Search

Xiao-yu Liang,1 Fen-Fang Hong,2 Shu-Long Yang1 1Department of Physiology, College of Medicine, Nanchang University, Nanchang, 330006, People’s Republic of China; 2Experimental Teaching Center, Nanchang University, Nanchang, 330031, People’s Republic of ChinaCorrespondence: Shu-Long YangDepartment of Physiology, College of Medicine, Nanchang University, Nanchang, 330006, People’s Republic of ChinaTel +86 13576291532Email slyang@ncu.edu.cnFen-Fang HongExperimental Teaching Center, Nanchang University, Nanchang, 330031, People’s Republic of ChinaTel +86 18970965319Email hongfenfang@126.comPurpose: Non-alcoholic fatty liver disease (NAFLD) is the main form of chronic liver disease in the world. Astragaloside IV (ASIV) has been tested in experimental models of different diseases. The purpose of this study was to evaluate the effect and protective mechanism of ASIV on NAFLD.Methods: Lipopolysaccharide (LPS)- and palmitate acid (PA)-induced RAW264.7 cells and LO2 cells were used as a NAFLD model. The mice NAFLD model was evaluated by hematoxylin-eosin staining (HE staining), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Liver lipid metabolism was evaluated by triglyceride (TG) and total cholesterol (TC) kits and oil red O staining. Oxidative stress indicators were examined through biochemical methods. Inflammatory factors were explored through enzyme-linked immuno sorbent assay (ELISA), real-time quantitative PCR and oxidative stress indicator kits. The expression levels of 5-LO (5-lipoxygenase) and leukotriene A4 hydrolase (LTA4H) were checked by real-time quantitative PCR and Western blotting. Apoptosis was detected by Annexin V-FITC/PI cell apoptosis detection kit.Results: Our results showed that in vivo ASIV significantly reduced liver tissue damage, and serum AST, ALT and serum TG levels in NAFLD mice. In vitro, ASIV reduced cell supernatant TG and TC content increased by PA treatment, and significantly decreased the accumulation of intracellular lipid droplets induced by PA treatment. Additionally, ASIV reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and restored glutathione peroxidase (GSH-Px) levels in PA-treated LO2 cell supernatant. Furthermore, ASIV inhibited the production of proinflammatory cytokines (IL-6 and TNF-α) in RAW264.7 cells induced by LPS. We also found that ASIV downregulated the expression of 5-LO and LTB4 (leukotriene B4) in NAFLD mice. Moreover, ASIV restored apoptotic protein (Bax and Bcl-2) expression in PA-treated LO2 cells.Conclusion: ASIV may reduce liver steatosis, hepatocyte oxidative stress and apoptosis, and decrease liver inflammation, thereby attenuating the progression of NAFLD and thus might be of therapeutic interest.Keywords: astragaloside IV, non-alcoholic fatty liver disease, lipid accumulation, oxidative stress, apoptosis

The treatment of internal hemorrhage remains challenging due to the current limited antibacterial capability, hemostatic efficacy, and biocompatibility of hemostatic materials. The TEMPO-oxidized cellulose nanofibers/collagen/chitosan (TCNF/COL/CS) hemostatic aerogel was developed in this work by physically encasing COL in a sandwich structure and electrostatically self-assembling polyanionic TCNF with polycationic CS. In vitro coagulation experiments revealed the favorable procoagulant properties of TCNF/COL/CS along with high adhesion to erythrocytes and platelets. TCNF/COL/CS significantly increased the hemostatic efficacy by 59.8 % and decreased blood loss by 62.2 % in the liver injury model when compared to Surgicel®, the most frequently used hemostatic material. Furthermore, it demonstrated outstanding biodegradability both in vitro and in vivo , and a substantial increase in resistance (96.8 % against E. coli and 95.4 % against S. aureus ) compared to TCNF. The significant hemostatic and biodegradable characteristics of TCNF/COL/CS can be ascribed to its interconnected porous structure, increased porosity, and efficient water absorption, along with the synergistic effect of the three constituents. The TCNF/COL/CS aerogel shows significant potential to control internal bleeding. A novel plant-derived nanocellulose composite aerogel has been described here for the first time; it has outstanding antibacterial characteristics, higher biocompatibility, and outstanding hemostatic characteristics in vivo ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The surface properties of cardiovascular biomaterials play a critical role in their biological responses. Although bacterial nanocellulose (BNC) materials have exhibited potential applications in cardiovascular implants, the impact of their surface characteristics on biocompatibility has rarely been studied. This study investigated the mechanism for the biocompatibility induced by the physicochemical properties of both sides of BNC. With greater wettability and smoothness, the upper BNC surface reduced protein adsorption by 25 % compared with the lower surface. This prolonged the plasma re-calcification time by 14 % in venous blood. Further, compared with the lower BNC surface, the upper BNC surface prolonged the activated partial thromboplastin time by 5 % and 4 % in arterial and venous blood, respectively. Moreover, the lower BNC surface with lesser rigidity, higher roughness, and sparser fiber structure promoted cell adhesion. The lower BNC surface enhanced the proliferation rate of L929 and HUVECs cells by 15 % and 13 %, respectively, compared with the upper BNC surface. With lesser stiffness, the lower BNC surface upregulated the expressions of CD31 and eNOS while down-regulating the ICAM-1 expression - This promoted the proliferation of HUVECs. The findings of this study will provide valuable insights into the design of blood contact materials and cardiovascular implants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

