An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome.

Inulin-type fructan CP-A, a predominant polysaccharide in Codonopsis pilosula, demonstrates regulatory effects on immune activity and anti-inflammation. The efficacy of CP-A in treating ulcerative colitis (UC) is, however, not well-established. This study employed an in vitro lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) and an in vivo dextran sulfate sodium (DSS)-induced colitis mouse model to explore CP-A's protective effects against experimental colitis and its underlying mechanisms. We monitored the clinical symptoms in mice using various parameters: body weight, disease activity index (DAI), colon length, spleen weight, and histopathological scores. Additionally, molecular markers were assessed through enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays. Results showed that CP-A significantly reduced reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6, IL-1ß, IL-18) in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1, ZO-1, and occludin proteins in NCM460 cells. Correspondingly, in vivo findings revealed that CP-A administration markedly improved DAI, reduced colon shortening, and decreased the production of myeloperoxidase (MPO), malondialdehyde (MDA), ROS, IL-1ß, IL-18, and NOD-like receptor protein 3 (NLRP3) inflammasome-associated genes/proteins in UC mice. CP-A treatment also elevated glutathione (GSH) and superoxide dismutase (SOD) levels, stimulated autophagy (LC3B, P62, Beclin-1, and ATG5), and reinforced Claudin-1 and ZO-1 expression, thereby aiding in intestinal epithelial barrier repair in colitis mice. Notably, the inhibition of autophagy via chloroquine (CQ) diminished CP-A's protective impact against colitis in vivo. These findings elucidate that CP-A's therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagy-mediated NLRP3 inflammasome inactivation. Consequently, inulin-type fructan CP-A emerges as a promising drug candidate for UC treatment.

Instant and short-term effects of acupuncture for depression and anxiety in unstable angina pectoris patients with percutaneous coronary interventions.

Aim: Patients with unstable angina pectoris (UAP) usually present anxiety or depression during percutaneous coronary intervention (PCI). This study sought to investigate the instant and short-term effects of acupuncture for anxiety and depression in UAP patients with PCI. Methods: A total of 210 UAP patients who underwent PCI were recruited and randomly assigned (1:1:1) to acupuncture, placebo, or control groups. Enzyme-linked immunosorbent assay was used to detect the levels of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (Hs-CRP), advanced oxidation protein products (AoPPs), and oxidized low-density lipoprotein (OX-LDL). Serial questionnaires with the Hamilton Anxiety (HAMA) scale and the Pittsburgh Sleep Quality Index were evaluated, and heart rate variability indicators were obtained. Results: Primary end-point: low frequency/high frequency (HF) was lower in the electroacupuncture group (p = 0.014), while standard deviation of normal-to-normal intervals, average standard deviation of normal-to-normal intervals, percentage of successive intervals that differ more than 50 ms, and HF were increased with acupuncture (p = 0.018, p = 0.043, p = 0.016, and p = 0.002, respectively). Secondary end-point: significant improvements in anxiety levels (HAMA) were observed in the three groups (p < 0.001). The fasting insulin and HOMA-IR levels were similar between the control group and the acupuncture group (p = 0.285 and p = 0.165, respectively). The levels of IL-6 and AoPPs differed among the three groups (p = 0.021 and p < 0.001, respectively). However, no significant differences were found in fasting plasma glucose, fasting c-peptide, Hs-CRP, and OX-LDL levels among the three groups (p = 0.585, p = 0.611, p = 0.902, and p = 0.756, respectively). Conclusions: In this study, short-term acupuncture may potentially relieve clinical symptoms before PCI treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT03789344).

Adsorption performance of ammonium molybdate modified Salix wood flour biochar for the treatment of monosodium glutamate wastewater.

