Recent progress in mesenchymal stem cell-based therapy for acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases in critically ill patients. Although pathophysiology of ALI/ARDS has been investigated in many studies, effective therapeutic strategies are still limited. Mesenchymal stem cell (MSC)-based therapy is emerging as a promising therapeutic intervention for patients with ALI. During the last two decades, researchers have focused on the efficacy and mechanism of MSC application in ALI animal models. MSC derived from variant resources exhibited therapeutic effects in preclinical studies of ALI with different mechanisms. Based on this, clinical studies on MSC treatment in ALI/ARDS has been tried recently, especially in COVID-19 caused lung injury. Emerging clinical trials of MSCs in treating COVID-19-related conditions have been registered in past two years. The advantages and potential of MSCs in the defense against COVID-19-related ALI or ARDS have been confirmed. This review provides a brief overview of recent research progress in MSC-based therapies in preclinical study and clinical trials in ALI treatment, as well as the underlying mechanisms.

Cancer risk following surgical removal of tonsils and adenoids - a population-based, sibling-controlled cohort study in Sweden.

BACKGROUND: Removal of tonsils and adenoids is among the most common surgical procedures worldwide. Evidence of increased risk of cancer following such surgery is, however, inconclusive. METHODS: We conducted a population-based, sibling-controlled cohort study of 4,953,583 individuals in Sweden with a follow-up during 1980-2016. History of tonsillectomy, adenotonsillectomy, and adenoidectomy was identified from the Swedish Patient Register whereas incident cases of cancer during follow-up were identified from the Swedish Cancer Register. We used Cox models to calculate hazard ratios (HR) with 95% confidence intervals (CI) of cancer in both a population and a sibling comparison. The sibling comparison was used to assess the potential impact of familial confounding, due to shared genetic or non-genetic factors within a family. RESULTS: We found a modestly increased risk for any cancer following tonsillectomy, adenoidectomy, or adenotonsillectomy in both the population (HR 1.10; 95%CI 1.07-1.12) and sibling (HR 1.15; 95%CI 1.10-1.20) comparisons. The association did not differ greatly by type of surgery, age at surgery, or potential indication for surgery, and persisted more than two decades after surgery. An excess risk was consistently observed for cancer of the breast, prostate, thyroid, and for lymphoma in both population and sibling comparisons. A positive association was observed for pancreatic cancer, kidney cancer, and leukemia in the population comparison whereas a positive association was observed for esophageal cancer in the sibling comparison. CONCLUSIONS: Surgical removal of tonsils and adenoids is associated with a modestly increased risk of cancer during the decades following the surgery. The association is unlikely attributed to confounding due to shared genetic or non-genetic factors with a family.

Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis.

A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC50 values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 µg/mL, respectively, whereas the LC50 value of MA was 659.34 µg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 µg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.

Investigating material basis and molecular mechanism of Qing Cuo formula in the treatment of acne based on animal experiments, UPLC-LTQ-Orbitrap-MS and network pharmacology.

CONTEXT: Qing Cuo Formula (QCF) is a traditional Chinese medicine for treating acne, but its active compounds and molecular mechanisms are unclear. OBJECTIVE: To investigate the material basis and molecular mechanism of QCF. MATERIALS AND METHODS: In vivo experiments were conducted on 60 male golden hamsters with damp-heat acne, with a blank group, a spironolactone group and 3 QCF administration groups (given high, medium and low doses) over a 30-day period. Serum androgen and inflammatory cytokine levels were tested by ELISA. In vitro, chemical compositions of QCF were investigated by UPLC-LTQ-Orbitrap-MS. Network pharmacology approaches were used to analyse the protein-protein interaction (PPI) network and QCF active compounds-intersection targets-acne network. GO enrichment and KEGG pathway analysis was conducted subsequently. RESULTS: Low-dose QCF group (11.4 g/kg/day) showed significantly reduced levels of serum T (4.94 ± 0.36; 5.51 ± 0.36 ng/mL), DHT (6.67 ± 0.61; 8.09 ± 0.59 nmol/L), E2 (209.01 ± 20.92; 237.08 ± 13.94 pg/mL), IL-1α (36.84 ± 3.23; 44.07 ± 4.00 pg/mL) and FFA (128.32 ± 10.94; 148.00 ± 12.12 µmol/L) compared to the blank group (p < 0.05). In vitro experiments identified 75 compounds in QCF decoction, with 27 active compounds absorbed in serum. Network pharmacology identified 6 active components connecting 17 targets. GO enrichment and KEGG pathway analysis indicated that QCF's anti-acne targets mainly regulate extracellular matrix function, inflammatory processes, immune response and endocrine function. CONCLUSIONS: This study provides evidence of the molecular mechanism and material basis of QCF in treating androgen-related damp-heat acne, paving the way for further research on its potential in treating other conditions related to damp-heat constitution.