There is an increasing demand for small-diameter blood vessels. Currently, there is no clinically available small-diameter artificial vessel. Bacterial nanocellulose (BNC) has vast potential for applications in artificial blood vessels due to its good biocompatibility. At the same time, medical polyurethane (PU) is a highly elastic polymer material widely used in artificial blood vessels. This study reports a composite small-diameter BNC/PU conduit using a non-solvent-induced phase separation method with the highly hydrophilic BNC tube as the skeleton and the hydrophobic polycarbonate PU as the filling material. The results revealed that the compliance and mechanical matching of BNC/PU tubes were higher than BNC tubes; the axial/radial mechanical strength, burst pressure, and suture strength were significantly improved; the blood compatibility and cell compatibility were also excellent. The molecular and subcutaneous embedding tests showed that the composite tubes had lighter inflammatory reactions. The results of the animal substitution experiments showed that the BNC/PU tubes kept blood flow unobstructed without tissue proliferation after implantation in rats for 9 months. Thus, the BNC/PU small-diameter vascular prosthesis had the potential for long-term patency and acted as an ideal material for small-diameter vessels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of bio-based hemodialysis membranes continues to be a challenge. Bacterial nanocellulose (BNC) membranes show potential in hemodialysis but can hardly retain beneficial proteins. Here, chitosan particles/bacterial nanocellulose (CSP/BNC) membranes were designed to efficiently remove uremic toxins and retain beneficial proteins. First, CSPs were synthesized in situ within a BNC membrane by ionic gelation following negative pressure impregnation. Subsequently, these membranes were thoroughly characterized. Compared with the BNC membrane, the pore volume and pore size of the 3 % CSP/BNC membrane decreased by 42.2 % and 32.1 %, respectively. The increased 22.2 times of Young's modulus and 88.9 % of tensile strength in the 3 % CSP/BNC membrane confirmed enhanced mechanical property. The sieving coefficient of bovine serum albumin decreased to 0.05 ± 0.03 in the 3 % CSP/BNC membrane. Moreover, the CSP/BNC membrane exhibited good hemocompatibility and cytocompatibility. The simulated dialysis results showed that the 3 % CSP/BNC membrane exhibited high clearance of urea (16.37 %/cm 2 ) and lysozyme (3.54 %/cm 2 ), while efficiently retaining bovine serum albumin (98.04 %/cm 2 ). This is the first demonstration of the construction of a BNC-based hemodialysis membrane with in situ CSP formation to effectively regulate the pore properties of the membrane, making the CSP/BNC membrane a promising candidate for hemodialysis applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies have shown that non-alcoholic fatty liver disease (NAFLD) may be associated with sleep disorders. In order to explore the explicit relationship between the two, we systematically reviewed the effects of sleep disorders, especially obstructive sleep apnea (OSA), on the incidence of NAFLD, and analyzed the possible mechanisms after adjusting for confounding factors. NAFLD is independently associated with sleep disorders. Different sleep disorders may be the cause of the onset and aggravation of NAFLD. An excessive or insufficient sleep duration, poor sleep quality, insomnia, sleep-wake disorders, and OSA may increase the incidence of NAFLD. Despite that some research suggests a unidirectional causal link between the two, specifically, the onset of NAFLD is identified as a result of changes in sleep characteristics, and the reverse relationship does not hold true. Nevertheless, there is still a lack of specific research elucidating the reasons behind the higher risk of developing sleep disorders in individuals with NAFLD. Further research is needed to establish a clear relationship between NAFLD and sleep disorders. This will lay the groundwork for earlier identification of potential patients, which is crucial for earlier monitoring, diagnosis, effective prevention, and treatment of NAFLD., Competing Interests: Conflict-of-interest statement: All authors have no relevant conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The development of bacterial cellulose (BC) industrialization has been seriously affected by its production. Mannose/mannan is an essential component in many biomass resources, but Komagataeibacter xylinus uses mannose in an ineffective way, resulting in waste. The aim of this study was to construct recombinant bacteria to use mannose-rich biomass efficiently as an alternative and inexpensive carbon source in place of the more commonly used glucose. This strategy aimed at modification of the mannose catabolic pathway via genetic engineering of K. xylinus ATCC 23770 strain through expression of mannose kinase and phosphomannose isomerase genes from the Escherichia coli K-12 strain. Recombinant and wild-type strains were cultured under conditions of glucose and mannose respectively as sole carbon sources. The fermentation process and physicochemical properties of BC were investigated in detail in the strains cultured in mannose media. The comparison showed that with mannose as the sole carbon source, the BC yield from the recombinant strain increased by 84%, and its tensile strength and elongation were increased 1.7 fold, while Young's modulus was increased 1.3 fold. The results demonstrated a successful improvement in BC yield and properties on mannose-based medium compared with the wild-type strain. Thus, the strategy of modifying the mannose catabolic pathway of K. xylinus is feasible and has significant potential in reducing the production costs for industrial production of BC from mannose-rich biomass., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Size and properties of tubular bacterial nanocellulose (BNC) can be regulated by controllable mercerization with thinner tube walls, better mechanical properties, and improved biocompatibility. Although mercerized BNC (MBNC) conduits have considerable potential as small-caliber vascular grafts (<6 mm), poor suture retention and lack of compliance that cannot match natural blood vessels increase the difficulty of surgery and limit potential clinical application. Polyvinyl alcohol (PVA) is a kind of hydrophilic polymer with good biocompatibility and elasticity, which can precipitate in alkaline solutions. In this study, novel elastic mercerized BNC/PVA conduits (MBP) are manufactured combining mercerization of BNC tubes with precipitation and phase separation of PVA with thinner tube wall, improved suture retention, better elasticity, good hemocompatibility and great cytocompatibility. The MBP obtained with 12.5 % PVA is selected for transplantation in a rat abdominal aorta model. For 32 weeks, normal blood flow is observed using Doppler sonographic inspection, which demonstrates long-term patency. Immunofluorescence staining results also indicate the formation of endothelium and smooth muscle layers. The results indicate the introduction of PVA, and its phase separation into mercerization of tubular BNC can endow MBP conduits with better compliance and suture retention, making it a promising candidate for blood vessel replacement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe joint damage and disability. However, the specific mechanism of RA has not been thoroughly clarified over the past decade. Nitric oxide (NO), a kind of gas messenger molecule with many molecular targets, is demonstrated to have significant roles in histopathology and homeostasis. Three nitric oxide synthases (NOS) are related to producing NO and regulating the generation of NO. Based on the latest studies, NOS/NO signaling pathways play a key role in the pathogenesis of RA. Overproduction of NO can induce the generation and release of inflammatory cytokines and act as free radical gas to accumulate and trigger oxidative stress, which can involve in the pathogenesis of RA. Therefore, targeting NOS and its upstream and downstream signaling pathways may be an effective approach to managing RA. This review clearly summarizes the NOS/NO signaling pathway, the pathological changes of RA, the involvement of NOS/NO in RA pathogenesis and the conventional and novel drugs based on NOS/NO signaling pathways that are still in clinical trials and have good therapeutic potential in recent years, with an aim to provide a theoretical basis for further exploration of the role of NOS/NO in the pathogenesis, prevention and treatment of RA.

