Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Research on Hydrogen-Induced Induced Cracking Sensitivity of X80 Pipeline Steel under Different Heat Treatments.

X80 pipeline steel has played a vital role in oil and gas transportation in recent years. However, hydrogen-related issues frequently lead to pipeline failures during service, resulting in significant losses of properties and lives. Three heat treatment processes (furnace cooling (FC), air cooling (AC), and water cooling (WC)) were carried out to investigate the effect of different microstructures on hydrogen-induced cracking (HIC) susceptibility of X80 pipeline steel. The WC sample demonstrated the highest hydrogen embrittlement index, registering at 21.9%, while the AC and FC samples exhibited progressively lower values of 15.45% and 10.98%, respectively. Under equivalent hydrogen charging durations, crack dimensions with a maximum length exceeding 30 µm in the WC sample generally exceed those in the FC sample and AC sample. The variation is attributed to the difference in microstructures of the samples, predominantly lath bainite (LB) in water-cooled samples, granular bainite (GB) in air-cooled samples, and ferrite/pearlite (F/P) in FC samples. The research results demonstrate that the sensitivity of lath bainite (LB) to HIC is significantly higher than that of pearlite, ferrite, and granular bainite (GB). The presence of a large amount of martensite/austenite (M/A) constituents within bainite results in a multitude of hydrogen trap sites. HIC cracks in bainite generally propagate along the profiles of M/A constituents, showing both intergranular and transgranular cracking modes.

Structural clarification of mannoglucan GSBP-2 from Ganoderma sinense and its effects on triple-negative breast cancer migration and invasion.

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, ß-d-Glcp-(1→, ß-d-GlcpA-(1→, →3)-ß-d-Glcp-(1→, →3)-ß-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-ß-d-Manp-(1→, and →3,6)-ß-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial-mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.

PD-1 inhibitors in advanced esophageal squamous cell carcinoma: a survival analysis of reconstructed patient-level data.

Background: Recently, a sum of trials of programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have shown excellent efficacy compared to chemotherapy alone in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no head-to-head comparison and consensus on which immunotherapy regimen results in better survival outcomes. This study aimed to evaluate the survival efficacy of various PD-1 inhibitor-based therapies in the first-line treatments for patients with advanced ESCC. Methods: Data collected prior to 31 July 2023 were searched in the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases. Overall survival (OS) and progression-free survival curves were pooled using the MetaSurv package. Survival data were compared by reconstructed individual patient data. Results: A total of 4,162 patients and seven randomized controlled trials were included. After synthesizing, PD-1 inhibitors prolonged median OS from 11.3 months (95% CI (confidence interval) 10.7-11.7) to 15.6 months (95% CI 14.7-16.3). Based on reconstructed patient-level data, the toripalimab, tislelizumab, and sintilimab group achieved the longest OS, whereas the sintilimab and tislelizumab group had the lowest risk of recurrence than other treatments. In patients with a combined positive score of ≥10, sintilimab had better OS efficacy than pembrolizumab (HR: 0.71, 95% CI: 0.52-0.96). In terms of tumor proportion score of ≥1%, camrelizumab, nivolumab, and toripalimab showed proximate survival benefits in both OS and progression-free survival. Conclusion: PD-1 inhibitor combined with chemotherapy significantly improved the survival time of patients with advanced ESCC. Toripalimab, tislelizumab, and sintilimab plus chemotherapy showed the best OS benefit. Longer progression-free benefits might be generated from adding tislelizumab and sintilimab to chemotherapy. Sintilimab was strongly recommended for patients with high programmed cell death-ligand 1 abundance. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42024501086].

Structural characterization of a galactoglucomannan with anti-neuroinflammatory activity from Ganoderma lucidum.

According to traditional Chinese medicine theory, Ganoderma lucidum (G. lucidum) presents certain effects for nourishing nerves and calming the mind. G. lucidum polysaccharides (GLPs) have various biological activities; however, the structural characterization and the structure-activity relationship in anti-neuroinflammation of GLPs needs to be further investigated. In this work, the crude polysaccharide GL70 exhibited a remarkable impact on enhancing the spatial learning and memory function, as well as reducing the anxiety symptoms of the lipopolysaccharide (LPS)-induced rat model of Alzheimer's disease (AD). A galactoglucomannan (GLP70-1-2) was isolated from GL70, and characterized by monosaccharide composition, partial acid hydrolysis, methylation, and NMR analysis. The backbone of GLP70-1-2 was →6)-α-D-glcp-(1 â†’ 6)-ß-D-galp-(1 â†’ [6)-ß-D-manp-(1]3 â†’ 4)-α-D-Glcp-(1 â†’ 6)-α-D-glcp-(1 â†’ 2)-ß-D-galp-(1 â†’ [4)-α-D-glcp-(1 â†’ 6)-ß-D-manp-(1 â†’ 2)-ß-D-galp-(1]2 â†’ 6)-ß-D-glcp-(1 â†’ 6)-ß-D-glcp-(1→ with two side chains attached to O-4 of →6)-ß-D-galp-(1→ and O-3 of →6)-ß-D-glcp-(1→, respectively. In addition, GLP70-1-2 exhibited remarkable efficacy in decreasing the level of pro-inflammatory factors in LPS-activated BV2 cells through the TLR4/MyD88/NF-κB pathway. Collectively, GLP70-1-2 exhibited significant anti-neuroinflammatory activity and may have the potential for developing as a drug for AD.