ABSTRACTThe problem of wastewater pollution in the production of monosodium glutamate (MSG) is becoming more and more serious. A novel type of chemically modified Salix psammophila powder charcoal (SPPCAM) was synthesized to address the chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) in MSG wastewater. SPPCAM was prepared by carbonization method, in which inorganic ammonium molybdate (AM) was used as modifier and Salix psammophila powder (SPP) was used as raw material. Under optimal treatment conditions, maximum removal rates (removal capacities) of 45.9% (3313.2 mg·L-1) for COD and 29.4% (23.2 mg·L-1) for NH3-N in MSG wastewater were achieved. The treatment results significantly outperforming the unmodified Salix psammophila powder charcoal (SPPC), which only achieved removal rates (removal capacities) of 10.6% (763.9 mg·L-1) for COD and 12.9% (10 mg·L-1) for NH3-N. SPPC and SPPCAM before and after preparation were analysed by FT-IR and XRD, and Mo ions in the form of Mo2C within SPPCAM were successfully loaded. SEM, EDS-Mapping, BET, and other methods were used to analyse SPPCAM before and after MSG wastewater treatment, demonstrating that SPPCAM effectively treated organic pollutants in monosodium glutamate wastewater. The NH3-N in the treated MSG wastewater has reached the standard of safe discharge.

A Pectate Lyase Gene Plays a Critical Role in Xylem Vascular Development in Arabidopsis.

As a major component of the plant primary cell wall, structure changes in pectin may affect the formation of the secondary cell wall and lead to serious consequences on plant growth and development. Pectin-modifying enzymes including pectate lyase-like proteins (PLLs) participate in the remodeling of pectin during organogenesis, especially during fruit ripening. In this study, we used Arabidopsis as a model system to identify critical PLL genes that are of particular importance for vascular development. Four PLL genes, named AtPLL15, AtPLL16, AtPLL19, and AtPLL26, were identified for xylem-specific expression. A knock-out T-DNA mutant of AtPLL16 displayed an increased amount of pectin, soluble sugar, and acid-soluble lignin (ASL). Interestingly, the atpll16 mutant exhibited an irregular xylem phenotype, accompanied by disordered xylem ray cells and an absence of interfascicular phloem fibers. The xylem fiber cell walls in the atpll16 mutant were thicker than those of the wild type. On the contrary, AtPLL16 overexpression resulted in expansion of the phloem and a dramatic change in the xylem-to-phloem ratios. Altogether, our data suggest that AtPLL16 as a pectate lyase plays an important role during vascular development in Arabidopsis.

[Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke].

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION: Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Therapeutic effects and mechanisms of Ku-Gan formula on atopic dermatitis: A pilot clinical study and modular pharmacology analysis with animal validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a persistent, recurrent inflammatory skin disorder with a rapid upward trend worldwide. The first-line treatment for AD consists of topical medicines such as topical corticosteroids (TCSs). However, long-term use of conventional topical medicine results in side effects and recurrence, presenting therapeutic challenges for the management of AD. Ku-Gan formula (KG) has been extensively used to treat skin diseases since the Song dynasty. In particular, topical administration of the KG alleviates the cutaneous symptoms of AD and reduces recurrence rates with a good safety profile; however, the mechanisms of the KG's action remain unknown. AIM OF THE STUDY: The current study aimed to evaluate the efficacy and safety of KG in AD patients and to investigate the molecular mechanisms that underlie the efficacy of KG in the treatment of AD. MATERIALS AND METHODS: A single-arm prospective pilot study with historical controls was conducted. This study evaluated 11 patients with mild to moderate AD, who underwent topical KG treatment. The primary outcome was the change in local eczema area and severity index (EASI) scores. The secondary outcomes included the recurrence rate and safety. The recurrence rate were compared to those of a matched historical control group. Secondly, modular pharmacology analysis was used to elucidate the therapeutic mechanism of KG in AD treatment by identifying the hub genes and kernel pathways. Moreover, we evaluated treatment effects and verified modular pharmacology-based findings using the calcipotriol (MC903)-induced mouse model and bioinformatics analysis. RESULTS: Our clinical pilot study demonstrated that the KG wet wrapping could effectively ameliorate skin lesions in AD patients with a significant drop from 4.18 to 1.63 in local EASI. Compared to the historical controls, KG had a reduced recurrence rate (36%) and a longer median time to relapse (>12 weeks). Modular pharmacology analysis identified the hub genes including IL6, IL1B, VEGFA, STAT3, JUN, TIMP1 and ARG1, and kernel pathway including IL-17 signaling pathway of KG. Pharmacodynamic results suggested that KG ameliorated skin symptoms and demonstrated no less efficacy than halcinonide (HC) in MC903-induced AD-like mice. In addition, KG regulated the mRNA expression of hub genes as well as the related genes involved in IL-17 signaling pathway including Il25, Il17a,Traf3ip2, and Traf6, in skin lesions of AD-like mice. CONCLUSION: These results showed that KG is a safe and effective topical treatment for AD with low recurrence. In addition, our study identified potential molecular pathways and therapeutic candidate targets of the KG formula, providing evidence for its clinical applicability in AD.