Therapeutic benefits of small caliber artificial blood vessels to cure cardio and cerebrovascular diseases are mainly limited by their low patency during long-term transplantation. Bacterial nanocellulose (BNC), as a natural polysaccharide mainly synthesized by a bacterium Komagataeibatacter xylinus, has shown great potential in small-caliber vascular graft applications due to its shape controllability, and furthermore its physical surface structure can be adjusted with different treatments. However, influences of physical surface structure and properties of BNC conduits on behaviors of vascular cells have not been investigated. In this work, mercerized BNC conduits (MBNC) with different surface roughness and stiffness were constructed by controlled alkali (NaOH) treatment. The changes of surface structures and properties significantly affected the behaviors of vascular cells and gene expression; meanwhile, the cell seeding density also affected the cell responses. After mercerization with NaOH concentration > 10 %, it was observed that the increased stiffness of MBNC decreased several functional gene expressions of human vascular endothelial cells, and the pathological transformation of smooth muscle cells was inhibited. This study demonstrates physical surface structure of MBNC conduits will critically regulate functions and behaviors of vascular cells and it also provides important designing parameters to improve the long-term patency of BNC-based conduits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The treatment for corneal damage requires donor corneal transplantation, but there is a serious scarcity of donor corneas worldwide. In this study, we aimed to design a new artificial cornea with good cytocompatibility, excellent optical properties and suture resistance, and great moisturizing properties. A new bacterial nanocellulose (BNC) membrane with anisotropic mechanical properties and high light transmission was produced in a horizontal rotary drum reactor. However, as a potential material for artificial keratoplasty, the transparency and mechanical properties of the new BNC membrane were not satisfactory. Thus, hyaluronic acid (HA) was introduced in the BNC to synthesize the BNC/HA composite membrane by using 1,4-butanediol diglycidyl ether (BDDE) as the chemical cross-linking agent. The micro-morphology, light transmittance, mechanical properties, water content, moisture retention ability, and cytocompatibility of the composite membranes were further evaluated. HA was fixed in the BNC network by the ether bond, and the composite membrane was found to have excellent light transmittance (up to 95.96%). The composite membrane showed excellent mechanical properties, for instance, its tensile strength exceeded the human normal intraocular pressure (IOP) (1.33-2.80 kPa), the maximum burst pressure was about 130 kPa, 46-97 times that of the normal IOP, and its suture force was close to that of the human amniotic membrane (0.1 N). Based on the three-dimensional network scaffold of BNC and the high water absorption characteristics of HA, the artificial cornea had high water content and high moisture retention ability. The rabbit corneal stromal cells cultured in vitro showed that the artificial cornea substitute had excellent cytocompatibility. BDDE is the most frequently used cross-linker in most HA products in the current cosmetic medicine industry owing to its long-term safety records for over 15 years. Therefore, the BNC/HA composite hydrogel cross-linked with BDDE has great potential in artificial keratoplasty or ocular surface repair.

Low-temperature two-step concentrated H 2 SO 4 was discovered to be a solvent with high cellulose solubility [>300 g/L (17 wt%)], fast cellulose dissolution, high regeneration yield (>0.92 g/g), and cellulose being mouldable during regeneration. The superior performance was enabled by the much better compatibility of cellulose with lower concentrated H 2 SO 4 at low temperature, compared with that of high concentrated H 2 SO 4 . The regenerated cellulose was characterized by mostly unchanged composition and highly tunable degree of polymerization (DP). The H 2 SO 4 starting content, cotton fibre temperature, dissolution temperature, regeneration temperature, regeneration bath and storage time were factors determining the DP of regenerated cellulose, which could be equivalent to 4-90 % of the original cotton. These advantages of the solvent enabled versatile application in fabrication of extra strong cellulose hydrogels, manufacture of strong cellulose fibres, preparation of various homogenous composites which would be prepared with much more difficulty by using other solvents, and facile manufacture of cellooligosaccharides., Competing Interests: Declaration of competing interest There is no financial and personal relationship with other people or organizations that could inappropriately influence the current work., (Copyright © 2022. Published by Elsevier Ltd.)

Autophagy, a vital mechanism restricted in tissues, exerts its cytoprotective role through the degradation mechanism of damaged or aging organelles, harmful protein aggregates and intracellular pathogens, followed by energy furnishment. However, dysfunctional autophagy is associated with the development of autoimmune diseases such as rheumatoid arthritis (RA). In pathological conditions, autophagy may be involved in the maturation, survival and proliferation of various immune and non-immune cells and plays a key role in the pathogenesis of RA. Furthermore, autophagy appears to be involved in the citrullination of T lymphocytes and the presentation of citrullinated peptides, which are presented to T lymphocytes via the major histocompatibility complex, causing immune responses and chronic inflammation, as well as bone and cartilage destruction associated with apoptosis resistance of RA fibroblast-like synoviocyte (RAFLS) and osteoclastogenesis. In this review, we have summarised the roles of autophagy in the pathogenesis of RA including citrullination, immune tolerance break, osteoclastogenesis, RA FLS cell dysplasia, apoptosis resistance, together with the therapeutic potentials of autophagy regulators.

Bacterial nanocellulose (BNC) has received great attention for application as an artificial blood vessel material. However, many results showed that pristine BNC could not perfectly meet all the demands of blood vessels, especially for rapid endothelialization. In order to improve the properties of small-caliber vessels, different concentrations of fish gelatin (Gel) were deposited into the 3D network tubes and their properties were explored. The BNC/Gel composite tubes were treated with glutaraldehyde to crosslink BNC and fish gelatin. Compared with pristine BNC tubes, the BNC/Gel tubes had a certain improvement in mechanical properties. In vitro cell culture demonstrated that the human endothelial cells (HUVECs) and human smooth muscle cells (HSMCs) planted on the internal walls of BNC/Gel tubes showed better adhesion, higher proliferation and differentiation potential, and a better anticoagulation property, as compared to the cells cultured on pristine BNC tubes. Whole-blood coagulation experiments showed that the BNC/Gel tube had better properties than the BNC tube, and the hemolysis rate of all samples was less than 1.0%, satisfying the international standards for medical materials. An increase in the content of fish gelatin also increased the mechanical properties and the biocompatibility of small-caliber vessels. Considering the properties of BNC/Gel tubes, 1.0 wt/v% was selected as the most appropriate concentration of fish gelatin for a composite.

