Salvage haploidentical transplantation for graft failure after first haploidentical allogeneic stem cell transplantation: an updated experience.

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

MB16 - (M = Sc, Y, La): Perfect Bowl-like Boron Clusters.

The introduction of transition-metal doping has engendered a remarkable array of unprecedented boron motifs characterized by distinctive geometries and bonding, particularly those heretofore unobserved in pure boron clusters. In this study, we present a perfect (no defects) boron framework manifesting an inherently high-symmetry, bowl-like architecture, denoted as MB16- (M = Sc, Y, La). In MB16-, the B16 is coordinated to M atoms along the C5v-symmetry axis. The bowl-shaped MB16- structure is predicted to be the lowest-energy structure with superior stability, owing to its concentric (2π+10π) dual π aromaticity. Notably, the C5v-symmetry bowl-like B16- is profoundly stabilized through the doping of an M atom, facilitated by strong d-pπ interactions between M and boron motifs, in conjunction with additional electrostatic stabilization by an electron transfer from M to the boron motifs. This concerted interplay of covalent and electrostatic interactions between M and bowl-like B16 renders MB16- a species of exceptional thermodynamic stability, thus making it a viable candidate for gas-phase experimental detection.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Decreasing the steroid rapidly may help to improve the clinical outcomes of patients with intestinal steroid-refractory acute graft-versus-host disease receiving basiliximab treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer.

OBJECTIVE: The effects of arsenic trioxide (As2O3) on hepatocellular carcinoma have been documented widely. Autophagy plays dual roles in the survival and death of cancer cells. Therefore, we investigated the exact role of autophagy in As2O3-induced apoptosis in liver cancer cells. METHODS: The viability of hepatoma cells was determined using the MTT assay with or without fetal bovine serum. The rate of apoptosis in liver cancer cells treated with As2O3 was evaluated using flow cytometry, Hoechst 33258 staining, and TUNEL assays. The rate of autophagy among liver cancer cells treated with As2O3 was detected using immunofluorescence, Western blot assay and transmission electron microscopy. RESULTS: Upon treatment with As2O3, the viability of HepG2 and SMMC-7721 cells was decreased in a time- and dose-dependent manner. The apoptosis rates of both liver cancer cell lines increased with the concentration of As2O3, as shown by flow cytometry. Apoptosis in liver cancer cells treated with As2O3 was also shown by the activation of the caspase cascade and the regulation of Bcl-2/Bax expression. Furthermore, As2O3 treatment induced autophagy in liver cancer cells; this finding was supported by Western blot, immunofluorescence of LC3-II and beclin 1, and transmission electron microscopy. In liver cancer cells, As2O3 inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway that plays a vital role in both apoptosis and autophagy. The PI3K activator SC-79 partially reversed As2O3-induced autophagy and apoptosis. Furthermore, inhibiting autophagy with 3-methyladenine partially reversed the negative effects of As2O3 on cell viability. Serum starvation increased autophagy and amplified the effect of As2O3 on cell death. CONCLUSION: As2O3 induces apoptosis and autophagy in liver cancer cells. Autophagy induced by As2O3 may have a proapoptotic effect that helps to reduce the viability of liver cancer cells. This study provides novel insights into the effects of As2O3 against liver cancer. Please cite this article as: Deng ZT, Liang SF, Huang GK, Wang YQ, Tu XY, Zhang YN, Li S, Liu T, Cheng BB. Autophagy plays a pro-apoptotic role in arsenic trioxide-induced cell death of liver cancer. J Integr Med. 2024; Epub ahead of print.

SERS-based microdevices for use as in vitro diagnostic biosensors.

Advances in surface-enhanced Raman scattering (SERS) detection have helped to overcome the limitations of traditional in vitro diagnostic methods, such as fluorescence and chemiluminescence, owing to its high sensitivity and multiplex detection capability. However, for the implementation of SERS detection technology in disease diagnosis, a SERS-based assay platform capable of analyzing clinical samples is essential. Moreover, infectious diseases like COVID-19 require the development of point-of-care (POC) diagnostic technologies that can rapidly and accurately determine infection status. As an effective assay platform, SERS-based bioassays utilize SERS nanotags labeled with protein or DNA receptors on Au or Ag nanoparticles, serving as highly sensitive optical probes. Additionally, a microdevice is necessary as an interface between the target biomolecules and SERS nanotags. This review aims to introduce various microdevices developed for SERS detection, available for POC diagnostics, including LFA strips, microfluidic chips, and microarray chips. Furthermore, the article presents research findings reported in the last 20 years for the SERS-based bioassay of various diseases, such as cancer, cardiovascular diseases, and infectious diseases. Finally, the prospects of SERS bioassays are discussed concerning the integration of SERS-based microdevices and portable Raman readers into POC systems, along with the utilization of artificial intelligence technology.

Meta-analysis of transjugular intrahepatic portosystemic shunt creation with intravascular ultrasound guidance.