Novel 18ß-glycyrrhetinic acid derivatives as a Two-in-One agent with potent antimicrobial and anti-inflammatory activity.

18ß-glycyrrhetinic acid (GA) is a well-known natural compound of oleanane-type triterpene and is found possessing antimicrobial and anti-inflammatory properties. Nonetheless, its relatively low bioactivity restricts its potential in pharmaceutical applications. To maximize the potential use of this natural herbal compound as antimicrobial and anti-inflammatory agents, the rational modification of GA to enhance its pharmacological activity with low toxicity and to understand the mechanism of action is critically essential. We reported herein the design and synthesis of a series of new GA derivatives. The antimicrobial activities of these new compounds were evaluated by inhibition zone test and minimum inhibitory concentration (MIC) assay. In addition, the anti-inflammatory activity was evaluated by LPS induced BV2 cells inflammation model and 12-O-tetradecanoyl phorbol-13-acetate (TPA) induced ear inflammation mice model. It was found that the derivatives functionalized with a di-substituted phenyl group at the 2-position of GA generally displayed high antimicrobial activity against Gram-positive bacteria (MIC down to 2.5 µM) and potent anti-inflammatory effects (inhibition of NO production up to 55%, comparable to dexamethasone). The in vitro and in vivo results also showed that GA-O-02 and GA-O-06 exert their anti-inflammatory activities through downregulation of NO, pro-inflammatory cytokines and chemokines (IL-1ß, IL-6, IL-12, TNF-α, MCP-1 and MIP-1α) and upregulation of anti-inflammatory cytokines (IL-10). The anti-inflammatory mechanism may involve the inhibition of NF-κB, MAPKs and PI3K/Akt related inflammatory signaling pathways and activation of Nrf2/HO-1 signaling pathway. The results demonstrated that GA-O-02 and GA-O-06 possess great application potential as potent antimicrobial and anti-inflammatory agents.

Tranexamic acid usage in hip fracture surgery: a meta-analysis and meta-regression analysis of current practice.

INTRODUCTION: The use of tranexamic acid (TXA) in hip fracture surgery remains inconclusive. The aim of the present meta-analysis was to assess the role of TXA use in hip fracture surgery, and attempt to disclose possible factors which might influence TXA efficacy and safety. MATERIALS AND METHODS: A systematic computerized literature search was conducted to retrieve all randomized controlled trials (RCTs) and cohort studies regarding TXA use in hip fracture surgery. Overall efficacy and safety were evaluated. Then, subgroup and meta-regression analyses were conducted to disclose the influence of geographic area, fracture type, administration route, frequency and dosage of TXA, blood transfusion threshold, and follow-up duration on the overall effect. RESULTS: Thirty-four RCTs and 11 cohort studies were included. Patients receiving TXA had a significant decrease in the need for blood transfusion, reduced total, intra-operative and post-operative blood loss, a decrease in pre- and postoperative hemoglobin difference, without increasing thromboembolic events risk. Subgroup analysis showed that topical TXA had a lower transfusion rate compared with controls, yet the result did not reach statistical significance. Also, TXA had similar efficacy and safety profiles in patients with different frequency and dosage of TXA. CONCLUSION: Current evidence indicated that intravenous administration of TXA could significantly reduce blood transfusion and blood loss without increasing risk of thromboembolic events. The frequency and dosage of TXA might not alter the beneficial effect. The application of topical TXA should be cautious.

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents.

A series of ursolic acid (UA), oleanolic acid (OA) and 18ß-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25-5 µmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.