Background: The aim of this study was to shed light on the active ingredients and potential targets of Cassia Seed about anti-atherosclerosis based on network pharmacology., Methods: The active ingredients and potential targets of Cassia Seed were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. Then, atherosclerosis-related targets were screened via GeneCards, online mendelian inheritance in man, therapeutic target database and DrugBank database. The common targets and protein-protein interaction (PPI) network was later identified and built. Furthermore, we used the database for annotation, visualization and integrated discovery (DAVID) database server to accomplish the enrichment analysis. The compounds-targets-pathways network was ultimately constructed by Cytoscape., Results: A total of 14 active ingredients and 475 related targets were sifted from Cassia Seed. Among 574 potential atherosclerotic targets, there were 99 targets overlapped with those of Cassia Seed. Topological analysis with Cytoscape revealed that proto-oncogene tyrosine-protein kinase proto-oncogene tyrosine-protein kinase Src, transcription factor AP-1 (JUN), mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14) and catenin beta-1 were considered as the hub gene. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the Cassia Seed had the potential to influence varieties of biological processes and pathways, including positive regulation of smooth muscle cell proliferation, inflammatory response, tumor necrosis factor (TNF) signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and arachidonic acid (ARA) metabolism., Conclusion: Taken together, our findings support that anti-atherosclerosis effects of Cassia Seed are characterized by multi-component, multi-target and multi-path mechanism of action., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Oxidized bacterial nanocellulose (O-BNC) is a favorable material to subdue bacterial infection because of the carboxylate content that not only has a weak antibacterial activity but also is capable of bonding electrostatically to polycationic antibacterial agents. In this study, the 2,2,6,6-Tetramethylpiperidinyloxy radical (TEMPO)-mediated oxidation of BNC was optimized to achieve high carboxylate content while retaining an acceptable tensile profile. To develop an O-BNC-based functional wound dressing, ε-poly-l-lysine (PLL) was then covalently bonded with O-BNC via 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) reaction after homogeneous distribution by ultrasonication. The antibacterial activity of the obtained wound dressing was significantly higher (p < 0.05), and no toxicity was observed. The infected full-thickness wounds of rats were healed faster (p < 0.05) covered by the dressing due to less inflammation, faster blood vessel proliferation, and epidermal layer formation. The material is an effective and promising functional dressing for the treatment of infected wounds., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Bacterial nanocellulose (BNC) is an excellent candidate biomaterial for wound dressing applications, although its preparation should consider the differences in wound healing resulting from BNC biosynthesized by different bacterial strains. This study design aimed to characterize the BNC produced by three different bacterial strains and compare their effectiveness for wound healing applications. The results demonstrated that the upper surfaces of the BNC membranes were clearly denser and more compact than the lower surfaces, while all varieties were capable of serving as a physical barrier to the invasion of bacteria. The growth of fibroblasts demonstrated that the lower surfaces of BNC membranes exhibited biocompatibility superior to that of the upper surfaces. In vivo analysis indicated that, of all samples, wounds treated with the BNC membrane synthesized by DHU-WX-1 displayed the greatest wound repair efficacy. The results indicate that BNC biosynthesized by different strains displayed different wound healing effectiveness. Placing the lower surface of BNC membranes in contact with wounds, with the denser upper surface outward, satisfied the clinical requirements of a wound repair biomaterial., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is widely known for its multiple systems damage, especially neurocognitive deficits in children. Since their discovery, adenosine A 2A receptors (A 2A Rs) have been considered as key elements in signaling pathways mediating neurodegenerative diseases such as Huntington's and Alzheimer's, as well as cognitive function regulation. Herein, we investigated A 2A R role in cognitive impairment induced by chronic intermittent hypoxia (CIH). Mice were exposed to CIH 7 h every day for 4 weeks, and intraperitoneally injected with A 2A R agonist CGS21680 or A 2A R antagonist SCH58261 half an hour before IH exposure daily. The 8-arm radial arm maze was utilized to assess spatial memory after CIH exposures.To validate findings using pharmacology, the impact of intermittent hypoxia was investigated in A 2A R knockout mice. CIH-induced memory dysfunction was manifested by increased error rates in the radial arm maze test. The behavioral changes were associated with hippocampal pathology, neuronal apoptosis, and synaptic plasticity impairment. The stimulation of adenosine A 2A R exacerbated memory impairment with more serious neuropathological damage, attenuated long-term potentiation (LTP), syntaxin down-regulation, and increased BDNF protein. Moreover, apoptosis-promoting protein cleaved caspase-3 was upregulated while anti-apoptotic protein Bcl-2 was downregulated. Consistent with these findings, A 2A R inhibition with SCH58261 and A 2A R deletion exhibited the opposite result. Overall, these findings suggest that A 2A R plays a critical role in CIH-induced impairment of learning and memory by accelerating hippocampal neuronal apoptosis and reducing synaptic plasticity. Blockade of adenosine A 2A receptor alleviates cognitive dysfunction after chronic exposure to intermittent hypoxia in mice., (Copyright © 2021. Published by Elsevier Inc.)

Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the authors or other coauthors in this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer's disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

Background: Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner., Results: In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacter xylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m 2 /g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin., Conclusion: This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial., (© 2022. The Author(s).)

Autograft is currently the gold standard in the clinical treatment of peripheral nerve injury (PNI), which, however, is limited by the availability of a donor nerve and secondary injuries. Nerve guidance conduits (NGC) provide a suitable microenvironment to promote the regeneration of injured nerves, which could be the substitutes for autografts. In this study, nerve growth factor (NGF) encapsulated chitosan nanoparticles (CSNPs) were first constructed in situ in an oxidized bacterial cellulose (OBC) conduit using the ion gel method after the introduction of a CS/NGF solution under pressure to enable a sustainable release of NGF. A novel NGF@CSNPs/OBC nanocomposite with antibacterial activity, biodegradability, and porous microstructure was successfully developed. In vitro experiments showed that the nanocomposite promoted the adhesion and proliferation of Schwann cells. When the nanocomposite was applied as NGC to repair the sciatic nerve defect of rats, a successful repair of the 10 mm nerve defect was observed after 4 weeks. At week 9, the diameter, morphology, histology, and functional recovery of the regenerated nerve was comparable to the autografts, indicating that the NGC effectively promoted the regeneration and function recovery of the nerve. In summary, the NGF@CSNPs/OBC as a novel NGC provides great potential in the treatment of PNI.

