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Most medicines are coming with toxic and detrimental side effects. In addition, microbials are resisting the medicine. Therefore, alternative drugs with low toxic and side effects and low microbial resistance are needed. Plants offer good potential candidates due to a broad range of chemicals they contain. These chemicals have been studied, and research is still going on to probe chemical properties of plant chemicals. In China, traditional Chinese medicine is practised, whereby plant extracts are obtained, and then sold in packages for reasons like memory enhancement, cancer treatment, boosting immune system, and so on. Among the herbs cultivated in China is Polygonati rhizoma (PGR). This plant contains various bioflavonoids such as diosgenin, kaempferol, catechin, daidzein, and 3 ′ -methoxydaidzein. In this review, we discussed the pharmacological effects of these chemicals, including luteolin antimicrobial activity in a manner that it circumvents antibiotic resistance; rutin antivenom property; kaempferol as an agent that mitigates neuropathic pain; genistein anticancer property; isorhamnetin’s ability to alleviate chronic obstructive pulmonary diseases (COPD); proanthocyanidins’ ability to deal with diabetic neuropathy and analgesic property of catechin.

Pulmonary arterial hypertension (PAH) is a rare and chronic lung vasculature disease characterised by pulmonary vasculature remodelling, including abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional endothelial cells (ECs). Remodelling of the pulmonary vasculature occurs from maturity to senescence, and it has become apparent that cellular senescence plays a central role in the pathogenesis of various degenerative vascular diseases and pulmonary pathologies. Cellular senescence represents a state of stable proliferative arrest accompanied by the senescence-associated secretory phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment. Evidence shows that in PAH patients, higher levels of cytokines, chemokines and inflammatory mediators can be detected and correlate with clinical outcome. Moreover, senescent cells accrue with age in epithelial, endothelial, fibroblastic and immunological compartments within human lungs, and evidence has shown that ECs and PASMCs in lungs from patients with chronic obstructive pulmonary disease were characterised by a higher number of senescent cells. However, there is little evidence uncovering the molecular pulmonary vasculature senescence in PAH. Herein, we review the cellular senescence in pulmonary vascular remodelling, and emphasise its importance in PAH. We further introduce some signalling pathways which might be involved in vasculature senescence and PAH, with the intent to discuss the possibility of the PAH therapy via targeting cellular senescence and reduce PAH progression and mortality.

Partially decellularized tracheal scaffolds have emerged as a potential solution for long-segment tracheal defects. These grafts have exhibited regenerative capacity and the preservation of native mechanical properties resulting from the elimination of all highly immunogenic cell types while sparing weakly immunogenic cartilage. With partial decellularization, new considerations must be made about the viability of preserved chondrocytes. In this study, we propose a multimodal approach for quantifying chondrocyte viability for airway tissue engineering.Tracheal segments (5 mm) were harvested from C57BL/6 mice, and immediately stored in phosphate-buffered saline at -20°C (PBS-20) or biobanked via cryopreservation. Stored and control (fresh) tracheal grafts were implanted as syngeneic tracheal grafts (STG) for 3 months. STG was scanned with micro-computed tomography (μCT) in vivo. STG subjected to different conditions (fresh, PBS-20, or biobanked) were characterized with live/dead assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and von Kossa staining.Live/dead assay detected higher chondrocyte viability in biobanked conditions compared to PBS-20. TUNEL staining indicated that storage conditions did not alter the proportion of apoptotic cells. Biobanking exhibited a lower calcification area than PBS-20 in 3-month post-implanted grafts. Higher radiographic density (Hounsfield units) measured by μCT correlated with more calcification within the tracheal cartilage.We propose a strategy to assess chondrocyte viability that integrates with vivo imaging and histologic techniques, leveraging their respective strengths and weaknesses. These techniques will support the rational design of partially decellularized tracheal scaffolds.N/A Laryngoscope, 2022.