Structural identification and anti-neuroinflammatory effect of a heteropolysaccharide ATP50-3 from Acorus tatarinowii rhizome.

Acorus tatarinowii, a famous traditional Chinese medicine, is used for the clinical treatment of memory impairment and dementia. In this research, AT50, the crude polysaccharide extracted from A. tatarinowii rhizome, significantly improved the memory and learning ability of mice with Alzheimer's disease (AD) and exerted excellent anti-neuroinflammatory effects. More importantly, AT50 returned the levels of NO, TNF-α, IL-1ß, PGE-2, and IL-6 in AD mouse brains to normal levels. To identify the active ingredients in AT50, a heteropolysaccharide ATP50-3 was obtained from AT50. Structural analysis indicated ATP50-3 consisted of α-L-Araf-(1→, →2)-α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, α-D-Xylp-(1→, →3,4)-ß-D-Xylp-(1→, →3)-α-D-Galp-(1→, →3,6)-α-D-Galp-(1→, →6)-4-OAc-α-D-Galp-(1→, →3,4,6)-α-D-Galp-(1→, →4)-α-D-Glcp-(1→, →2,3,6)-ß-D-Glcp-(1→, →4,6)-α-D-Manp-(1→, →3,4)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→, and →4)-α-D-GlcpA-(1 â†’ residues and terminated with Xyl and Ara. Additionally, ATP50-3 significantly inhibited the release of proinflammatory factors in lipopolysaccharide-stimulated BV2 cells. ATP50-3 may be an active constituent of AT50, responsible for its anti-neuroinflammatory effects, with great potential to treat AD.

An arabinoxylan (AOP70-1) isolated from Alpinia oxyphylla alleviates neuroinflammation and neurotoxicity by TLR4/MyD88/NF-κB pathway.

Alpinia oxyphylla is famous for its neuroprotective and memory-improving effects. A crude polysaccharide AO70 from A. oxyphylla remarkably ameliorated neuroinflammation and cognitive dysfunction in Alzheimer's disease mice. This study aimed to explore the bioactive component of AO70 and its mechanism of action. A homogeneous polysaccharide (AOP70-1) rich in arabinose and xylose was purified from AO70, which was consisted of α-L-Araf-(1→, →5)-α-L-Araf-(1→, ß-D-Xylp-(1→,→2,4)-ß-D-Xylp-(1→, →2,3,4)-ß-D-Xylp-(1→, α-L-Rhap-(1→, α-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-α-D-GlcpA-(1→, ß-D-Galp-(1→, →2)-α-D-Galp-(1→, →6)-α-D-Galp-(1 â†’ and →3,6)-α-D-Manp-(1 →. AOP70-1 (2.5, 5, 10 µM) significantly suppressed NO, IL-1ß, and TNF-α production in a concentration-dependent manner and inhibited the migration of BV2 microglia. AOP70-1 inhibited LPS-mediated activation of Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein (MyD88), and nuclear factor kappa B (NF-κB). Moreover, AOP70-1 exerted neuroprotection on SH-SY5Y cells and primary neurons by reducing neuronal apoptosis (72 %, 44 %), alleviating ROS accumulation (63 %, 55 %), and improving mitochondrial membrane potential (63 %, 77 %). Overall, AOP70-1 is one of the major bioactive components in AO70 from A. oxyphylla, which has great potential in the prevention and treatment of neuroinflammation.

The role and application of vesicles in triple-negative breast cancer: Opportunities and challenges.

Extracellular vesicles (EVs) carry DNA, RNA, protein, and other substances involved in intercellular crosstalk and can be used for the targeted delivery of drugs. Triple-negative breast cancer (TNBC) is rich in recurrent and metastatic disease and lacks therapeutic targets. Studies have proved the role of EVs in the different stages of the genesis and development of TNBC. Cancer cells actively secrete various biomolecules, which play a significant part establishing the tumor microenvironment via EVs. In this article, we describe the roles of EVs in the tumor immune microenvironment, metabolic microenvironment, and vascular remodeling, and summarize the application of EVs for objective delivery of chemotherapeutic drugs, immune antigens, and cancer vaccine adjuvants. EVs-based therapy may represent the next-generation tool for targeted drug delivery for the cure of a variety of diseases lacking effective drug treatment.