Sleep disorders are common in patients with Alzheimer's disease, and can even occur in patients with amnestic mild cognitive impairment, which appears before Alzheimer's disease. Sleep disorders further impair cognitive function and accelerate the accumulation of amyloid-β and tau in patients with Alzheimer's disease. At present, sleep disorders are considered as a risk factor for, and may be a predictor of, Alzheimer's disease development. Given that sleep disorders are encountered in other types of dementia and psychiatric conditions, sleep-related biomarkers to predict Alzheimer's disease need to have high specificity and sensitivity. Here, we summarize the major Alzheimer's disease-specific sleep changes, including abnormal non-rapid eye movement sleep, sleep fragmentation, and sleep-disordered breathing, and describe their ability to predict the onset of Alzheimer's disease at its earliest stages. Understanding the mechanisms underlying these sleep changes is also crucial if we are to clarify the role of sleep in Alzheimer's disease. This paper therefore explores some potential mechanisms that may contribute to sleep disorders, including dysregulation of the orexinergic, glutamatergic, and γ-aminobutyric acid systems and the circadian rhythm, together with amyloid-β accumulation. This review could provide a theoretical basis for the development of drugs to treat Alzheimer's disease based on sleep disorders in future work., Competing Interests: None

High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A- g -BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A- g -BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A- g -BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.

Vascular dementia (VD), a cerebrovascular disease which causes cognitive impairment, is one of the significant factors that affects the quality of senectitude. Atherosclerosis (AS) is a chronic inflammatory syndrome and closely associated with VD. Analyzing the role of AS in VD contribute greatly to its early detection and prevention, but their relationship has not been integrated into a complete network. This review summarizes AS biomarkers as VD predictors for the first time and describes the direct mechanisms of AS causing VD from five aspects: vascular morphogenesis, hemodynamic change, neurovascular unit damage (NVU), oxidative stress, and microRNA (miRNA). Finally, it discriminates the relationship between AS and VD in common risk factors which can be disease or some molecules. In particular, these data imply that the role of AS in VD is not only a pathogenic factor but also a comorbidity in VD. This review aims to bring new ideas for the prediction and treatment of VD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Hong and Yang.)

Incorporation of chitosan (CS) into Bacterial nanocellulose (BNC) matrix is of great interests in biomedical field due to the advantageous properties of each material. However, the conventional strategies result in poor composite effect with low efficiency. In this study, the three-dimensional fibrillar network of BNC was utilized as a template for the first time to homogeneously disperse CS to form nanoparticles (CSNPs) in BNC matrix via ionic gelation method, to develop chitosan nanoparticles-embedded bacterial nanocellulose (CSNPs-BNC) composites. This composite method is simple and efficient, without introducing dispersants and crosslinking agents, while retaining the mechanical properties and native 3D network structure of BNC. The CSNPs-BNC composites had excellent antibacterial activity to support potential clinical application. The CSNPs-BNC composites could promote the adhesion and proliferation of Schwann cells, and demonstrate good biocompatibility both in vitro and in vivo. The results indicated that CSNPs-BNC can provide a promising candidate for biomedical applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Hepatic ischemia reperfusion injury (HIRI) is an important cause of liver dysfunction after liver transplantation for the patients suffered from fatty liver, non-alcoholic cirrhosis, or liver cancer. It is closely related to liver cells apoptosis. Therefore, how to maintain the stable state of cell apoptosis is important to protect the liver from HIRI. Drug treatment basically applies some active substances directly or indirectly, reducing HIRI. But their toxic side effects limit the clinical applications. Differently, non-drug treatment means making use of other kinds of measures to reduce the damage, such as non-pharmaceutical preparations, surgical methods, inhalation or perfusion gas, and so on. Non-drug treatments have been shown to balance cell apoptosis and reduce liver damage during HIRI. This review summarized the progresses in the roles of non-drug treatments on liver cells apoptosis during HIRI in recent years, focusing on apoptosis inducing factors, its signal transduction pathway, and downstream molecules, etc., expecting to elucidate non-drug treatments of anti-HIRI more systematically., (Copyright © 2021. Published by Elsevier Inc.)

Vascular dementia (VaD) is the second most common form of dementia worldwide. It is caused by cerebrovascular disease, and patients often show severe impairments of advanced cognitive abilities. Nitric oxide synthase (NOS) and nitric oxide (NO) play vital roles in the pathogenesis of VaD. The functions of NO are determined by its concentration and bioavailability, which are regulated by NOS activity. The activities of different NOS subtypes in the brain are partitioned. Pathologically, endothelial NOS is inactivated, which causes insufficient NO production and aggravates oxidative stress before inducing cerebrovascular endothelial dysfunction, while neuronal NOS is overactive and can produce excessive NO to cause neurotoxicity. Meanwhile, inflammation stimulates the massive expression of inducible NOS, which also produces excessive NO and then induces neuroinflammation. The vicious circle of these kinds of damage having impacts on each other finally leads to VaD. This review summarizes the roles of the NOS/NO pathway in the pathology of VaD and also proposes some potential therapeutic methods that target this pathway in the hope of inspiring novel ideas for VaD therapeutic approaches.

There are no small-caliber (<6 mm) vascular prostheses so far commercially available around the globe. Bacterial nanocellulose (BNC) is considered a promising material for small-caliber artificial blood vessel applications. Although BNC hydrogel-like (BNC-Gel) materials possess a 3D network structure, facilitating nutrient exchange when used as vascular prostheses, they are difficult to suture during surgery due to their softness. Furthermore, a water content greater than 99% prevents the material from convenient methods of preservation and transport. Air-drying the BNC (BNC-Dry) would solve these problems. The comparative morphology, mechanical properties, hemocompatibility, and cytocompatibility of the BNC-Gel and BNC-Dry conduits of 3 mm in diameter were recorded in the present study, the results indicating that the mechanical properties, hemocompatibility, and cytocompatibility of BNC-Dry conduits were superior to conduits of BNC-Gel. Forty-six days after replacement of the carotid artery in New Zealand white rabbits, the BNC-Dry conduits remained patent. Composite blood vessels composed of cellulose and autologous tissue were harvested for immunohistochemistry and immunofluorescence staining. Sections demonstrated that the outer walls of the conduits were wrapped with autologous tissue. Contractile smooth muscle cells (SMCs) were observed on the outer surface of the conduit, similar to that observed in natural blood vessels. BNC-Dry conduits exhibited excellent performance and possessed properties convenient for surgical applications as small-diameter blood vessels., (Copyright © 2021 Elsevier B.V. All rights reserved.)

