As antibiotic resistance increases and new drug development lags, the effectiveness of single antibiotics has drastically diminished for clinical infection treatment. The resistance crisis is exacerbated by the swift development and dissemination of Gram-negative bacteria that are extensively drug-resistant (XDR), particularly strains resistant to carbapenems in clinical settings. In this scenario, antibiotic adjuvants play a crucial role in revitalizing existing treatments to combat carbapenem-resistant bacterial infections. In this study, we synthesized ten small molecular antimicrobial peptide mimics and identified antimicrobial peptide mimic 329 (A329), which exhibited a synergistic effect with minocycline (FICI = 0.023), enhancing its efficacy by 4- to 128-fold, and significantly enhanced the antibacterial efficacy of minocycline against carbapenem-resistant Klebsiella pneumoniae (CRKP, 0.015 ≤ FICI ≤0.141), prevented the emergence of minocycline resistance, improved the survival rate of mice, and decreased bacterial load in tissues at 8 + 8 mg/kg. Mechanistic studies revealed that A329 increases bacterial membrane permeability and disrupts the proton-motive force. Additionally, A329 combined with minocycline boosts intracellular minocycline accumulation, induces intracellular production of reactive oxygen species (ROS), and ultimately triggers bacterial death. These findings advised that A329 in combination with minocycline is a potential combination therapy against XDR-associated infections.

Hemicellulose, a complex polysaccharide abundantly found in plant cell walls, has garnered significant attention for its versatile applications in various fields including biomedical, food packaging, environmental, and material sciences. This review systematically explores the composition, extraction methods, and diverse applications of hemicellulose-derived materials. Various extraction techniques such as organic acid, organic base, enzyme-assisted, and hydrothermal methods are discussed in detail, highlighting their efficacy and potential drawbacks. The applications of hemicellulose encompass biodegradable films, edible coatings, advanced hydrogels, and emulsion stabilizers, each offering unique properties suitable for different industrial needs. Current challenges in hemicellulose research include extraction efficiency, scalability of production processes, and optimization of material properties. Opportunities for future research are outlined, emphasizing the exploration of new applications and interdisciplinary approaches to harness the full potential of hemicellulose. This comprehensive review aims to provide valuable insights for researchers and industry professionals interested in utilizing hemicellulose as a sustainable and functional biomaterial.

Traditional antibiotics have made great contributions to human health and animal husbandry since the discovery of penicillin in 1928, but bacterial resistance and drug residues are growing threats to global public health due to the long-term uncontrolled application of antibiotics. There is a critical need to develop new antimicrobial drugs to replace antibiotics. Antimicrobial peptides (AMPs) are distributed in all kingdoms of life, presenting activity against pathogens as well as anticancer, anti-inflammatory, and immunomodulatory activities; consequently, they have prospects as new potential alternatives to antibiotics. Porcine myeloid antimicrobial peptides (PMAPs), the porcine cathelicidin family of AMPs, have been reported in the literature in recent years. PMAPs have become an important research topic due to their strong antibacterial activity. This review focuses on the universal trends in the biochemical parameters, structural characteristics and biological activities of PMAPs.

The protection of current influenza vaccines is limited due to the viral antigenic shifts and antigenic drifts. The universal influenza vaccine is a new hotspot in vaccine research that aims to overcome these problems. Polydopamine (PDA), a versatile biomaterial, has the advantages of an excellent biocompatibility, controllable particle size, and distinctive drug loading approach in drug delivery systems. To enhance the immunogenicities and delivery efficiencies of H9N2 avian influenza virus (AIV) epitope peptide vaccines, PDA nanoparticles conjugated with the BPP-V and BP-IV epitope peptides were used to prepare the nano BPP-V and BP-IV epitope peptide vaccines, respectively. The characteristics of the newly developed epitope peptide vaccines were then evaluated, revealing particle sizes ranging from approximately 240 to 290 nm (PDI<0.3), indicating that the synthesized nanoparticles were stable. Simultaneously, the immunoprotective effects of nano BPP-V and BP-IV epitope peptide vaccines were assessed. The nano BPP-V and BP-IV epitope vaccines, especially nano BP-IV epitope vaccine, quickly induced anti-hemagglutinin (HA) antibody production and a sustained immune response, significantly promoted humoral and cellular immune responses, reduced viral lung damage and provided effective protection against AIV viral infection. Together, these results reveal that PDA, as a delivery carrier, can improve the immunogenicities and delivery efficiencies of H9N2 AIV nano epitope vaccines, thereby providing a theoretical basis for the design and development of PDA as a carrier of new universal influenza vaccines.