Soil resource heterogeneity competitively favors an invasive clonal plant over a native one.

Soil resource heterogeneity can affect plant growth and competitive ability. However, little is known about how soil resource heterogeneity affects competitive interactions between invasive and native plants. We conducted an experiment with an invasive clonal plant Alternanthera philoxeroides and a coexisting native one Alternanthera sessilis. The experiment was a randomized design with three factors, i.e. two species (A. philoxeroides and A. sessilis), two interspecific competition treatments (with and without) and five soil treatments (three homogeneous treatments and two small-scale heterogeneous treatments consisting of two patches of 10 cm × 15 cm and with different initial planting positions). Irrespective of competition, increasing soil resource availability increased the growth of A. philoxeroides. Increasing soil resource availability also increased the growth of A. sessilis without competition, but had no impact with competition. Irrespective of competition, soil resource heterogeneity increased biomass and ramet production of A. philoxeroides, and such effects were independent of initial planting position. For A. sessilis, however, soil resource heterogeneity only increased ramet production when the initial plant was grown in the low-resource patch without competition. Our results suggest that both high soil resource availability and small-scale soil resource heterogeneity can increase the relative competitive ability of the invasive plant A. philoxeroides when grown with its native congener A. sessilis. These findings may partly explain the invasion success of this clonal species in area with high soil resource availability and heterogeneity caused by e.g. nitrogen deposition, fertilization and disturbance.

Economical production of isomaltulose from agricultural residues in a system with sucrose isomerase displayed on Bacillus subtilis spores.

A safe, efficient, environmentally friendly process for producing isomaltulose is needed. Here, the biocatalyst, sucrose isomerase (SIase) from Erwinia rhapontici NX-5, displayed on the surface of Bacillus subtilis 168 spores (food-grade strain) was applied for isomaltulose production. The anchored SIase showed relatively high bioactivity, suggesting that the surface display system using CotX as the anchoring protein was successful. The stability of the anchored SIase was also significantly better. Thermal stability analysis showed that 80% of relative activity was retained after incubation at 40 °C and 45 °C for 60 min. To develop an economical industrial fermentation medium, untreated beet molasses (30 g/L) and cold-pressed soybean powder (50 g/L) were utilised as the main broth components for SIase pilot-scale production. Under the optimal conditions, the productive spores converted 92% of sucrose after 6 h and the conversion rate was 45% after six cycles. Isomaltulose production with this system using the agricultural residues, untreated beet molasses and soybean powder, as substrates is cost-effective and environmentally friendly and can help to overcome issues due to the genetic background.

Recent advances in the biotechnological production of microbial poly(ɛ-L-lysine) and understanding of its biosynthetic mechanism.

Poly(ɛ-L-lysine) (ɛ-PL) is an unusual biopolymer composed of L-lysine connected between α-carboxyl and ɛ-amino groups. It has been used as a preservative in food and cosmetics industries, drug carrier in medicines, and gene carrier in gene therapy. Modern biotechnology has significantly improved the synthetic efficiency of this novel homopoly(amino acid) on an industrial scale and has expanded its industrial applications. In the latest years, studies have focused on the biotechnological production and understanding the biosynthetic mechanism of microbial ɛ-PL. Herein, this review focuses on the current trends and future perspectives of microbial ɛ-PL. Information on the screening of ɛ-PL-producing strains, fermentative production of ɛ-PL, breeding of high-ɛ-PL-producing strains, genomic data of ɛ-PL-producing strains, biosynthetic mechanism of microbial ɛ-PL, and the control of molecular weight of microbial ɛ-PL is included. This review will contribute to the development of this novel homopoly(amino acid) and serve as a basis of studies on other biopolymers.

L-Ribose isomerase and mannose-6-phosphate isomerase: properties and applications for L-ribose production.

L-Ribose is a synthetic L-form monosaccharide. It is a building block of many novel nucleotide analog anti-viral drugs. Bio-production of L-ribose relies on a two-step reaction: (i) conversion of L-arabinose to L-ribulose by the catalytic action of L-arabinose isomerase (L-AI) and (ii) conversion of L-ribulose to L-ribose by the catalytic action of L-ribose isomerase (L-RI, EC 5.3.1.B3) or mannose-6-phosphate isomerase (MPI, EC 5.3.1.8, alternately named as phosphomannose isomerase). Between the two enzymes, L-RI is a rare enzyme that was discovered in 1996 by Professor Izumori's group, whereas MPI is an essential enzyme in metabolic pathways in humans and microorganisms. Recent studies have focused on their potentials for industrial production of L-ribose. This review summarizes the applications of L-RI and MPI for L-ribose production.