Microwave-assisted enzymatic extraction brings a notably high yield of polysaccharides from mountain Zizania latifolia.

Mountain Zizania latifolia is produced at scale in China, and the edible swollen culm is exported to many countries, but little attention has been paid to its functional components. In this work, microwave-assisted enzymatic extraction (MAEE) is used for the first time to extract polysaccharides from mountain Z. latifolia swollen culm (PMZL). MAEE conditions optimized by Box-Behnken design-response surface methodology were as follows: 2.4% cellulase, microwaving for 6.0 min at 607 W, with a liquid-to-solid ratio of 63:1 ml g-1 . Under these conditions, a notably high yield of 60.43% ± 1.12% for PMZL was achieved, which was significantly higher (p < 0.01) than from plain-grown varieties. PMZL are naturally occurring sulfated polysaccharide-protein complexes containing 8.46% ± 0.18% proteins and 7.86% ± 0.73% sulfates. PMZL comprises mannose, glucosamine, rhamnose, glucose, galactose, and arabinose at molar ratios of 3.80:2.68:1.00:17.41:5.12:2.91, with a weight-average molecular weight of 1569,219 Da and a number-average molecular weight of 364,088 Da. The surface morphology of PMZL is composed of tightly packed oval particles, and this kind of promising polysaccharides preferentially scavenges reactive nitrogen species. PRACTICAL APPLICATION: Due to global warming, the land available for planting vegetables is likely to expand to higher areas, so greater attention should now be paid to mountain-grown vegetables. This study provides an efficient way to obtain novel polysaccharides from mountain Zizania latifolia using microwave-assisted enzymatic extraction with a remarkably high yield of 60.4%. This promising source of natural carbohydrates has potential uses in pharmaceutical, nutraceutical, functional foods, cosmetics, and functional materials industries.

Molecular Structure and Phylogenetic Analyses of the Complete Chloroplast Genomes of Three Medicinal Plants Conioselinum vaginatum, Ligusticum sinense, and Ligusticum jeholense.

Most plants of Ligusticum have an important medicinal and economic value with a long history, Ligusticum sinense and L. jeholense ("Gaoben") has long been used in traditional Chinese medicine for the treatment of carminative, dispelling cold, dehumidification, and analgesia. While in the market Conioselinum vaginatum (Xinjiang Gaoben) is substitution for Gaoben, and occupies a higher market share. These three Gaoben-related medicinal materials are similar in morphology, and are difficult to distinguish from each other by the commonly used DNA barcodes. The chloroplast genome has been widely used for molecular markers, evolutionary biology, and barcoding identification. In this study, the complete chloroplast genome sequences of C. vaginatum, L. sinense, and L. jeholense were reported. The results showed that the complete chloroplast genomes of these three species have typical quadripartite structures, which were comprised of 148,664, 148,539, and 148,497 bp. A total of 114 genes were identified, including 81 protein-coding genes (PCGs), 29 tRNA genes, and four rRNA genes. Our study indicated that highly variable region ycf2-trnL and accD-ycf4 that can be used as specific DNA barcodes to distinguish and identify C. vaginatum, L. sinense, and L. jeholense. In addition, phylogenetic study showed that C. vaginatum nested in Ligusticum and as a sister group of L. sinense and L. jeholense, which suggested these two genera are both in need of revision. This study offer valuable information for future research in the identification of Gaoben-related medicinal materials and will benefit for further phylogenetic study of Apiaceae.