The mitochondrial genome of Liriodendron tulipifera exhibits many ancestral angiosperm features and a remarkably slow evolutionary rate, while mitochondrial genomes of other magnoliids remain yet to be characterized. We assembled nine new mitochondrial genomes, representing all genera of perianth-bearing Piperales, as well as for a member of the sister clade: three complete or nearly complete mitochondrial genomes from Aristolochiaceae and six additional draft assemblies including Thottea, Asaraceae, Lactoridaceae, and Hydnoraceae. For comparative purpose, a complete mitochondrial genome was assembled for Saururus, a member of the perianth-less Piperales. The average number of short repeats (50–99 bp) was much larger in genus Aristolochia than in other angiosperm mitochondrial genomes, and approximately 30% of repeats ( T:A substitutions of all other investigated angiosperm groups. Our study reports the first mitochondrial genomes for Piperales and uses this new information for a better understanding of the evolutionary patterns of magnoliids and angiosperms in general.

Background Fibroblasts (FBs) have been widely used as a typical in vitro cell model for investigating the biological processes and cell pathophysiological mechanisms. However, FBs are prone to senescence in cell culture process after several passages. Thus, a new approach to cell culture is quite required to enhance the viability of cells. Objective To explore a novel method of primary cell culture based on skin FBs. Methods Dermal tissue blocks were obtained from BALB/c neonatal mice and randomly divided into experimental group and control group. The experimental group received the newly improved culture method, namely, continuous adherence subculture of tissue block (CASTB) method; while the traditional subculture method was applied in the control group. Cells at 1st, 5th and 10th passages were collected and identified by using histological/immunohistochemical and western blot analysis. Cellular viability, proliferation, senescence and apoptosis were analyzed through application of cell growth curve, CCK-8 assay, Ki67 assay, β-galactosidase staining, flow cytometry and western blot analysis. Results Cells under two culture patterns showed vimentin positive expression via immunohistochemistry and western blot assay. With the increase of passage times, the cellular growth rate in the control group gradually decreased, but no alterations emerged from the experimental group. CASTB remarkably promoted cell growth and proliferation. Besides, a lower apoptosis tendency emerged from the experimental group than the control goup with the increasing passages. Conclusion The method of CASTB may offer a large number of primary FBs with higher efficiency and success rate, which is worth of further popularization and application.

Aristolochia, a genus in the magnoliid order Piperales, has been famous for centuries for its highly specialized flowers and wide medicinal applications. Here, we present a new, high-quality genome sequence of Aristolochia fimbriata, a species that, similar to Amborella trichopoda, lacks further whole-genome duplications since the origin of extant angiosperms. As such, the A. fimbriata genome is an excellent reference for inferences of angiosperm genome evolution, enabling detection of two novel whole-genome duplications in Piperales and dating of previously reported whole-genome duplications in other magnoliids. Genomic comparisons between A. fimbriata and other angiosperms facilitated the identification of ancient genomic rearrangements suggesting the placement of magnoliids as sister to monocots, whereas phylogenetic inferences based on sequence data we compiled yielded ambiguous relationships. By identifying associated homologues and investigating their evolutionary histories and expression patterns, we revealed highly conserved floral developmental genes and their distinct downstream regulatory network that may contribute to the complex flower morphology in A. fimbriata. Finally, we elucidated the genetic basis underlying the biosynthesis of terpenoids and aristolochic acids in A. fimbriata.