BNC was functionalized with collagen (COL) and lactoferrin (LF) to form three different composites: BNC/COL, BNC/LF and BNC/LF/COL using a novel electrophoresis-based technology. The technology is less time-consuming than traditional immersion-adsorption methods and offers the additional advantages of greater protein loading, better homogeneity and a lower requirement for processing solution. Significantly, it has general applicability and great potential for fabricating other similar composites. The water-holding capability and water vapor transmission rate (WVTR) of BNC composites were significantly improved, particularly in the case of BNC/LF/COL, with a WVTR of 2600 g m-2 d-1, indicating that the composite maintains a moderately moist environment over the wound bed, which would enhance epithelial cell migration during the healing process. Compared with BNC and BNC/COL, the LF-impregnated composites mediated a reduction in bacterial viability of at least 77%. Impregnation with COL significantly improved the cytocompatibility of BNC composites to promote the adhesion and proliferation of fibroblast cells. Furthermore, a greater therapeutic effect of BNC/LF/COL was observed in a rat model of wound healing, with a new epithelium formed within 9 days and without any significant adverse reactions. These results suggest that BNC/LF/COL obtained using the electrophoresis method represents a promising wound dressing for use in practical applications.

Bacterial nanocellulose (BNC) is a promising material for small-caliber artificial blood vessels, although promoting its anticoagulant properties with more rapid endothelialization would improve long-term patency. Silk fibroin nanoparticles (SFNP) were introduced into the luminal wall surface of BNC conduits both with and without heparin (Hep) through pressurization followed by fixation. Hep was introduced in two ways: (1) embedded within SF nanoparticles to form SF-HepNPs for construction of the BNC-SF-HepNP conduit and (2) chemically grafted onto BNC and BNC-SFNP to form BNC-Hep and BNC-SFNP-Hep conduits. Fourier transform infrared spectroscopy confirmed the formation of SF-HepNPs, although they did not incorporate into the fibrillar network due to their large size. Hep was successfully grafted onto BNC and BNC-SFNP, verified by toluidine blue staining. The hemocompatibility and cytocompatibility of the five samples (BNC, BNC-SFNP, BNC-SF-HepNP, BNC-Hep, and BNC-SFNP-Hep conduits) were compared in vitro . The heparinized BNC-Hep and BNC-SFNP-Hep conduits improved the anticoagulant properties, and BNC-SFNP-Hep promoted human umbilical vein endothelial cell proliferation but also controlled excessive human arterial smooth muscle cell proliferation, assisting rapid endothelialization and improving lumen patency. No significant inflammatory reaction or material degradation was observed after subcutaneous implantation for 4 weeks. Autogenous tissues were observed around the conduits, and cells infiltrated into the edges of all samples, the BNC-SFNP conduit causing the deepest infiltration, providing an appropriate microenvironment for angiogenesis when used in small-caliber blood vessel applications. Few inflammatory cells were found around the BNC-Hep and BNC-SFNP-Hep conduits. Thus, the anticoagulant properties of the BNC-SFNP-Hep conduit and its stimulation of endothelialization suggest that it has great potential in clinical applications as a small-caliber artificial blood vessel.

Vascular dementia (VaD) is a neurodegenerative disease, with cognitive dysfunction attributable to cerebrovascular factors. At present, it is the second most frequently occurring type of dementia in older adults (after Alzheimer's disease). The underlying etiology of VaD has not been completely elucidated, which limits its management. Currently, there are no approved standard treatments for VaD. The drugs used in VaD are only suitable for symptomatic treatment and cannot prevent or reduce the occurrence and progression of VaD. This review summarizes the current status of pharmacological treatment for VaD, from the perspective of the molecular mechanisms specified in various pathogenic hypotheses, including oxidative stress, the central cholinergic system, neuroinflammation, neuronal apoptosis, and synaptic plasticity. As VaD is a chronic cerebrovascular disease with multifactorial etiology, combined therapy, targeting multiple pathophysiological factors, may be the future trend in VaD., Competing Interests: Declaration of interest The authors declare no conflict of interest., (copyright: © 2021 Kuang et al.)

Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic and chronic synovitis that lead to joint destruction, pain, and many complications. Treatments only relieve certain symptoms, but do not cure RA completely. Prostaglandins (PGs) are lipid signalling molecules and released in the early phase of RA. Increasing evidences have shown five main contribution of PGs to the different stages and symptoms of RA. First, PGs maintain the autoimmune response and immune-system inflammation by modulating the differentiation, maturation, and cytokine production of immune cells. Second, PGs are beneficial for leukocyte infiltration, synovial hyperplasia, and angiogenesis to promote synovitis. Third, PGs are involved in cartilage degradation and bone resorption. Fourth, PGs are important mediators of joint-pain regulation. Finally, in the late stage of RA inflammation, PGs play a part in joint protection. Those findings suggest that PGs are potential therapy targets for RA. This review highlights recent advances in the RA development caused by PGs, and provides recommendations for future research directions.

Earlier electroencephalographic studies have compared attractive and unattractive faces and between faces with other objects, such as flowers, without revealing if a recognition memory bias toward faces and flowers exists or whether humans exhibit enhanced specific components toward all attractive objects or only toward attractive faces. For objects with similar degrees of attractiveness, we sought to determine if the N170, P1, and N250 reflect upon the attractiveness of faces and flowers and demonstrated by comparing event-related potentials of humans' different perceptual mechanisms recognizing high attractive faces and high attractive flowers. The repeated high attractive faces tended to elicit a larger N170. Simultaneously, the P1 was preferentially associated with the repeated high attractive flowers, but both indicated that the repetitive enhancement effect only occurred on repeated attractive faces. Thus, differences existed in the perceptual mechanisms for processing repeated high attractive faces and repeated high attractive flowers. However, there was no significant difference in N250 between repeated faces and repeated flowers or between high attractive faces and high attractive flowers. Consequently, high attractive faces and high attractive flowers capture the beholder's memory bias in different processing stages. The N170 and P1 components are affected by attractiveness, thereby demonstrating the differences between human perceptual mechanisms in recognizing high attractive faces and objects., Competing Interests: The authors declare no conflict of interest., (© 2020 Zhang et al. Published by IMR Press.)