Corrigendum to "Effects of Chicory on Serum Uric Acid, Renal Function, and GLUT9 Expression in Hyperuricaemic Rats with Renal Injury and In Vitro Verification with Cells".

[This corrects the article DOI: 10.1155/2018/1764212.].

Sulfidised nanoscale zerovalent iron-modified pitaya peel-derived carbon for enrofloxacin degradation and swine wastewater treatment: Combination of electro-Fenton and bio-electro-Fenton process.

In this study, a new Fenton system combining electro-Fenton and bio-electro-Fenton (EF-BEF) processes was proposed for ENR degradation and swine wastewater treatment, and pitaya peel-derived carbon modified with sulfidised nanoscale zerovalent iron (SnZVI) was developed as a catalyst for the system. The as-prepared PPC-800 carbon displayed a hierarchical porous structure (693.5 m2/g), abundant oxygen-containing groups, and carbon defects, which endowed it with a good adsorption capacity, high H2O2 generation capacity (151.9 ± 10.5 mg/L) during the EF period, and good power production performance (194.3 ± 12.50 mW/m2) during the BEF period. When modified with SnZVI, despite the decrease in the adsorption capacity and power output (102.05 ± 4.05 mW/m2), the SnZVI@PPC-2 exhibited the best ENR removal performance with that of 98.9 ± 0.2% in the EF period and 86.2 ± 5.6% during the BEF period. An increase in the current intensity and air flow rate promoted ENR degradation. Finally, swine wastewater was treated using the SnZVI@PPC-2 EF-BEF system, and 97.9 ± 1.3% of the TOC was removed using the combined system.

Immunosuppressive effect of Columbianadin on maturation, migration, allogenic T cell stimulation and phagocytosis capacity of TNF-α induced dendritic cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelicae pubescentis radix (APR) has a long history in the treatment of rheumatoid arthritis (RA) in China. It has the effects of dispelling wind to eliminate dampness, removing arthralgia and stopping pain in the Chinese Pharmacopeia, but its mechanisms was unclear. Columbianadin (CBN) was one of the main bioactive compounds of APR, and has many pharmacological effects. But the immunosuppressive effect of CBN on DCs and the potential mechanism needed to be explored. AIM OF THE STUDY: The study was aimed to clarify the immunosuppressive effect of CBN on maturation, migration, allogenic T cell stimulation and phagocytosis capacity of TNF-α induced DCs. MATERIALS AND METHODS: Bone marrow-derived DCs were obtained and cultured from C57BL/6 mice in accordance with protocol. The phenotypic study (CD11c, CD40, CD80, CD86 and MHC Ⅱ) were measured by flow cytometry. FITC-dextran were uptaked by DCs and the change of endocytosis activity were mediated by acquired mannose receptor. Transwell chambers were used to detect the migration ability of DCs. Mixed leukocyte reaction (MLR) assay was used to detect the allostimulatory ability of CBN on TNF-α stimulated DCs. The secretion of cytokines and chemokines was measured by ELISA Kit. TLRs gene and MAPKs/NF-κB protein expression were checked by qRT-PCR and Western blot. RESULTS: CBN inhibited the maturation of TNF-α-induced DCs while maintaining phagocytosis capabilities. Additionally, CBN inhibited the migration of TNF-α stimulated DCs, which related to reduce the production of chemokines (MCP-1, MIP-1α). Notably, CBN could suppress the proliferation of CD4+T cells by inhibiting DCs maturation, and decrease the proinflammatory cytokines IL-6 production. Furthermore, CBN inhibited mRNA expression of TLR2, TLR7 and TLR9 in TNF-α-activated DCs. Meanwhile, the phosphorylation of p38, JNK1/2 and NF-κB protein were significantly inhibited in CBN treated DCs. CONCLUSIONS: These findings provided novel insights into the pharmacological activity of CBN. They also indicated that inhibition DCs maturation owning to the immunosuppressive effect of CBN. CBN was expected as a potential immunosuppressant and TLRs/MAPKs/NF-κB pathway may be an important mechanism for CBN's immunosuppressive activity.