In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae.

Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence), as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC10. Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time- and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development.

L-Arabinose isomerase and its use for biotechnological production of rare sugars.

L-Arabinose isomerase (AI), a key enzyme in the microbial pentose phosphate pathway, has been regarded as an important biological catalyst in rare sugar production. This enzyme could isomerize L-arabinose into L-ribulose, as well as D-galactose into D-tagatose. Both the two monosaccharides show excellent commercial values in food and pharmaceutical industries. With the identification of novel AI family members, some of them have exhibited remarkable potential in industrial applications. The biological production processes for D-tagatose and L-ribose (or L-ribulose) using AI have been developed and improved in recent years. Meanwhile, protein engineering techniques involving rational design has effectively enhanced the catalytic properties of various AIs. Moreover, the crystal structure of AI has been disclosed, which sheds light on the understanding of AI structure and catalytic mechanism at molecular levels. This article reports recent developments in (i) novel AI screening, (ii) AI-mediated rare sugar production processes, (iii) molecular modification of AI, and (iv) structural biology study of AI. Based on previous reports, an analysis of the future development has also been initiated.

The stimulatory effect of different CpG oligonucleotides on the maturation of chicken bone marrow-derived dendritic cells.

CpG oligonucleotide (CpG-ODN) can exert an immunostimulatory effect on different types of immune cells such as dendritic cells (DC). The immunostimulatory activity of CpG-ODN is closely related to its nucleotide sequence and structural characteristics. In this study, we aimed at evaluating the stimulatory effects of different CpG-ODN on the maturation of chicken bone marrow-derived DC (BM-DC) in vitro. First, 4 CpG-ODN were designed. Then chicken bone marrow cells were extracted from tibia and femur and cultured in the RPMI 1640 medium with recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. After culture for 6 d, the cells were stimulated by different CpG-ODN or lipopolysaccharide for 24 h. Finally, the effects of different CpG-ODN on the maturation of chicken BM-DC were investigated by morphologic, phenotypic, and functional assays. The results showed that the cultured cells could display the typical DC morphology, and the CpG-ODN could efficiently stimulate the BM-DC to show the mature morphologic characteristics and upregulate the expression of cluster of differentiation (CD) 40 and CD86 molecules. In addition, after stimulation by CpG-ODN, the BM-DC could significantly induce T-cell proliferative response (P < 0.01). Among all the sequences, the stimulatory effect of CpG-ODN F3 with an addition of poly-guanosine strings at the 3' end was the best on the chicken BM-DC. In conclusion, this is the first report to demonstrate that different CpG-ODN have distinct stimulatory effects on the maturation of chicken BM-DC and CpG-ODN F3 with the best stimulatory effect can be a potent stimulant for the maturation of chicken BM-DC.

Effects of migratory birds activities on the stoichiometry of soil carbon, nitrogen and phosphorus in a Carex-dominated wetland of Poyang Lake.

