative activity, cardiovascular and cerebrovascular protective activity, anti-tumor activity, anti-diabetes activity, anti-arthritis activity, hepatoprotective activity and antiasthmatic activity of galangin were discussed, and the related mechanisms were classified and summarized in detail. In addition, the drug combination, pharmacokinetics, drug delivery system and safety of galangin were furtherly discussed. CONCLUSIONS: This review will provide reference for galangin in the treatment of age-related diseases. Meanwhile, further experimental research and long-term clinical trials are needed to determine the therapeutic safety and efficacy of galangin.

Hyperoside attenuates pyrrolizidine alkaloids-induced liver injury by ameliorating TFEB-mediated mitochondrial dysfunction.

Pyrrolizidine alkaloids (PAs) are potent hepatotoxins that can cause liver damage. Hyperoside (Hyp), a natural flavonoid, can be extracted from medicinal plants. Hyp displays hepatoprotective activity in various liver diseases. However, the potential effect and mechanism of action of Hyp in ameliorating PA-induced liver injury remain obscure. This study aimed to explore the protective effect of Hyp against PA-induced hepatotoxicity and its underlying mechanism. We established an in vitro model of PAs in mouse primary hepatocytes and developed a mouse model of acute PA toxicity to investigate the protective effect of Hyp. We found that Hyp notably attenuated PA-induced hepatotoxicity. RNA-sequencing showed that the beneficial effect of Hyp against PA-induced hepatotoxicity was associated with the transcription factor EB (TFEB)-peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC1α) pathway. Our results confirmed that both the autophagy-lysosomal pathway and mitochondrial biogenesis were induced by Hyp through TFEB nuclear translocation in PA-induced liver injury. Furthermore, we demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) by MHY 1485 decreased TFEB nuclear translocation and abrogated the protective effect of Hyp against PA-induced liver injury in mice. In contrast, inhibition of mTORC1 activity increased the level of TFEB and reduced hepatotoxicity induced by PAs in mouse livers. Likewise, Hyp-induced TFEB activation was validated in vitro. In conclusion, Hyp can activate the TFEB-mediated autophagy-lysosomal pathway and mitochondrial biogenesis through inhibition of mTORC1 activity, alleviating the liver injury induced by PAs, thus suggesting the potential value of Hyp in the treatment of PA-induced hepatotoxicity.

Oligomeric phloroglucinols with hAChE inhibitory and antibacterial activities from tropic Rhodomyrtus tomentosa.

Alzheimer's diseases (AD) and other infectious diseases caused by drug-resistance bacteria have posed a serious threat to human lives and global health. With the aim to search for human acetylcholinesterase (hAChE) inhibitors and antibacterial agents from medicinal plants, 16 phloroglucinol oligomers, including two new phloroglucinol monomers (1a and 1b), four new phloroglucinol dimers (3a, 3b, 4b, and 5a), six new phloroglucinol trimers (6a, 6b, 7a, 7b, 8a, and 8b), and two naturally occurring phloroglucinol monomers (2a and 2b), along with two known congeners (4a and 5b), were purified from the leaves of tropic Rhodomyrtus tomentosa. The structures and absolute configurations of these new isolates were unequivocally established by comprehensive analyses of their spectroscopic data (NMR and HRESIMS), ECD calculation, and single crystal X-ray diffraction. Structurally, 3a/3b shared a rare C-5' formyl group, whereas 6a/6b possessed a unique C-7' aromatic ring. In addition, 7a/7b and 8a/8b were rare phloroglucinol trimers with a bis-furan and a C-6' hemiketal group. Pharmacologically, the mixture of 3a and 3b showed the most potent human acetylcholinesterase (hAChE) inhibitory activity with an IC50 value of 1.21 ± 0.16 µM. The molecular docking studies of 3a and 3b in the hAChE binding sites were performed, displaying good agreement with the in vitro inhibitory effects. In addition, the mixture of 3a and 3b displayed the most significant anti-MRSA (methicillin-resistant Staphylococcus aureus) with MIC and MBC values of both 0.50 µg/mL, and scanning electron microscope (SEM) studies revealed that they could destroy the biofilm structures of MRSA. The findings provide potential candidates for the further development of anti-AD and anti-bacterial agents.

Natural variation of MS2 confers male fertility and drives hybrid breeding in soybean.

A complete and genetically stable male sterile line with high outcrossing rate is a prerequisite for the development of commercial hybrid soybean. It was reported in the last century that the soybean male sterile ms2 mutant has the highest record with seed set. Here we report the cloning and characterization of the MS2 gene in soybean, which encodes a protein that is specifically expressed in the anther. MS2 functions in the tapetum and microspore by directly regulating genes involved in the biosynthesis of secondary metabolites and the lipid metabolism, which is essential for the formation of microspore cell wall. Through comparison of the field performance with the widely used male sterile mutants in the same genetic background, we demonstrated that the ms2 mutant conducts the best in outcrossing rate and makes it an ideal tool in building a cost-effective hybrid system for soybean.