Short peptide antigens covering conserved T or B cell epitopes have been investigated in influenza vaccines. Bursal pentapeptide V (BPP-V) and bursal peptide IV (BP-IV) are small molecular peptides that were isolated and identified from the bursa of Fabricius (BF) and induce a strong immune response at both the humoural and cellular levels. To explore the molecular adjuvant potential of BPP-V and BP-IV with an epitope vaccine, an epitope peptide (HA284-298, GNCVVQCQTERGGLN) rich in T and B cell epitopes for the H9N2 avian influenza virus (AIV) haemagglutinin (HA) protein was selected. BPP-V and BP-IV were coupled with the epitope peptide sequence to form BPP-V and BP-IV-epitope vaccines, respectively. The immunoefficacy of BPP-V and BP-IV-epitope peptide vaccines was evaluated. The results showed that the epitope peptide had weak immunogenicity. The BPP-V-epitope peptide vaccine promoted only the secretion of anti-HA IgG and IgG1 antibodies. The BP-IV-epitope peptide vaccine not only promoted the production of anti-HA IgG and IgG1 antibodies but also significantly induced the production of the IgG2a antibody. The BP-IV-epitope peptide vaccine significantly promoted the production of interleukin (IL-4) and interferon-γ (IFN-γ) (the BPP-V epitope peptide vaccine promoted only the production of IL-4), enhanced the cytotoxic T lymphocyte (CTL) response, and increased the proportion of CD3+ T lymphocytes. Moreover, the BP-IV-epitope peptide vaccine promoted a cell-mediated immune response similar to that of the AIV vaccine group. Furthermore, BPP-V and BP-IV-epitope peptide vaccines could also accelerate the clearance of pulmonary virus and reduce pathological damage after the challenge with H9N2 AIV. This study demonstrates the potential of BP-IV as an effective adjuvant for the epitope peptide vaccine for the H9N2 AIV.

抗生素的耐药性和动物源性食品中的药物残留问题严重威胁全球公共卫生系统.因此,开发出不易产生耐药性、抗菌活性高的新型抗菌药物迫在眉睫.抗菌肽因其分子量小、抗菌谱广、不易产生耐药性等优点受到科学家们的广泛关注,但天然抗菌肽具有抗菌活性低、溶血活性和细胞毒性等缺陷.随着抗菌肽序列和结构的不断优化,多种具有显著体内外抗菌活性且安全高效的新型抗菌药物被研发出来.猪源抗菌肽PMAP-36是从猪骨髓细胞中分离出来的一种具有典型两亲性a-螺旋结构的高阳离子抗菌肽.本文就国内外关于猪源抗菌肽PMAP-36的序列设计及其结构优化等方面的研究进展进行综述.

Because of the growing problem of antibiotic resistance, the antibacterial activity of antimicrobial peptides (AMPs) has attracted attention. In this study, two PMAP-GI24 peptide analogs, PMAP-24WW and PMAP-24KK, were synthesized by extending the α-helix and increasing the positive charge of the parental peptide. The antibacterial activities of PMAP-GI24 and its analogs were detected in vitro and in vivo. The results showed that after modification, PMAP-24KK displayed an increased zone of inhibition against Escherichia coli ATCC25922 compared to that of PMAP-GI24. PMAP-24WW had inhibition zones against nine bacterial strains, among which, the antibacterial zones were larger than those of PMAP-GI24 against seven bacterial strains. Furthermore, PMAP-24KK had inhibition zones against ten bacterial strains, and the antibacterial zones were larger than those of PMAP-GI24 against seven bacterial strains. Moreover, in the in vivo efficacy assessment of mice infected with Salmonella enterica serovar choleraesuis C78-1 and Listeria monocytogenes CICC21533, the PMAP-GI24 analogs effectively reduced the number of bacterial and decreased the inflammatory damage in the mouse livers and lungs, thus effectively reducing mortality. This study provides reference data for the clinical design of effective antibiotic alternatives.