PURPOSE: To conduct a meta-analysis to assess the efficacy of intravascular ultrasound (IVUS) during transjugular intrahepatic portosystemic shunt (TIPS) creation. METHODS: MEDLINE and Embase databases were queried until July 2022 for comparative studies reporting procedure metrics for TIPS creation with or without IVUS guidance. Meta-analysis was performed with random-effects modeling for total procedural time, time to portal venous access, fluoroscopy time, iodinated contrast volume use, air kerma, dose area product, and number of needle passes. Intraoperative procedure-related complications were also reviewed. RESULTS: Of 95 unique records initially identified, 6 were eligible for inclusion. A total of 194 and 240 patients underwent TIPS with and without IVUS guidance. Pooled analyses indicated that IVUS guidance was associated with reduced total procedure time (SMD -0.76 [95% CI -1.02, -0.50] P < 0.001), time to portal venous access (SMD -0.41 [95% CI -0.67, -0.15] P = 0.002), fluoroscopy time (SMD, -0.54 [95% CI -1.02, -0.07]; P = 0.002), contrast volume use (SMD, -0.89 [95% CI -1.16, -0.63]; P < 0.001), air kerma (SMD, -0.75 [95% CI -1.11, -0.38]; P < 0.001) and dose area product (SMD, -0.98 [95% CI -1.77, -0.20]; P = 0.013). 4.2 and 7.8 needle passes were required in the IVUS and non-IVUS group, respectively (SMD, -0.60 [95% CI -1.42, 0.21]; P = 0.134), whereas pooled complication rates were 15.2% (12/79), and 21.4% (28/131), respectively. CONCLUSION: IVUS guidance during TIPS creation improves procedural metrics including procedural time, contrast usage, and radiation exposure.

Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model.

Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.

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.

Effects of fluorene-9-bisphenol exposure on anxiety-like and social behavior in mice and protective potential of exogenous melatonin.

Fluorene-9-bisphenol (BHPF) is widely used in the manufacture of plastic products and potentially disrupts several physiological processes, but its biological effects on social behavior remain unknown. In this study, we investigated the effects of BHPF exposure on anxiety-like and social behavior in female mice and the potential mechanisms, thereby proposing a potential therapy strategy. We exposed female Balb/c mice to BHPF by oral gavage at different doses (0.5, 50 mg/kg bw/2-day) for 28 days, which were found BHPF (50 mg/kg) exposure affected motor activity in the open field test (OFT) and elevated cross maze (EPM), resulting in anxiety-like behaviors, as well as abnormal social behavioral deficits in the Social Interaction Test (SIT). Analysis of histopathological staining results showed that BHPF exposure caused damage to hippocampal neurons in the CA1/CA3/DG region and decreased Nissl pyramidal neurons in the CA1/CA3 regions of the hippocampus, as well as a decrease in parvalbumin neuron expression. In addition, BHPF exposure upregulated the expression of excitatory and inhibitory (E/I) vesicle transporter genes (Vglut1, Vglut2, VGAT, GAD67, Gabra) and axon growth gene (Dcc) in the mouse hippocampus. Interestingly, behavioral disturbances and E/I balance could be alleviated by exogenous melatonin (15 mg/kg bw/2-day) therapy. Our findings suggest that exogenous melatonin may be a potential therapy with protective potential for ameliorating or preventing BHPF-induced hippocampal neuronal damage and behavioral disturbances. This study provided new insight into the neurotoxicological effects on organisms exposed to endocrine-disrupting chemicals and aroused our vigilance in current environmental safety about chemical use.

Fabrication and Application of Ag@SiO2/Au Core-Shell SERS Composite in Detecting Cu2+ in Water Environment.

A sensitive and simple method for detecting Cu2+ in the water source was proposed by using surface-enhanced Raman scattering spectroscopy (SERS) based on the Ag@SiO2/Au core-shell composite. The Ag@SiO2 SERS tag was synthesized by a simple approach, in which Ag nanoparticles were first embedded with Raman reporter PATP and next coated with a SiO2 shell. The Ag@SiO2 nanoparticles had strong stability even in a high-concentration salty solution, and there were no changes to their properties and appearance within one month. The Ag@SiO2/Au composite was fabricated through a controllable self-assemble process. L-cysteine was decorated on the surface of a functionalized Ag@SiO2/Au composite, as the amino and carboxyl groups of it can form coordinate covalent bond with Cu2+, which shows that the Ag@SiO2/Au composite labelled with L-cysteine has excellent performance for the detection of Cu2+ in aqueous media. In this study, the SERS detection of Cu2+ was carried out using Ag@SiO2 nanoparticles, and the limit of detection (LOD) as low as 0.1 mg/L was achieved.

Chromosomal integration and plasmid fusion occurring in ST20 carbapenem-resistant Klebsiella pneumoniae isolates coharboring blaNDM-1 and blaIMP-4 induce resistance transmission and fitness variation.