Aim. This study aimed to learn the antineoplastic activity of curcumol (Cur) on prostate cancer (PCa) and elucidate its potential molecular mechanism. Methods. The proliferation, invasion, and migration of PCa cells (PC3 and 22RV1) were detected by the cell counting kit 8 (CCK8), transwell, and wound healing assay, respectively. The expression of genes and proteins was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB), respectively. The protein expression in tissues and cells was tested through immunohistochemistry (IHC) and immunocytochemistry (ICC). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the level of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The interaction between microRNA125a (miR-125a) and the signal transducer and activator of transcription 3 (STAT3) was confirmed via dual-luciferase reporter assay. Results. Cur effectively restrained the proliferation, invasion, and migration of PC3 and 22RV1 cells. After Cur intervention, miR-125a, miR-375, miR-149, miR-183, and miR-106b were all upregulated in PC3 cells, among which miR-125a was the most significantly upregulated. Dual-luciferase reporter assay combined with qRT-PCR and WB experiments confirmed that miR-125a targeted STAT3. Both in vitro and in vivo, Cur enhanced miR-125a expression and suppressed the activation of the STAT3 pathway in PCa. Also, Cur effectively inhibited the growth of PCa. Conclusion. Cur inhibited the development of PCa by miR-125a/STAT3 axis. This may provide a potential agent for treating PCa.

Brain-on-a-chip is a miniaturized engineering platform to mimic the structural and functional aspects of brain tissue. We describe a method to construct a three-dimensional (3D) brain-on-a-chip in this chapter. We firstly portray the method of a brain-on-a-chip model with cocultured mice neurons, microglia, and astrocytes to mimic brain tissue and membrane-free perfusion with endothelial cells, in which we successfully build the blood-brain barrier to screen neurotoxicity. Then we describe a method to construct a brain-on-a-chip with human induced pluripotent stem cell (iPSC)-derived neurons and astrocytes to simulate human brain behavior. This platform consists of neuronal tissue with extracellular matrix (ECM)-embedded GABAergic neurons and astrocytes and a perfusion channel with dynamic flow. We also include the broader applicability test of this model using an organophosphate (OP), malathion, to induce acute and chronic neurotoxicity, and then using butyrylcholinesterase (BuChE) as an exogenous bioscavenger of OP. Following the methods listed in this chapter, we are able to measure the neurotoxic effects on construct integrity, viability, and total AChE and BuChE activity.

Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches, however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro, however, they do not improve graft epithelialization in vivo.

Despite advances in surgical technique, postoperative hemorrhage remains a common cause of mortality and morbidity for patients following tonsillectomy. Application of biomaterials at the time of tonsillectomy can potentially accelerate mucosal wound healing and eliminate the risk of post-tonsillectomy hemorrhage (PTH). To understand the current state and identify possible routes for the development of the ideal biomaterials to prevent PTH, topical biomaterials for eliminating the risk of PTH were reviewed. Alternative topical biomaterials that hold the potential to reduce the risk of PTH were also summarized.

Inflammation is a defensive response of the body and is at the center of many diseases' process like depression. High mobility group protein box 1 (HMGB1), has been proved to function as a pro-inflammatory cytokine. We aim to explore the role of HMGB1 played in the neuroinflammation here. In this study, we used LPS to induce an acute inflammatory response, and to measure the anti-neuroinflammation effect of icariin (ICA) and icaritin (ICT). We found that LPS could increase the expression of HMGB1 in serum and hippocampus, along with a high expression of HMGB1 in the cytoplasm and a high expression of RAGE, which could be rescued by ICA and ICT, and ethyl pyruvate (EP) pretreatment showed similar effects here. We speculated that the translocation of HMGB1 from the nucleus to the cytoplasm played an important role in neuroinflammatory process, and HMGB1-RAGE signal was involved in this process. Furthermore, we found that ICA and ICT treatment activated TLR4-XBP1s related NF-κB signal, which we thought was relevant with the neuroprotective effect of ICA and ICT. However, EP pretreatment suppressed TLR4-XBP1s- endoplasmic reticulum stress related NF-κB signal to anti-inflammatory response, which was almost absolutely opposite with ICA and ICT treatment. We speculated that it might be caused by the duration of inflammation. We supposed that ICA and ICT could ameliorate neuroinflammation in hippocampus via suppressing HMGB1-RAGE signaling and might show a neuroprotective effect via activating TLR4-XBP1s related NF-κB signal at the same time, making it possible to act as an anti-neuroinflammatory drugs.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world. Inhibitor of differentiation 1 (Id1) is overexpressed in NSCLC and involved in promoting its progression and metastasis. Identifying natural compounds targeting Id1 may have utility in NSCLC treatment. Here, we sought to determine whether the anti-tumor activities of Scutellaria flavonoids (SFs) were related to Id1. We reported that three SFs (baicalin, baicalein and wogonin) exhibited strong antitumor activity in NSCLC cells in vitro and in vivo. Id1 played a pivotal role on blockage of migration and invasion by SFs. Abrogation of invasion and migration mediated by baicalin, baicalein and wogonin were totally abolished by ectopic overexpression of Id1. Mechanistically, baicalin, baicalein and wogonin activated Rap1-GTP binding and dephosphorylated Akt and Src by suppressing a7nAChR, consequently triggering inhibition of Id1. Then attenuation of its downstream mediators, VEGF-A, N-cadherin, vimentin, combined with augment of E-cadherin led to the blockage of proliferation, EMT and angiogenesis of NSCLC. Overall, our data shed light on heretofore-undescribed role of SFs as modulators of Id1, which may be a useful strategy in the treatment of NSCLC.