Dietary Eicosapentaenoic Acid Containing Phosphoethanolamine Plasmalogens Remodels the Lipidome of White Adipose Tissue and Suppresses High-Fat Diet Induced Obesity in Mice.

SCOPE: Dietary supplementation of docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) can alter the lipidome profiles of adipocytes, thereby counteract obesity. DHA/EPA in the form of phospholipids demonstrates higher bioavailability than triglyceride or ethyl ester (EE), but their effects on the lipidome and metabolic changes during obesity are still unknown. METHODS AND RESULTS: High-fat diet-induced obese mice are treated with different molecular forms of EPA, and EPA supplemented as phosphoethanolamine plasmalogens (PlsEtn) has a superior effect on reducing fat mass accumulation than phosphatidylcholine (PC) or EE. The lipidomics analysis indicates that EPA in form of PlsEtn but not PC or EE significantly decreases total PC and sphingomyelin content in white adipose tissue (WAT). Some specific polyunsaturated fatty acid -containing PCs and ether phospholipids are increased in EPA-PlsEtn-fed mice, which may attribute to the upregulation of unsaturated fatty acid biosynthesis and fatty acid elongation reactions in WAT. In addition, the expression of genes related to fatty acid catabolism is also promoted by EPA-PlsEtn supplementation, which may cause the decreased content of saturated and monounsaturated fatty acid-containing PCs. CONCLUSIONS: EPA-PlsEtn supplementation is demonstrated to remodel lipidome and regulate the fatty acid metabolic process in WAT, indicating it may serve as a new strategy for obesity treatment in the future.

Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity.

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-ß-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

Alkaloids from Piper longum Exhibit Anti-inflammatory Activity and Synergistic Effects with Chemotherapeutic Agents against Cervical Cancer Cells.

Piper longum L. is widely cultivated for food, medicine, and other purposes in tropical and subtropical regions. Sixteen compounds including nine new amide alkaloids were isolated from the roots of P. longum. The structures of these compounds were determined by spectroscopic data. All compounds showed better anti-inflammatory activities (IC50 = 1.90 ± 0.68-40.22 ± 0.45 µM) compared to indomethacin (IC50 = 52.88 ± 3.56 µM). Among the isolated compounds, five dimeric amide alkaloids exhibited synergistic effects with three chemotherapeutic drugs (paclitaxel, adriamycin, or vincristine) against cervical cancer cells. Moreover, these dimeric amide alkaloids also enhanced the efficacy of paclitaxel in paclitaxel-resistant cervical cancer cells. The combination treatment of one of these dimeric amide alkaloids and paclitaxel promoted cancer cell apoptosis, which is related to the Src/ERK/STAT3 signaling pathway.

Vaginal Epithelial Cell Membrane-Based Phototherapeutic Decoy Confers a "Three-in-One" Strategy to Treat against Intravaginal Infection of Candida albicans.

Phototherapy is an effective strategy to control Candida albicans (C. albicans) infection without raising the concern of drug resistance. Despite its effectiveness, a higher dose of phototherapeutic power is required for C. albicans elimination compared to bacteria that have to be used, which is readily accompanied by off-target heat and toxic singlet oxygen to damage normal cells, thus limiting its usefulness for antifungal applications. Here to overcome this, we develop a "three-in-one" biomimetic nanoplatform consisting of an oxygen-dissolved perfluorocarbon camouflaged by a photosensitizer-loaded vaginal epithelial cell membrane. With a cell membrane coating, the nanoplatform is capable of specifically binding with C. albicans at the superficial or deep vaginal epithelium, thereby centering the phototherapeutic agents on C. albicans. Meanwhile, the cell membrane coating endows the nanoplatform to competitively protect healthy cells from candidalysin-medicated cytotoxicity. Upon candidalysin sequestration, pore-forming on the surface of the nanoplatform accelerates release of the preloaded photosensitizer and oxygen, resulting in enhanced phototherapeutic power for improved anti-C. albicans efficacy under near-infrared irradiation. In an intravaginal C. albicans-infected murine model, treatment with the nanoplatform leads to a significantly decreased C. albicans burden, particularly when leveraging candidalysin for further elevated phototherapy and C. albicans inhibition. Also, the same trends hold true when using the nanoplatform to treat the clinical C. albicans isolates. Overall, this biomimetic nanoplatform can target and bind with C. albicans and simultaneously neutralize the candidalysin and then transform such toxins that are always considered a positive part in driving C. albicans infection with the power of enhancing phototherapy for improved anti-C. albicans efficacy.