Studying the stoichiometric characteristics of soil nutrients aids in evaluating soil quality and deciphering the coupling of soil nutrients. The influence of migratory bird activities on the dynamics of wetland soil nutrients and their stoichiometric remains unclear. We classified the central, peripheral and adjacent natural grassy areas as severe, mild, and no bird activity (control), respectively, in Donghu Carex meadow, a representative migratory bird habitat in Poyang Lake, based on flock characteristics and initial surveys. We analyzed the contents and stoichio-metry of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) across soil depths of 0-100 cm under different intensities of migratory bird activities. The results showed that the activities of migratory birds significantly impacted nutrient levels exclusively within 0-30 cm soil. Mild activities markedly enhanced SOC and TN across 0-30 cm soil, while both mild and severe activities significantly raised TP within the same depth. For the 0-100 cm soil profiles, soil C/N ratios were 10.0, 10.8, and 9.9, C/P ratios were 23.5, 30.0, and 22.7, and N/P ratios were 2.3, 2.7, and 2.3 under no, mild, and severe bird activities, respectively. Further, mild activities of migratory birds significantly increased soil C/N, C/P and N/P ratios only within the 0-30 cm depth, while the stoichiometric ratios of all soil layer had no significant difference under severe bird activity. Soil stoichiometric ratios strongly correlated with physicochemical properties. SOC, TN, and TP primarily mediated the effects of migratory bird activity on soil carbon, nitrogen, and phosphorus stoichiometric ratios in Poyang Lake wetland. In conclusion, the influence of migratory bird activity on the stoichiometric ratios of soil carbon, nitrogen, and phosphorus in Poyang Lake wetland exhibited depth threshold (approximately 30 cm), aligning with the "Intermediate Distur-bance Hypothesis". These findings could provide a new perspective for the protection of wetlands and migratory birds.

ATG5-mediated keratinocyte ferroptosis promotes M1 polarization of macrophages to aggravate UVB-induced skin inflammation.

Autophagy participates in the regulation of ferroptosis. Among numerous autophagy-related genes (ATGs), ATG5 plays a pivotal role in ferroptosis. However, how ATG5-mediated ferroptosis functions in UVB-induced skin inflammation is still unclear. In this study, we unveil that the core ferroptosis inhibitor GPX4 is significantly decreased in human skin tissue exposed to sunlight. We report that ATG5 deletion in mouse keratinocytes strongly protects against UVB-induced keratinocyte ferroptosis and skin inflammation. Mechanistically, ATG5 promotes the autophagy-dependent degradation of GPX4 in UVB-exposed keratinocytes, which leads to UVB-induced keratinocyte ferroptosis. Furthermore, we find that IFN-γ secreted by ferroptotic keratinocytes facilitates the M1 polarization of macrophages, which results in the exacerbation of UVB-induced skin inflammation. Together, our data indicate that ATG5 exacerbates UVB-induced keratinocyte ferroptosis in the epidermis, which subsequently gives rise to the secretion of IFN-γ and M1 polarization. Our study provides novel evidence that targeting ATG5 may serve as a potential therapeutic strategy for the amelioration of UVB-caused skin damage.

An oxidoreduction potential shift control strategy for high purity propionic acid production by Propionibacterium freudenreichii CCTCC M207015 with glycerol as sole carbon source.

The effects of oxidoreduction potential (ORP) regulation on the process of propionic acid production by Propionibacterium freudenreichii CCTCC M207015 have been investigated. Potassium ferricyanide and sodium borohydride were determined as ORP control agents through serum bottle experiment. In batch fermentation, cell growth, propionic acid and by-products distribution were changed with ORP levels in the range of 0-160 mV. Based on these analysis results, an ORP-shift control strategy was proposed: at first 156 h, ORP was controlled at 120 mV to obtain higher cell growth rate and propionic acid formation rate, and then it was shifted to 80 mV after 156 h to maintain the higher propionic acid formation rate. By applying this strategy, the optimal parameters were obtained as follows: the propionic acid concentration 45.99 g L(-1), productivity 0.192 g L(-1) h(-1), the proportion of propionic acid to total organic acids 92.26 % (w/w) and glycerol conversion efficiency 76.65 %. The mechanism of ORP regulation was discussed by the ratio of NADH/NAD(+), ATP levels, and metabolic flux analysis. The results suggest that it is possible to redistribute energy and metabolic fluxes by the ORP-shift control strategy, and the strategy could provide a simple and efficient tool to realize high purity propionic acid production with glycerol as carbon source.

Comparison of 3 kinds of Toll-like receptor ligands for inactivated avian H5N1 influenza virus intranasal immunization in chicken.