Objectives/hypothesis Tissue-engineered tracheal grafts (TETGs) offer a potential solution for repair of long-segment airway defects. However, preclinical and clinical TETGs have been associated with chronic inflammation and macrophage infiltration. Macrophages express great phenotypic heterogeneity (generally characterized as classically activated [M1] vs. alternatively activated [M2]) and can influence tracheal repair and regeneration. We quantified and characterized infiltrating host macrophages using mouse microsurgical tracheal replacement models. Study design Translational research, animal model. Methods We assessed macrophage infiltration and phenotype in animals implanted with syngeneic tracheal grafts, synthetic TETGs, or partially decellularized tracheal scaffolds (DTSs). Results Macrophage infiltration was observed following tracheal replacement with syngeneic trachea. Both M1 and M2 macrophages were present in native trachea and increased during early tracheal repair (P = .014), with an M1/M2 ratio of 0.48 ± 0.15. In contrast, orthotopic implantation of synthetic TETGs resulted in a shift to M1 predominant macrophage phenotype with an increased M1/M2 ratio of 1.35 ± 0.41 by 6 weeks following implant (P = .035). Modulation of the synthetic scaffold with the addition of polyglycolic acid (PGA) resulted in a reduction of M1/M2 ratio due to an increase in M2 macrophages (P = .006). Using systemic macrophage depletion, the M1/M2 ratio reverted to native values in synthetic TETG recipients and was associated with an increase in graft epithelialization. Macrophage ratios seen in DTSs were similar to native values. Conclusions M1 and M2 macrophages are present during tracheal repair. Poor epithelialization with synthetic TETG is associated with an elevation of the M1/M2 ratio. Macrophage phenotype can be altered with scaffold composition and host-directed systemic therapies. DTSs exhibit M1/M2 ratios similar to those seen in native trachea and syngeneic tracheal replacement. Level of evidence NA Laryngoscope, 2021.

Decellularized tracheal scaffolds offer a potential solution for the repair of long-segment tracheal defects. However, complete decellularization of trachea is complicated by tracheal collapse. We created a partially decellularized tracheal scaffold (DTS) and characterized regeneration in a mouse model of tracheal transplantation. All cell populations except chondrocytes were eliminated from DTS. DTS maintained graft integrity as well as its predominant extracellular matrix (ECM) proteins. We then assessed the performance of DTS in vivo. Grafts formed a functional epithelium by study endpoint (28 days). While initial chondrocyte viability was low, this was found to improve in vivo. We then used atomic force microscopy to quantify micromechanical properties of DTS, demonstrating that orthotopic implantation and graft regeneration lead to the restoration of native tracheal rigidity. We conclude that DTS preserves the cartilage ECM, supports neo-epithelialization, endothelialization and chondrocyte viability, and can serve as a potential solution for long-segment tracheal defects.