Antimicrobial peptides are a new type of antibacterial drugs with a broad antibacterial spectrum. Based on our previous research, PMAP-23RI-Dec was designed by modifying the C-terminal of PMAP-23RI with decanoic acid. In this study, we measured the antibacterial activity, stability, hemolysis, and cytotoxicity of PMAP-23RI-Dec. The mechanism of PMAP-23RI-Dec on biofilm and cell membranes were also studied. The results show that PMAP-23RI-Dec exhibited high antibacterial activity and stability, but the hemolytic activity and cytotoxicity of PMAP-23RI-Dec were not enhanced. Moreover, PMAP-23RI-Dec could inhibit biofilm formation at low concentrations, and enhance the killing effect on bacteria by changing the permeability of their cell membranes. Finally, PMAP-23RI-Dec reduced Pseudomonas aeruginosa GIM1.551 and Staphylococcus aureus ATCC25923 damage to organs, and showed superior efficacy against peritonitis. PMAP-23RI-Dec also reduced the scope of abscess and alleviated wound infections. Our research indicated that PMAP-23RI-Dec is a new antibacterial agent with potential clinical application.

Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW in vitro. Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.

Background The problem of increasing resistance against conventional antibiotics has drawn people’s attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum. Results In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage. Conclusions Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic.

Antimicrobial peptides (AMPs) have gained interesting as a new type of antimicrobial agent. The cathelicidin-derived antimicrobial peptide PMAP-23 has broad-spectrum antibacterial activity, and to improve its antimicrobial activity, we used amino acid substitution at position 5 or 19 of PMAP-23 to design three analogs, named PMAP-23R (Leu5--Arg), PMAP-23I (Thr19--Ile), and PMAP-23RI (Leu5--Arg and Thr19--Ile). We found that the analog peptides exhibited higher stability and improved antibacterial activity compared with PMAP-23. Additionally, the analog peptides PMAP-23I and PMAP-23RI inhibited the growth of Shigella flexneri CICC 21534, whereas PMAP-23 and PMAP-23R exhibited no antibacterial activity against S. flexneri CICC 21534. Moreover, the peptide analogs showed negligible hemolysis and cytotoxicity. We also found that PMAP-23RI exerted impressive therapeutic effects on mice infected with Staphylococcus aureus ATCC 25923 and Salmonella enterica serovar Typhimurium SL1344. PMAP-23RI induced a greater reduction in pathological damage and a higher decrease in the bacterial gene copies in the lung and liver tissues and greatly reduced mouse mortality. In conclusion, the peptide analogs PMAP-23R, PMAP-23I, and PMAP-23RI enhanced the stability and antimicrobial activity of PMAP-23, but PMAP-23RI exhibits more promise as a new antimicrobial agent candidate for the treatment of bacterial infections.

Bacterial resistance induced by the use of antibiotics has provided a chance for the development of antimicrobial peptides (AMPs), and modification of AMPs to enhance the antibacterial activity or stability has become a research focus. PMAP‐37 is an AMP isolated from porcine myeloid marrow, and studies on its modification have not yet been reported. In this study, three PMAP‐37 analogs named PMAP‐37(F9‐R), PMAP‐37(F34‐R), and PMAP‐37(F9/34‐R) were designed by residue substitution to enhance the positive charge. The antimicrobial activity of PMAP‐37 and its analogs in vitro and in vivo were detected. The results showed that compared with PMAP‐37, PMAP‐37(F9‐R) and PMAP‐37(F9/34‐R) exhibited antibacterial activity against S. flexneri CICC21534. Although PMAP‐37(F34‐R) had no antibacterial activity against S. flexneri CICC21534, its minimal inhibitory concentrations (MICs) were significantly lower than those of PMAP‐37 against most bacterial strains. Besides, all PMAP‐37 analogs were pH stable, retaining stable antibacterial activity after treatment with solution from pH 2 to pH 8/9. In addition, the PMAP‐37 analogs displayed increased thermal stability, and PMAP‐37(F34‐R) retained >60% antibacterial activity after boiling for 2 hours. Furthermore, the PMAP‐37 analogs exhibited impressive therapeutic efficacy in bacterial infections by reducing bacterial burden and inflammatory damage in the lung and liver, resulting in a reduction in mortality. Notably, the therapeutic effect of PMAP‐37(F34‐R) was comparable to that of ceftiofur sodium, and even superior to antibiotics in L. monocytogenes CICC21533 infection model. In conclusion, the PMAP‐37(F34‐R) may be a candidate for the treatment of bacterial infections in the clinic.