Zanthoxylum bungeanum Seed Oil Attenuates LPS-Induced BEAS-2B Cell Activation and Inflammation by Inhibiting the TLR4/MyD88/NF-κB Signaling Pathway.

BACKGROUND: Zanthoxylum bungeanum seed oil (ZBSO) is a natural essential oil derived from the seeds of the Chinese medicinal plant Zanthoxylum bungeanum, which has been investigated for antitumor and anti-inflammatory effects. However, little is known regarding the effects of ZBSO in chronic obstructive pulmonary disease (COPD). METHODS: In this study, lung epithelial cells (BEAS-2B) were induced by lipopolysaccharide (LPS) to establish an in vitro model of COPD, and cytotoxicity was detected by a cell counting kit 8 (CCK-8) assay. Griess test, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot, immunofluorescence, and molecular docking analyses were used to investigate the effects of ZBSO and its potential mechanisms. RESULTS: The results showed that LPS promoted the expression of nitric oxide (NO), reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), MMP-9, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2), suggesting that LPS can induce inflammation and oxidative stress in BEAS-2B cells. ZBSO inhibits the LPS-induced expression of inflammatory mediators and proinflammatory cytokines in BEAS-2B cells. The molecular docking results indicated that active components in ZBSO could successfully dock with toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and p65. Immunofluorescence and western blot analyses further demonstrated that ZBSO repressed protein expression associated with the TLR4/MyD88/nuclear factor-κB (NF-κB) signaling pathway. CONCLUSIONS: ZBSO reduced the inflammatory response and oxidative stress induced by LPS by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby suppressing COPD. ZBSO may represent a promising therapeutic candidate for COPD treatment.

Potent antiviral activity of Agrimonia pilosa, Galla rhois, and their components against SARS-CoV-2.

Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.

Zanthoxylum bungeanum Seed Oil Elicits Autophagy and Apoptosis in Human Laryngeal Tumor Cells via PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: Zanthoxylum bungeanum seed oil (ZBSO) is the main extract of the edible drug Zanthoxylum bungeanum seeds. Recent reports have proved that it has a significant cytotoxic effect on various cancer cells. However, systematic investigation on the role of ZBSO in laryngeal carcinoma (LC) is rare. OBJECTIVE: The aim of the study was to reveal the function of ZBSO on human laryngeal squamous carcinoma cells (Hep-2) and to elucidate its underlying mechanism. METHODS: In this study, the chemical composition analysis of ZBSO was done using Ultra Performance Liquid Chromatography (UPLC), and the anti-tumor effect of ZBSO on Hep-2 cells was evaluated by cell proliferation, apoptosis and cell cycle experiments. qRT-PCR, immunohistochemistry (IHC) and Western blotting were used for mechanistic investigation at the molecular level. RESULTS: The main compound of ZBSO was identified as polyunsaturated fatty acids. Furthermore, as compared to normal cells, significant inhibitory activities of ZBSO were observed on Hep-2 cells with dose- and timedependency, which induced apoptosis, blocked cell cycle at the S phase, and inhibited cell proliferation. In addition, IHC results showed a difference in the level of protein expression of ZBSO-induced autophagy-related markers. At last, Western blotting results indicated that ZBSO could inhibit the expression and phosphorylation levels of PI3K/AKT/mTOR protein. CONCLUSION: The anti-LC effect of ZBSO might be intimately associated with the induction of autophagy and the inhibition of the PI3K/AKT/mTOR signaling pathway. ZBSO may be a potential anti-laryngocarcinoma agent.

Establishing the Carbonation Profile with Raman Spectroscopy: Effects of Fly Ash and Ground Granulated Blast Furnace Slag.