Collagen is the most abundant airway extracellular matrix component and is the primary determinant of mechanical airway properties. Abnormal airway collagen deposition is associated with the pathogenesis and progression of airway disease. Thus, understanding how collagen affects healthy airway tissue mechanics is essential. The impact of abnormal collagen deposition and tissue stiffness has been an area of interest in pulmonary diseases such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In this review, we discuss (1) the role of collagen in airway mechanics, (2) macro- and micro-scale approaches to quantify airway mechanics, and (3) pathologic changes associated with collagen deposition in airway diseases. These studies provide important insights into the role of collagen in airway mechanics. We summarize their achievements and seek to provide biomechanical clues for targeted therapies and regenerative medicine to treat airway pathology and address airway defects.

Aristolochia, a genus in the magnoliid order Piperales, has been famous for centuries for its highly specialized flowers and wide medicinal applications. Here, we present a new, high-quality genome sequence of Aristolochia fimbriata, a species that, similar to Amborella trichopoda, lacks further whole-genome duplications since the origin of extant angiosperms. As such, the A. fimbriata genome is an excellent reference for inferences of angiosperm genome evolution, enabling detection of two novel whole-genome duplications in Piperales and dating of previously reported whole-genome duplications in other magnoliids. Genomic comparisons between A. fimbriata and other angiosperms facilitated the identification of ancient genomic rearrangements suggesting the placement of magnoliids as sister to monocots, whereas phylogenetic inferences based on sequence data we compiled yielded ambiguous relationships. By identifying associated homologues and investigating their evolutionary histories and expression patterns, we revealed highly conserved floral developmental genes and their distinct downstream regulatory network that may contribute to the complex flower morphology in A. fimbriata. Finally, we elucidated the genetic basis underlying the biosynthesis of terpenoids and aristolochic acids in A. fimbriata.

OBJECTIVES/HYPOTHESIS The ideal trachea replacement would be a living graft that is genetically identical to the host, avoiding the need for immunosuppression. We have developed a mouse model of syngeneic tracheal transplant that results in long-term survival without graft stenosis or delayed healing. To understand how host cells contribute to tracheal transplant integration, we quantified the populations of host cells in the graft and native trachea following implant. STUDY DESIGN Tracheal transplant, tracheal replacement, regenerative medicine, animal model. METHODS Tracheal grafts were obtained from female C57BL/6 mice and orthotopically transplanted into syngeneic male recipients. Cohorts were euthanized on day 14, day 45, and day 90 post-transplantation. Host and graft tracheas were explanted and analyzed by histology. Male host cells were quantified using fluorescence in situ hybridization, and macrophages were quantified with immunofluorescence. RESULTS Evidence of host-derived cells was found in the midgraft at the earliest time point (14 days). Host-derived cells transiently increased in the graft on day 45 and were predominantly found in the submucosa. By day 90, the population of host-derived cells population declined to a similar level on day 14. Macrophage infiltration of host and graft tissue was observed at all time points and was greatest on day 90. CONCLUSIONS Tracheal graft integration occurs by way of subacute transient host-cell infiltration and is primarily inflammatory in nature. Host-cell contribution to the graft epithelium is limited. These data indicate that creation of living, nonimmunogenic tracheal graft could serve as a viable solution for long-segment tracheal defects. LEVEL OF EVIDENCE 3 Laryngoscope, 131:E340-E345, 2021.