With increasing resistance against conventional antibiotics, there is an urgent need to discover novel substances to replace antibiotics. This need provides an opportunity for the development of antimicrobial peptides (AMPs). To develop new AMPs with effective and safe therapeutic effects, two PMAP-37 analogs called PMAP-37(R13-I) and PMAP-37(K20/27-I) were designed to increase hydrophobicity. Antimicrobial susceptibility testing and animal infection models were used to assess their antibacterial activity. The results showed that the minimal inhibitory concentrations of PMAP-37(R13-I) were lower than those of PMAP-37 for two gram-negative strains. Compared with PMAP-37, PMAP-37(K20/27-I) not only inhibited the growth of most bacterial strains, but also exhibited antibacterial activity against Shigella flexneri CICC21534. In addition, PMAP-37(K20/27-I) exhibited pH and thermal stability. PMAP-37(R13-I) had a therapeutic effect only in mice infected with Salmonella typhimurium SL1344. However, PMAP-37(K20/27-I) exhibited the therapeutic effects, whether in the clinical symptoms, the tissue lesions, or the tissue bacterial loads and the survival rates in mice infected with Staphylococcus aureus ATCC25923 or S. typhimurium SL1344. Therefore, PMAP-37(K20/27-I) can be used as a substitute for antibiotics against infection with bacterial strains.

The growing problem of antibiotic resistance has attracted people's attention; thus, the search for new antibacterial agents is imminent. In this study, a series of antimicrobial peptides (AMPs) based on the porcine antibacterial peptide PMAP-36 were designed by amino acid substitution to develop peptide analogues as new classes of antimicrobial agents. By extending the α-helix and increasing the positive charge, two peptide analogues, PMAP-36PW and PMAP-36PK, were synthesized. The antibacterial activities of PMAP-36 and its peptide analogues were detected in vitro and in vivo. The results showed that PMAP-36PW and PMAP-36PK had a broadened antibacterial spectrum compared to that of PMAP-36. After the modification, PMAP-36PW and PMAP-36PK exhibited antibacterial activities on swine Escherichia coli K88, while PMAP-36 did not. PMAP-36, PMAP-36PW and PMAP-36PK did not have antibacterial activities against Enterococcus faecium B21. PMAP-36 PW had significant antibacterial activity against seven bacterial strains compared to PMAP-36, and PMAP-36PK had significant antibacterial activity against five bacterial strains compared to PMAP-36. Furthermore, PMAP-36PW exhibited enhanced pH stability. Moreover, in the in vivo efficacy assessment of mice infected with Salmonella choleraesuis C78-1 and Listeria monocytogenes CICC 21533, the peptide analogues exhibited an impressive therapeutic effect by reducing bacterial gene copies and decreasing inflammatory damage in mouse livers and lungs, resulting in a reduction in mouse mortality. This study provides reference data for the design of clinically effective antibacterial peptides.

BACKGROUND Bursal Pentapeptide (BPP)-(III-V) are peptides isolated from the Bursa of Fabricius (BF). METHOD The peptides' adjuvant activities were evaluated in mice immunized with the H9N2 avian influenza vaccine. RESULTS The results showed that BPP-IV did not promote humoral or cellular immune responses. BPP-III had no effect on antibody production, but increased populations of CD3+ and CD8+ T cells, CTL levels and proliferation activities of splenic T-lymphocytes. BPP-V increased the level of antibodies (HI, IgG and its subtype IgG1) and the cytokine IL-4, as well as the ratio of CD3+ T cells and its subsets CD4+ and CD8+ T cells, BPP-V also increased CTL level and promoted the proliferation activity of T- and B-lymphocyte. Furthermore, in animal challenge experiment, BPP-III and BPP-V reduced viral RNA copies and viral titers, and reduced inflammatory cell infiltration. CONCLUSION In summary, BPP-IV did not have an effect on specific immune responses, therefore it could not reduce pathological damage in mice lungs; BPP-III provided resistance to the antigen through the cell-mediated immune response; BPP-V enhanced both humoral and cellular immune responses, therefore provided protections against the H9N2 Avian Influenza Virus (AIV). Altogether, BPP-III and BPP-V could be adjuvant candidates for the H9N2 avian influenza vaccine.