Alginate (Alg) and bacterial nanocellulose (BNC) have exhibited great potential in biomedical applications, especially wound dressing. Non-toxicity and a moisture-maintaining nature are common features making them favorable for functional dressing fabrication. BNC is a natural biopolymer that promotes major advances to the current and future biomedical materials, especially in a flat or tubular membrane form with excellent mechanical strength at hydrated state. The main drawback limiting wide applications of both BNC and Alg is the lack of antibacterial activity, furthermore, the inherent poor mechanical property of Alg leads to the requirement of a secondary dressing in clinical treatment. To fabricate composite dressings with antibacterial activity and better mechanical properties, sodium alginate was efficiently incorporated into the BNC matrix using a time-saving vacuum suction method followed by cross-linking through immersion in separate solutions of six cations (manganese, cobalt, copper, zinc, silver, and cerium). The results showed the fabricated composites had not only pH-responsive antibacterial activities but also improved mechanical properties, which are capable of acting as smart dressings. All composites showed non-toxicity toward fibroblast cells. Rat model evaluation showed the skin wounds covered by the dressings healed faster than by BNC.

A novel design of bioreactor G-BNC, in combination with two previously reported designs of bioreactor were used to fabricate three small caliber bacterial nanocellulose (BNC) conduits (G-BNC, S-BNC and D-BNC). They were compared systematically with a clinically-used ePTFE graft. S-BNC possessed a laminated structure, the lowest BNC content, roughest luminal surface and weakest mechanical properties, and so might not be sufficiently strong for use as an artificial blood vessel alone. The D-BNC conduit possessed an unstratified structure with a fiber network that was more dense and the greatest BNC content, providing the strongest mechanical properties. G-BNC possessed a looser network with the smoothest luminal surface and greater hemocompatibility. Following comprehensive evaluation of mechanical properties and performance, we judge that D-BNC and G-BNC should possess greater potential in application as small caliber vascular grafts, however the patency of the three BNC conduits need be further verified in animal studies in vivo., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is the most common autoimmune disease, resulting in synovitis, joint pain and stiffness, even deformity and disability. The interactions between leukotriene B4 (LTB4) and neutrophils in RA progression have not been elucidated in detail. Our review focuses on the correlation of LTB4 and neutrophils in the development of RA especially in terms of infiltration and delayed life span of neutrophils. In this article, the roles of LTB4 in the anti-apoptosis of neutrophils will be detailed, which is achieved by suppressed pro-apoptotic Bax and up-regulated anti-apoptotic Mcl-1, and several key molecules, as well as signalling pathways and factors relevant to the enhancement of LTB4 production and functions. The mechanisms of LTB4-induced anti-apoptosis and infiltration of neutrophils provide more potential targets in the treatment of RA and recent therapeutic strategies are also discussed.

The timely enumeration of cells of nanocellulose-producing bacteria is challenging due to their unique growth properties. To better understand the metabolism of the bacteria and better control the concentration of living cells during cultivation, a prompt cell counting technology is crucial and urgently required. In this work, two fluorescent dyes, the asymmetrical anthocyanidin dye SYBR Green I (SG) and propidium iodide (PI), were first combined for Komagataeibacter xylinus species to determine live/dead bacterial cells quantitatively and promptly. The number of live and dead K. xylinus cells determined using an epifluorescence microscope corresponded well to the results obtained using a fluorescence microplate reader. The R 2 values were 0.9986 and 0.9920, respectively, and were similar to those obtained with the LIVE/DEAD ® BacLight TM commercial kit. SG/PI double-staining showed proper efficiency in distinguishing live/dead cells for the K. xylinus strain (R 2  = 0.9898). The technology was applied to standardize four different K. xylinus strains, and the initial cell concentration of the strains was precisely controlled (no significant difference among the strains, P> 0.05). The cellulose yield per live cell was calculated, and significant differences (P < 0.05) were found among the four strains in the following order: DHU-ATCC-1> DHU-ZCY-1> DHU-ZGD-1> ATCC 23770. The study shows (i) the application of the SG/PI staining to standardizing inocula for bacterial cellulose production so that a more accurate comparison can be made between different strains, and (ii) the lower cost of using SG rather than the SYTO 9 of the commercially available LIVE/DEAD ® BacLight TM kit., (© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aβ and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aβ and Tau can induce autophagy to promote their clearance by means of mTOR-dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aβ and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi-directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aβ; (c) Aβ and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aβ and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin-1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The development of biodegradable and antibacterial hemostatic materials with high blood absorption to halt the internal hemorrhage of deep noncompressible wounds remains a challenge. In this study, a novel hemostatic nanocomposite (OBC/COL/CS) was fabricated by coupling oxidized bacterial cellulose (OBC) and chitosan (CS) with collagen (COL), that is, during the electrostatic self-assembly of OBC with CS (OBC/CS), COL was ingeniously attached as a functional component by the electrostatic attraction of cationic CS and anionic OBC. The introduction of collagen was anticipated to provide functional properties such as enhanced hemostasis and promotion of wound healing so as to achieve a new functional composite. This study is the first to evaluate the performance of OBC, OBC/CS, and the OBC/COL/CS composite for rapid internal hemostasis using a rat liver injury model. To our knowledge, this is also the first study to report that OBC has a faster biodegradability in vivo than commercial hemostatic oxidized regenerated plant cellulose (ORC). The OBC/COL/CS nanocomposite exhibited appropriate mechanical strength, broad spectrum antimicrobial properties, and excellent biodegradation in vivo. Furthermore, excellent hemostatic efficacy of the composite was confirmed in vivo. OBC/COL/CS exhibited greater procoagulant properties and blood-clotting capability, higher adhesion of erythrocytes and platelets with concomitant lower blood loss, in addition to ultrafast cessation of bleeding, superior to the commercial hemostatic ORC product Surgicel gauze. The results suggest that the OBC/COL/CS is a fast and efficient procoagulant agent with good antibacterial properties and great potential for use as an absorbable hemostat for control of internal bleeding.