Establishing the carbonation profile is of great significance to the prediction of the service life of reinforced concrete structures. In our previous work, Raman spectroscopy was shown to be an efficient tool for characterizing calcium carbonate (CaCO3) polymorphs and their profile in plain Portland cement (PC) matrices. However, as supplementary cementitious materials (SCMs), particularly fly ash (FA) and ground granulated blast furnace slag (GGBS), are widely used in concrete, establishing the carbonation profile without considering the possible effects of these SCMs could be of little significance to the real world. This paper, thus, investigated the effects of FA and GGBS on the working capacity and reliability of Raman spectroscopy for establishing the carbonation profile in PC blends containing SCMs. The thermogravimetry (TG) analysis was also conducted to verify the results from Raman spectroscopy. The results show that Raman spectroscopy demonstrated a good capacity for differentiating the variation of CaCO3 contents in FA or GGBS blends. However, the incorporation of FA and GGBS into the PC system caused some adverse effects on the quantification of CaCO3 by Raman spectroscopy, which could be attributed to the darker color and weak scatter nature of FA and the high content of glassy phases in GGBS.

Mn-containing bioceramics inhibit osteoclastogenesis and promote osteoporotic bone regeneration via scavenging ROS.

Osteoporosis is caused by an osteoclast activation mechanism. People suffering from osteoporosis are prone to bone defects. Increasing evidence indicates that scavenging reactive oxygen species (ROS) can inhibit receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and suppress ovariectomy-induced osteoporosis. It is critical to develop biomaterials with antioxidant properties to modulate osteoclast activity for treating osteoporotic bone defects. Previous studies have shown that manganese (Mn) can improve bone regeneration, and Mn supplementation may treat osteoporosis. However, the effect of Mn on osteoclasts and the role of Mn in osteoporotic bone defects remain unclear. In present research, a model bioceramic, Mn-contained ß-tricalcium phosphate (Mn-TCP) was prepared by introducing Mn into ß-TCP. The introduction of Mn into ß-TCP significantly improved the scavenging of oxygen radicals and nitrogen radicals, demonstrating that Mn-TCP bioceramics might have antioxidant properties. The in vitro and in vivo findings revealed that Mn2+ ions released from Mn-TCP bioceramics could distinctly inhibit the formation and function of osteoclasts, promote the differentiation of osteoblasts, and accelerate bone regeneration under osteoporotic conditions in vivo. Mechanistically, Mn-TCP bioceramics inhibited osteoclastogenesis and promoted the regeneration of osteoporotic bone defects by scavenging ROS via Nrf2 activation. These results suggest that Mn-containing bioceramics with osteoconductivity, ROS scavenging and bone resorption inhibition abilities may be an ideal biomaterial for the treatment of osteoporotic bone defect.

Population-Based Comparison of Different Risk Stratification Systems Among Prostate Cancer Patients.

BACKGROUND: It is not known which risk stratification system has the best discrimination ability for predicting prostate cancer death. METHODS: We identified patients with non-metastatic primary prostate adenocarcinoma diagnosis between 2004 and 2015 using the Surveillance, Epidemiology, and End Results database. Patients were categorized in different risk groups using the three frequently used risk stratification systems of the National Comprehensive Cancer Network guideline (NCCN-g), American Urological Association guideline (AUA-g), and European Association of Urology guideline (EAU-g), respectively. Associations between risk classification and prostate cancer-specific mortality (PCSM) were determined using Kaplan-Meier analyses and multivariable regression with Cox proportional hazards model. Area under the receiver operating characteristics curve (AUC) analyses were used to test the discrimination ability of the three risk grouping systems. RESULTS: We analyzed 310,062 patients with a median follow-up of 61 months. A total of 36,368 deaths occurred, including 6,033 prostate cancer deaths. For all the three risk stratification systems, the risk groups were significantly associated with PCSM. The AUC of the model relying on NCCN-g, AUA-g, and EAU-g risk stratification systems for PCSM at specifically 8 years were 0.818, 0.793, and 0.689 in the entire population; 0.819, 0.795, and 0.691 in Whites; 0.802, 0.777, and 0.681 in Blacks; 0.862, 0.818, and 0.714 in Asians; 0.845, 0.806, and 0.728 in Chinese patients. Regardless of the age, marital status, socioeconomic status, and treatment modality, AUC of the model relying on NCCN-g and AUA-g for PCSM was greater than that relying on EAU-g; AUC of the model relying on NCCN-g system was greater than that of the AUA-g system. CONCLUSIONS: The NCCN-g and AUA-g risk stratification systems perform better in discriminating PCSM compared to the EAU-g system. The discrimination ability of the NCCN-g system was better than that of the AUA-g system. It is recommended to use NCCN-g to evaluate risk groups for prostate cancer patients and then provide more appropriate corresponding treatment recommendations.