To verify the Traditional Chinese Medicine (TCM) theory that kidney-Qi deficiency (KQD) is considered to be the main cause of aging using cross-sectional study.Demographic and lifestyle characteristics of 90 healthy participants were collected with a self-administered questionnaire. KQD syndrome was diagnosed according to Deng's diagnosis standard. Creatinine-adjusted urinary 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and 8-isomeric-prostaglandin2α (8-iso-PGF2α), salivary advanced oxidation protein products (AOPPs), malondialdehyde (MDA) and dehydroepiandrosterone-sulfate (DHEA-S) were selected as aging markers and measured using enzyme-linked immunosorbent assay.No significant differences were observed in participant characteristics between the KQD group and non-KQD (NKQD) group (P0.05). Levels of 8-OH-dG, 8-iso-PGF2α, AOPPs, and MDA increased with age, except for a slight decrease in 8-OH-dG in the older group. The increase in 8-iso-PGF2α was significant (P0.05). DHEA-S significantly decreased with increasing age (P0.01). 8-OH-dG levels were higher in the KQD group compared with the NKQD group. Levels of urinary 8-iso-PGF2α, salivary AOPPs, and MDA in the KQD group were lower than in the NKQD group. Salivary DHEA-S was higher in the KQD group compared with the NKQD group. However, differences between KQD group and NKQD group were not significant.The current results suggested that KQD syndrome, as diagnosed by Deng's standard, does not underlie the aging phenotype.

Diabetes mellitus increases the risk of dementia, and evidence suggests hyperglycemia is a key contributor to neurodegeneration. However, our understanding of diabetes-associated cognitive decline, an important complication of diabetes mellitus, is lacking and the underlying mechanism is unclear. Blood brain barrier (BBB) breakdown is a possible cause of dementia in diabetes mellitus and Alzheimer's disease. Accumulating evidence shows BBB dysfunction caused by hyperglycemia contributes to cognitive decline. A specific type of inflammatory programmed cell death, called pyroptosis, has potential as a therapeutic target for BBB-associated diseases. Potential inducers of pyroptosis include inflammasomes such as NLRP3, whose activation relies on damage-associated molecular patterns. High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein found in most cell types, and acts as a damage-associated molecular pattern when released from the nucleus. We propose that HMGB1 influences vascular inflammation by activating the NLRP3 inflammasome and thereby initiating pyroptosis in vascular cells. Moreover, HMGB1 plays a pivotal role in the pathogenesis of diabetes mellitus and diabetic complications. Here, we review the role of HMGB1 in BBB dysfunction induced by hyperglycemia and propose that HMGB1 is a promising therapeutic target for countering diabetes-associated cognitive decline.

Objective: The objective of this study is to preliminarily evaluate the efficacy of the combination of baicalein and docetaxel on non-small cell lung cancer (NSCLC) in vivo. Methods: The subcutaneous model was established by inoculation of A549 cells, and then these tumor-bearing mice were randomly assigned to eight groups to receive normal saline (NS) as control, baicalein alone, Taxotere[Formula: see text] (docetaxel injection) alone or the combination of baicalein and Taxotere[Formula: see text]. The effect of the combination treatment was evaluated by [Formula: see text] value. Tumors were harvested for TUNEL and CD31 immunohistochemical staining and important organs for H&E staining. Results: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg significantly reduced tumor weight and inhibited the growth rate of tumor, displaying the additive effect indicated by the [Formula: see text] value. Increased apoptosis and decreased tumor angiogenesis also provided pathological evidence. Additionally, baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg did not increase toxicity in lung, liver and kidney. Conclusion: Baicalein 50[Formula: see text]mg/kg plus docetaxel 10[Formula: see text]mg/kg additively inhibits the growth of NSCLC in vivo, and the mechanism underlying remains to be discovered.

High mobility group protein box 1 (HMGB1), a sophisticated danger signal with pleiotropic functions, has been proved to function as a pro-inflammatory cytokine. In the central neural system (CNS), HMGB1 can stimulate microglia, the immune cell in the CNS, to release inflammatory factors and to cause chronic neurodegeneration. The evidence showed that HMGB1 can act as a pro-inflammatory cytokine mainly through its receptors like advanced glycation end product (RAGE), Toll-like 4 (TLR4), and so on. Moreover, HMGB1 contributed to the priming effects of stress-pretreatment and played a key role in neurodegeneration diseases via mediating neuroinflammation. However, the evidence also showed that HMGB1 played a role in tissue repair, with the ability to promote cell migration and proliferation, to induce the differentiation of mesenchymal stem cells (MSCs), and to regenerate spinal cord. These pleiotropic functions of HMGB1 make it possible to play a role from cell death to new life. Depression is a chronic, severe, and often life-threatening disease accompanied with impaired neurogenesis. The evidence showed that neuroinflammation played a key role in the process of depression. Depressive patients often showed a high expression of inflammatory cytokines in the blood and an activation of microglia in the brain. Meanwhile, they also showed a neuron deficit in the brain. Though they lack direct evidence linking HMGB1 with depression, the ability of HMGB1 that can function from neuroinflammation to tissue repair makes HMGB1 a promising therapeutic target of depression.