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-ß-lactamases (MBL)-harbouring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harbouring plasmid contributed to the increased resistance to ß-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harbouring isolates, should be given additional attention.

Magnetostrictive-piezocatalytic CoFe2O4@UiO-66 nanohybrid and its potential for deep-seated tumor treatment.

Magnetostrictive CoFe2O4 (CFO) nanoparticles were encapsulated within a UiO-66 metal-organic-framework layer to form a CFO@UiO-66 nanohybrid. The deforming of CFO, in response to a high-frequency AC magnetic field, initiates the piezocatalytic property of UiO-66 to generate ˙OH radicals, which can kill cancer cells buried in thick tissues, showcasing bright potential for deep-seated tumor treatment.

Sand cat swarm optimization algorithm and its application integrating elite decentralization and crossbar strategy.

Sand cat swarm optimization algorithm is a meta-heuristic algorithm created to replicate the hunting behavior observed by sand cats. The presented sand cat swarm optimization method (CWXSCSO) addresses the issues of low convergence precision and local optimality in the standard sand cat swarm optimization algorithm. It accomplished this through the utilization of elite decentralization and a crossbar approach. To begin with, a novel dynamic exponential factor is introduced. Furthermore, throughout the developmental phase, the approach of elite decentralization is incorporated to augment the capacity to transcend the confines of the local optimal. Ultimately, the crossover technique is employed to produce novel solutions and augment the algorithm's capacity to emerge from local space. The techniques were evaluated by performing a comparison with 15 benchmark functions. The CWXSCSO algorithm was compared with six advanced upgraded algorithms using CEC2019 and CEC2021. Statistical analysis, convergence analysis, and complexity analysis use statistics for assessing it. The CWXSCSO is employed to verify its efficacy in solving engineering difficulties by handling six traditional engineering optimization problems. The results demonstrate that the upgraded sand cat swarm optimization algorithm exhibits higher global optimization capability and demonstrates proficiency in dealing with real-world optimization applications.

Pan­immune­inflammation value as a novel prognostic biomarker in nasopharyngeal carcinoma.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

Multiple Bonding in AeN- (Ae = Ca, Sr, Ba).

Quantum chemical calculations using ab initio methods at the MRCI+Q(8,9)/def2-QZVPPD and CCSD(T)/def2-QZVPPD levels as well as density functional theory are reported for the diatomic molecules AeN- (Ae = Ca, Sr, Ba). The nature of the bonds is analyzed with a variety of methods. The anions CaN- and SrN- have electronic triplet (3Π) ground states with nearly identical bond dissociation energies De ~57 kcal/mol calculated at the MRCI+Q(8,9)/def2-QZVPPD level of theory. In contrast, the heavier homologue BaN- has a singlet (1Σ+) ground state, which is only 1.1 kcal/mol below the triplet (3Σ-) state. The computed bond dissociation energy of (1Σ+) BaN- is 68.4 kcal/mol. The calculations at the CCSD(T)-full/def2-QZVPPD and BP86-D3(BJ)/def2-QZVPPD levels of theory are in reasonable agreement with the MRCI+Q(8,9)/def2-QZVPPD data except for the singlet (1Σ+) state, which has a large multireference character. The calculated atomic partial charges given by the CM5, Voronoi and Hirshfeld methods suggest small to medium-sized charge donation toward Ae atom Ae←N- for most electronic states. In contrast, the NBO method predicts for all species medium to large electronic charge donation toward nitrogen Ae→N-, which is due to the neglect of the (n)p AOs of Ae atoms as genuine valence orbitals.

Expression landscape of cancer-FOXP3 and its prognostic value in pancreatic adenocarcinoma.

FOXP3, a key identifier of Treg, has also been identified in tumor cells, which is referred to as cancer-FOXP3 (c-FOXP3). Human c-FOXP3 undergoes multiple alternative splicing events, generating several isoforms, like c-FOXP3FL and c-FOXP3Δ3. Previous research on c-FOXP3 often ignore its cellular source (immune or tumor cells) and isoform expression patterns, which may obscure our understanding of its clinical significance. Our immunohistochemistry investigations which conducted across 18 tumors using validated c-FOXP3 antibodies revealed distinct expression landscapes for c-FOXP3 and its variants, with the majority of tumors exhibited a predominantly expression of c-FOXP3Δ3. In pancreatic ductal adenocarcinoma (PDAC), we further discovered a potential link between nuclear c-FOXP3Δ3 in tumor cells and poor prognosis. Overexpression of c-FOXP3Δ3 in tumor cells was associated with metastasis. This work elucidates the expression pattern of c-FOXP3 in pan-cancer and indicates its potential as a prognostic biomarker in clinical settings, offering new perspectives for its clinical application.

Construction of cyclobutane-fused tetracyclic skeletons via substrate-dependent EnT-enabled dearomative [2+2] cycloaddition of benzofurans (benzothiophenes)/maleimides.

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.

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, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2, nitric oxide synthase, TNF-α, IL-6, and interleukin-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.