Progress in the Study of Epidemiologic Characteristics and Influencing Factors of Asymptomatic Malaria Infection in Africa.

Malaria is caused by protozoan parasitic Plasmodium infections. Plasmodium falciparum is common in Africa; P ovale, P malaria and P vivax infections are less prevalent and globally confined, contributing to major causes of global mortality and morbidity, particularly in children in sub-Saharan African countries. In 2018, the total incidence of malaria increased from 221 million to 229 million, with an estimated 503 000 deaths reported. Sub-Saharan Africa has the highest number of cases of malaria and highest mortality rate compared with other countries, like southeastern Asia, east Pacific, western, and America with an estimated 213 million cases. In addition, continuous exposure to Plasmodium parasites results in the production of partial immunity to guard against more problems, resulting in asymptomatic carriers. The diagnosis of asymptomatic malaria is not simple because of the apparent absence of clinical factors and sometimes low levels of parasites. The most basic concept appears to be parasitemia and a lack of malaria signs, primarily fever (axillary temperature <37.5° C). Thus, a better awareness of asymptomatic malaria epidemiology in affected countries will help improve strategies to reduce the local burden of malaria and its health consequences. Therefore, the objective of this study was to determine the magnitude of asymptomatic malaria pathology and related risk factors with epidemiologic characteristics in individuals on the African continent.

The Bariatric Experience Long Term (BELONG): Factors Related to Having Bariatric Surgery in a Large Integrated Healthcare System.

PURPOSE: Bariatric surgery is the most effective treatment for severe obesity, but currently, only 1-2% of all eligible patients undergo surgery each year. This study examined which factors were associated with a patient receiving bariatric surgery after referral in a real-world healthcare setting. MATERIALS AND METHODS: The current study used the baseline survey and electronic medical record (EMR) data from the Bariatric Experience Long Term (BELONG) study (n = 1975). Predictors of who did (n = 1680) and who did not (n = 295) have surgery were analyzed using multivariate logistic regression. RESULTS: Participants (n = 1975; 42.4% response rate) were primarily women (84%) and either non-Hispanic Black or Hispanic (60%). In the fully adjusted multivariate model, the strongest predictors of having surgery were being a woman (OR = 3.17; 95% CI = 2.15, 4.68; p < .001) and losing at least 5% of their body weight in the year before surgery (OR = 3.16; 95% CI = 2.28, 4.38; p < .001). The strongest predictors of not having surgery were a ≥ BMI 50 kg/m2 (OR = .39; 95% CI = .27, .56; p < .001) and having a higher physical comorbidity burden (OR = .84; 95% CI = .75, .94; p = .004). CONCLUSIONS: Practices such as 5-10% total weight loss before surgery and selection of patients with safer operative risk profiles (younger with lower comorbidity burden) may inadvertently contribute to under-utilization of bariatric surgery among some demographic subpopulations who could most benefit from this intervention.

Si-Miao-Yong-An (SMYA) Decoction May Protect the Renal Function Through Regulating the Autophagy-Mediated Degradation of Ubiquitinated Protein in an Atherosclerosis Model.

Hyperlipidemia is common, and its renal toxicity has attracted a great deal of attention. Si-miao-yong-an (SMYA) is a famous ancient decoction of traditional Chinese medicine (TCM), which is still widely used in clinical treatment. In this study, we observed and explored its efficacy and mechanism in protecting renal function in an atherosclerosis model. The results showed that the serum, Cr urinal KIM-1, and NGAL were significantly decreased in SMYA group. Although SMYA failed to alleviate the lipid accumulation, decrease p-NFκB, or increase SOD in kidney tissue, the levels of ubiquitinated protein and P62 were decreased in SMYA group. What is more, a higher LC3 II level was observed in the SMYA group. In conclusion, these data indicated that SMYA decoction may protect renal function in hyperlipidemia via regulating the autophagy-mediated degradation of ubiquitinated protein.