Background: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive vasculitis that affects the vessels of the small and medium-sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed., Objective: The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in figures to provide a comparatively complete reference., Methods: We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature)., Results: After screening content of works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further study of relationship was required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role., Conclusion: 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer disease (AD) is characterized as a chronic neurodegenerative disease associated with aging. The clinical manifestations of AD include latent episodes of memory and cognitive impairment, psychiatric symptoms and behavioral disorders, as well as limited activities in daily life. In developed countries, AD is now acknowledged as the third leading cause of death, following cardiovascular disease and cancer. The pathogenesis and mechanism of AD remain unclear, although some theories have been proposed to explain AD, such as the theory of β-amyloid, the theory of the abnormal metabolism of tau protein, the theory of free radical damage, the theory of the inflammatory response, the theory of cholinergic damage, etc. Effective methods to predict, prevent or reverse AD are unavailable, and thus the development of new, efficient therapeutic drugs has become a current research hot spot worldwide. The isolation and extraction of active components from natural drugs have great potential in treating AD. These drugs possess the advantages of multiple targets in multiple pathways, fewer side effects and a long duration of curative effects. This article summaries the latest research progress regarding the mechanisms of natural drugs in the treatment of AD, providing a review of the literature and a theoretical basis for improving the clinical treatment of AD., (Copyright © 2019 Ma, Yang, Li, Yue, Chen, Yang, Huang, Zhu, Hong and Yang.)

Thirteen agitator configurations were investigated at low speed in stirred-tank reactors (STRs) to determine if improved crude bacterial nanocellulose (BNC) productivity can be achieved from glucose-based media while maintaining high BNC quality using Komagataeibacter xylinus ATCC 23770 as a model organism. A comparison of five single impellers showed the pitched blade (large) was the optimal impeller at 300 rpm. The BNC production was further increased by maintaining the pH at 5.0. Among the single helical ribbon and frame impellers and the combined impellers, the twin pitched blade provided the best results. The combined impellers at 150 rpm performed better than the single impellers, and after optimizing the agitation conditions, the twin pitched blade (large) and helical ribbon impellers performed the best at 100 rpm. The performances of different agitators at low speed during BNC production were related to how efficiently the agitators improved the oxygen mass transfer coefficient. The twin pitched blade (large) was verified as providing the optimum performance by an observed crude BNC production of 1.97 g (L×d) -1 and a BNC crude yield of consumed glucose of 0.41 g g -1 , which were 2.25 and 2.37 times higher than the initial values observed using the single impeller respectively. Further characterization indicated that the BNC obtained at 100 rpm from the STR equipped with the optimal agitator maintained high degree of polymerization and crystallinity., (© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Rheumatoid arthritis is a chronic autoimmune disease characterised by unbearable joint pain as well as bone and cartilage destruction. Although RA development is greatly controlled, the pain and bone damage failed to be relieved and managed. Leukotriene B4 (LTB4) has been proved to play an essential role in the induction of pain and bone damage. The nerve injury of RA can promote the production of LTB4, which act on their receptors, leading to the increased release of pro-inflammatory cytokines and ROS to reduce neuron viability and pain threshold. Moreover, LTB4-BLT1 activation can also increase intracellular calcium concentration and neuron excitability as well as NF-κB pathway activation, which further promote the production of MMP-9 and CXC3R-1. The mutual promotion between LTB4 and neutrophil accumulation accelerates the release of TNF-α and IL-β, which enhance both peripheral and central nerve system sensitisation. LTB4 also involve in TrpV1 channel activation and modulation of P2X3 receptor activation. All above mechanisms contribute to the development of RA pain. IL-23, cPLA2 and PI3K increase the production of CD11b+Gr1high myeloid subtype and calcium concentration, which promote the production of LTB4 and further accelerate IL-17 and TNF activation as well as calcium influx to conduce to osteoclastogenesis, resulting in aggregated bone damage. Our review is the first to conclude the signalling pathways and associated molecules in LTB4-induced pain and bone damage.

Komagataeibacter xylinus ATCC 23770 was statically cultivated in eight culture media based on different carbon sources, viz. seven biomass-derived sugars and one sugar mixture. The productivity and quality of the bacterial nanocellulose (BNC) produced in the different media were compared. Highest volumetric productivity, yield on consumed sugar, viscometric degree of polymerization (DP v , 4350-4400) and thermal stability were achieved using media based on glucose or maltose. Growth in media based on xylose, mannose or galactose resulted in lower volumetric productivity and DP v , but in larger fibril diameter and higher crystallinity (76-78%). Growth in medium based on a synthetic sugar mixture resembling the composition of a lignocellulosic hydrolysate promoted BNC productivity and yield, but decreased fibril diameter, DP v , crystallinity and thermal stability. This work shows that volumetric productivity, yield and properties of BNC are highly affected by the carbon source, and indicates how industrially relevant sugar mixtures would affect these characteristics., (© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

The impact of strain selection and culture conditions on bacterial nanocellulose (BNC) productivity and quality was investigated by using four strains, static and agitated cultures, and an initial pH in the range 4-6. With agitation, strain DHU-ATCC-1 displayed highest productivity [1.14 g/(L × d)]. In static cultures, DHU-ZGD-1186 exhibited superior BNC yield on consumed glucose (0.79 g/g), and lowest by-product formation with respect to gluconic acids [≤0.07 g/(L × d)]. By-product formation typically decreased in the order gluconic acid >2-keto-gluconic acid >5-keto-gluconic acid, and was lowest in cultures with high initial pH. The BNC from DHU-ZGD-1186 exhibited higher average viscometric degree of polymerization (DP v ), higher crystallinity index, and higher tear index. In conclusion, both strain selection and cultivation conditions had an impact on BNC productivity and properties. Productivity, DP v , crystallinity, and mechanical strength of BNC from agitated cultures could be similar to or even higher than the corresponding values for static cultures., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway., Main Body: According to the topic, select the search terms 'atherosclerosis,' 'nitric oxide,' 'eNOS,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission'. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level., Conclusions: eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.

Since anisotropic hydrogel membranes have great potential in tissue engineering and bioseparation, the aim of this study was to produce an anisotropic BNC hydrogel membrane for the first time with enhanced BNC productivity by using a newly designed 30-L horizontal rotary drum bioreactor. As compared with the traditional tray static cultivation, the BNC hydrogel from the rotary drum bioreactor showed anisotropic morphology, sparser network, lower dry matter content of 0.16 w/w%, thicker fiber diameter, and lower degree of polymerization that was still 1.8 times higher than cotton, and featured with much higher ultraviolet-visible light transmittance, as well as demonstrated anisotropic tensile properties, lower Young's modulus of 0.23 MPa and compressive modulus of 0.99 kPa. The productivity of dry and wet BNC was enhanced by 1.65 times and 3.73 times, respectively. The proposed technology may not only obtain anisotropic BNC hydrogel membranes with high transparency, but also promote the BNC productivity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)