Objective: The aim of this study is finding an optimal and convenient aging marker. Method: The information of participants’ occupation, family background, life style, physical condition, etc. was obtained by a self-administered questionnaire. Spot urine and saliva samples were collected during the early morning after fasting overnight. 8-hydroxydeoxygunaosine (8-OHdG), 8-iso-prostaglandin F2[Formula: see text] (8-isoPGF2[Formula: see text]), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and dehydroepian drosterone sulfate (DHEA-S) were measured by ELISA. Results: Around 112 non-smokers (males/females [Formula: see text] 61/51; mean age [Formula: see text] 44.9 years) were eligible and analyzed in this study. The mean urinary 8-OHdG level was [Formula: see text] (ng/mmol, creatinine) and mean 8-isoPGF2[Formula: see text] level was [Formula: see text] (pg/mmoL, creatinine). In saliva, the mean level of AOPPs, MDA, and DHEA-S was [Formula: see text] ([Formula: see text]mol/L), [Formula: see text] ([Formula: see text]mol/L) and [Formula: see text] (ng/mL), respectively. After analysis in multiple regression model, urinary 8-OHdG was influenced by age and tea consumption ([Formula: see text]); urinary 8-isoPGF2[Formula: see text] level was correlated with gender ([Formula: see text]); salivary DHEA-S was related to gender ([Formula: see text]) and marital status ([Formula: see text]); AOPPs and MDA in saliva presented no relationships with those factors. Conclusion: Among healthy non-smokers, urinary 8-OHdG is the best aging biomarker comparing to other markers.

Icariin is a main component of the Chinese medicinal plant Epimedium brevicornu Maxim, exhibits potent activity against inflammatory diseases. Our previous data demonstrated the valid bioactivity of icariin on mitigating rodent asthma. Endoplasmic reticulum (ER) stress and nuclear factor-κB (NF-κB) pathway were involved in the pathogenesis of asthma. However, it remains poorly defined that whether icariin could inhibit ER stress and NF-κB mediated apoptosis in asthma and further influence the central neural system. Herein, we investigated the effects of icariin on primary cultured fetal rat hippocampal neurons and OVALPS-OVA induced asthma rat model. Asthma rat models were established by ovalbumin (OVA) and lipopolysaccharide (LPS) intraperitoneal injection and OVA inhalational challenge. Airway resistance was analyzed to evaluate lung function after last challenge and pathological changes were detected on lung tissues. Assessment of inflammatory cells counts in bronchoalveolar lavage fluids (BALF) were performed and ELISA was used to determine levels of interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ in serum. Protein expression of BiP and IRE-1α, XBP-1s and phosphorylation-IκBα (p-IκBα), IκBα, and p65 as well as cytochrome c, caspase-3 (cleaved caspase-3), and caspase-9 (cleaved caspase-9) were tested by Western blot. We found that icariin could remarkably improve pulmonary function and reduce inflammatory cells in the lung, levels of inflammatory cytokines, and ER stress related proteins as well as NF-κB were prominently suppressed by icariin. Our results suggested that icariin had an inhibitory effect on airway inflammation and neuroprotective effect on ER stress and NF-κB mediated apoptosis in asthma rats and cultured fetal rat hippocampal neurons, which may provide new mechanistic insights into the asthma prevention and treatment of icariin.