The bursa of Fabricius (BF) is a central humoral immune organ unique to birds. Four bursal peptides (BP-I, BP-II, BP-III, and BP-IV) have been isolated and identified from the BF. In this study, the immunoadjuvant activities of BPs I to IV were examined in mice immunized with H9N2 avian influenza virus (AIV) vaccine. The results suggested that BP-I effectively enhanced cell-mediated immune responses, increased the secretion of Th1 (interferon gamma)- and Th2 (interleukin-4)-type cytokines, and induced an improved cytotoxic T-lymphocyte (CTL) response to the H9N2 virus. BP-II mainly elevated specific antibody production, especially neutralizing antibodies, and increased Th1- and Th2-type cytokine secretion. BP-III had no significant effect on antibody production or cell-mediated immune responses compared to those in the control group. A strong immune response at both the humoral and cellular levels was induced by BP-IV. Furthermore, a virus challenge experiment followed by H&E staining revealed that BP-I and BP-II promoted removal of the virus and conferred protection in mouse lungs. BP-IV significantly reduced viral titers and histopathological changes and contributed to protection against H9N2 AIV challenge in mouse lungs. This study further elucidated the immunoadjuvant activities of BPs I to IV, providing a novel insight into immunoadjuvants for use in vaccine design.

法氏囊活性肽BP-I是从法氏囊组织中新分离出的活性肽,其免疫学功能尚不清晰.为了研究法氏囊活性肽BP-I的免疫佐剂特性,本试验将法氏囊活性肽BP-I联合H9N2型禽流感病毒(Avian influenza virus,AIV)灭活疫苗免疫小鼠,检测免疫后小鼠的IgG抗体和细胞因子(IL-4和IFN-γ)的分泌水平,并通过动物免疫保护试验来评价其对小鼠的免疫保护作用.本试验将80只小鼠随机分组,分别为PBS组,疫苗组,疫苗+BP-I组,空白组,每组20只.对小鼠进行两次免疫,结果显示,法氏囊活性肽BP-I联合禽流感H9N2灭活疫苗使用能够增加小鼠机体中IgG抗体的含量,提高细胞因子IFN-γ的分泌水平,对IL-4的分泌水平影响不大,表明法氏囊活性肽BP-I联合疫苗既能增强机体体液免疫应答,又能增强细胞免疫应答.动物免疫保护试验结果显示,疫苗+肽组小鼠肺脏的病变程度减轻,法氏囊活性肽BP-I联合疫苗使用有助于小鼠肺脏中H9N2型禽流感病毒的清除.结果表明,法氏囊活性肽BP-I具有良好的免疫佐剂的潜能,为进一步研究开发新型疫苗佐剂奠定了基础.

BACKGROUND:To study the anti-SARS virus activities of different recombinant human interferons on the cell culture system.METHODS:Anti-SARS virus activities of interferons were determined by using CPE inhibition test in human skeletal muscle sarcoma (Rda) cell culture.RESULTS:The average minimum amount of interferon alpha 2b, alpha 1b, beta 1b or omega 1b to inhibit 50% CPE in Rda cell culture was (160.5+/-129.5) IU/ml, (149.0+/-71.7) IU/ml, (69.5+/-61.5) IU/ml, (87.3+/-47.1) IU/ml, respectively or (0.6+/-0.5) ng/ml, (10.6+/-5.1) ng/ml, (3.5+/-3.1) ng/ml, (0.9+/-0.5) ng/ml, respectively.CONCLUSION:All the tested recombinant interferons showed anti-SARS virus activities on the Rda cell culture with different sensitivities.