To evaluate the effects of co-administration of inactivated avian influenza H5N1 virus (IAIV) and different Toll-like receptor (TLR) ligands in chickens, 10-d-old chickens were immunized intranasally with IAIV and TLR ligand [Bacillus subtilis spores, polyinosinic-polycytidylic acid, and CpG oligodeoxynucleotides (CpG-ODN), respectively]. The results showed that both anti-avian influenza virus (AIV) specific secretory IgA level in respiratory tract and anti-AIV specific IgG level in serum significantly increased, as well as the expressions of IL-12, interferon-γ, IL-6, and TLR in the nasal cavity and trachea after intranasal immunization with IAIV and TLR ligand. Among the used TLR ligands, B. subtilis spores as the adjuvant for nasal IAIV had the strongest effect on the expression of IL-6 and IL-12 (P < 0.01), whereas the CpG-ODN could present an advantageous effect on the induction of anti-AIV specific IgG and neutralization antibodies (P < 0.01). The chickens that were previously co-administrated with IAIV and B. subtilis spores could survive at an improved rate upon challenge by live AIV H5N1 virus. Our study suggested that B. subtilis spores, polyinosinic-polycytidylic acid, or CpG-ODN all could effectively enhance the local and systemic immune responses to IAIV in chickens. Considering of the effects and cost of these TLR ligands, we prospected that B. subtilis spores might serve as a more affordable and efficacious mucosal adjuvant for nasal IAIV in chickens.

Effects of different CpG oligodeoxynucleotides with inactivated avian H5N1 influenza virus on mucosal immunity of chickens.

Oligodeoxynucleotide containing unmethylated CpG motifs (CpG-ODN) has been proved to be a potent and safe vaccine adjuvant. However, the application of CpG-ODN in poultry vaccines was limited because of its high cost to benefit ratio. The objective of this study was to identify the CpG-ODN with efficient adjuvant activity and low cost in chickens. Four sequences of CpG-ODN were designed based on CpG-ODN 2006, which was used as a template and positive sequence in our study. In the current study, in vitro observations revealed that the designed CpG-ODN had efficient immunostimulatory effects on chicken splenic lymphocytes. The in vivo results showed that the mRNA expressions of IL-6, IL-12, interferon-γ, and Toll-like receptor (TLR) 21 in upper respiratory tract tissues increased significantly in the early period after intranasal immunization with inactivated avian H5N1 influenza virus (IAIV) and CpG-ODN (P < 0.01). In addition, the avian influenza virus (AIV)-specific secretory IgA antibody level in the lavage fluid of upper respiratory tract increased significantly after intranasal immunization with IAIV and CpG-ODN, so did AIV-specific IgG in serum (P < 0.01). Among all the designed CpG-ODN, CpG-ODN F3 with an addition of poly-guanosine strings at the 3'-end not only had the best enhancement on local mucosal immune response but also showed an effective induction of systemic immune response. Most importantly, the virus challenge study showed that prior administration of IAIV with CpG-ODN F3 could protect chickens effectively against live AIV H5N1 challenge. Additionally, among all the CpG-ODN in our study, the cost of the designed CpG-ODN F3 was the lowest because of the partially phosphorothioate backbone. Therefore, we speculated that CpG-ODN F3 with efficient adjuvant activity and a big cost advantage over CpG-ODN F1 (CpG-ODN 2006) might serve as an efficient and affordable nasal adjuvant for inactivated AIV vaccine in chicken.

Lipid metabolism reprogramming in head and neck cancer.

Lipid metabolism reprogramming is one of the most prominent metabolic anomalies in cancer, wherein cancer cells undergo dysregulation of lipid metabolism to acquire adequate energy, cell membrane building blocks, as well as signaling molecules essential for cell proliferation, survival, invasion, and metastasis. These adaptations enable cancer cells to effectively respond to challenges posed by the tumor microenvironment, leading to cancer therapy resistance and poor cancer prognosis. Head and neck cancer, ranking as the seventh most prevalent cancer, exhibits numerous abnormalities in lipid metabolism. Nevertheless, the precise role of lipid metabolic rewiring in head and neck cancer remains unclear. In line with the LIPID MAPS Lipid Classification System and cancer risk factors, the present review delves into the dysregulated molecules and pathways participating in the process of lipid uptake, biosynthesis, transportation, and catabolism. We also present an overview of the latest advancements in understanding alterations in lipid metabolism and how they intersect with the carcinogenesis, development, treatment, and prognosis of head and neck cancer. By shedding light on the significance of metabolic therapy, we aspire to improve the overall prognosis and treatment outcomes of head and neck cancer patients.