Combating bacterial infections with host defense peptides: Shifting focus from bacteria to host immunity.

The increasing prevalence of multidrug-resistant bacterial infections necessitates the exploration of novel paradigms for anti-infective therapy. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), have garnered extensive recognition as immunomodulatory molecules that leverage natural host mechanisms to enhance therapeutic benefits. The unique immune mechanism exhibited by certain HDPs that involves self-assembly into supramolecular nanonets capable of inducing bacterial agglutination and entrapping is significantly important. This process effectively prevents microbial invasion and subsequent dissemination and significantly mitigates selective pressure for the evolution of microbial resistance, highlighting the potential of HDP-based antimicrobial therapy. Recent advancements in this field have focused on developing bio-responsive materials in the form of supramolecular nanonets. A comprehensive overview of the immunomodulatory and bacteria-agglutinating activities of HDPs, along with a discussion on optimization strategies for synthetic derivatives, is presented in this article. These optimized derivatives exhibit improved biological properties and therapeutic potential, making them suitable for future clinical applications as effective anti-infective therapeutics.

Biomimetic Peptide Nanonets: Exploiting Bacterial Entrapment and Macrophage Rerousing for Combatting Infections.

The alarming rise in global antimicrobial resistance underscores the urgent need for effective antibacterial drugs. Drawing inspiration from the bacterial-entrapment mechanism of human defensin 6, we have fabricated biomimetic peptide nanonets composed of multiple functional fragments for bacterial eradication. These biomimetic peptide nanonets are designed to address antimicrobial resistance challenges through a dual-approach strategy. First, the resulting nanofibrous networks trap bacteria and subsequently kill them by loosening the membrane structure, dissipating proton motive force, and causing multiple metabolic perturbations. Second, these trapped bacterial clusters reactivate macrophages to scavenge bacteria through enhanced chemotaxis and phagocytosis via the PI3K-AKT signaling pathway and ECM-receptor interaction. In vivo results have proven that treatment with biomimetic peptide nanonets can alleviate systemic bacterial infections without causing noticeable systemic toxicity. As anticipated, the proposed strategy can address stubborn infections by entrapping bacteria and awakening antibacterial immune responses. This approach might serve as a guide for the design of bioinspired materials for future clinical applications.

Gut-Derived Metabolites from Dietary Tryptophan Supplementation Quench Intestinal Inflammation through the AMPK-SIRT1-Autophagy Pathway.

Tryptophan has drawn wide attention due to its involvement in improving intestinal immune defense directly and indirectly by regulating metabolic pathways. The study aims to elucidate the potential modulating roles of tryptophan to protect against intestinal inflammation and elucidate the underlying molecular mechanisms. The protective effects of tryptophan against intestinal inflammation are examined in the lipopolysaccharide (LPS)-induced inflammatory model. We first found that tryptophan markedly (p < 0.01) inhibited proinflammatory cytokines production and nuclear factor κB (NF-κB) pathway activation upon LPS challenge. Next, we demonstrated that tryptophan (p < 0.05) attenuated LPS-caused intestinal mucosal barrier damage by increasing the number of goblet cells, mucins, and antimicrobial peptides (AMPs) in the ileum of mice. In addition, tryptophan (p < 0.05) inhibited LPS-induced autophagic flux through the AMP-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) pathway in the intestinal systems to maintain autophagy homeostasis. Meanwhile, tryptophan also reshaped the gut microbiota composition in LPS-challenge mice by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria such as Acetivibrio (0.053 ± 0.017 to 0.21 ± 0.0041%). Notably, dietary tryptophan resulted in the activation of metabolic pathways during the inflammatory response. Furthermore, exogenous treatment of tryptophan metabolites kynurenine (Kyn) and 5-HT in porcine intestinal epithelial cells (IPEC-J2 cells) reproduced similar protective effects as tryptophan to attenuate LPS-induced intestinal inflammation through regulating the AMPK-SIRT1-autophagy. Taken together, the present study indicates that tryptophan exhibits intestinal protective and immunoregulatory effects resulting from the activation of metabolic pathways, maintenance of gut mucosal barrier integrity, microbiota composition, and AMPK-SIRT1-autophagy level.

Biosynthesis of gold nanoparticles, characterization and their loading with zonisamide as a novel drug delivery system for the treatment of acute spinal cord injury.

In the present work, a facile biosynthetic approach for the synthesis of AuNPs using bark extract of Juglans regia (J. regia) is reported. Ultra-violet visible (UV-vis) absorption spectroscopic studies exhibited and narrow SPR absorption band at 540 nm, represented the isotropy in particle size. The transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis, confirmed the fabrication of spherical and crystalline nanoparticles of average size of about 14 nm. Also, typical characteristic selected area electron diffraction (SAED) pattern showed the crystalline nature of AuNPs. The prepared AuNPs were loaded with zonisamide which can be used for future spinal cord injury repair applications. The fourier transform infrared spectroscopy (FTIR) analysis represented the zonisamide loading onto AuNPs. The biological preparation of AuNPs using the bark extract of J. regia is prominent approach because of its eco friendly nature without using any toxic chemicals. The controlled-release of zonisamide-AuNPs was about 43.0 ±â€¯2.2 nm with high stability and solubility under room temperature conditions. Further, the cytotoxicity results showed the comparatively higher toxicity of zonisamide-AuNPs towards CTX TNA2 cells than free zonisamide. Hence, zonisamide-AuNPs may act as very good clinical drug for future therapeutic treatment of spinal cord injury.

The correlation between the high-intensity zone on a T2-weighted MRI and positive outcomes of discography: a meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the correlation between the high-intensity zone (HIZ) of a lumbar MRI and discography. METHODS: We conducted an electronic search of the PubMed, MEDLINE, Embase, and ScienceDirect databases from their respective inceptions to October 2016 using the following search terms: "low back pain," "discogenic low back pain," "HIZ or high-intensity zone," and "discography". Relevant journals and conference proceedings were manually searched. Two reviewers independently assessed the quality of the studies, extracted data from the included studies, and analyzed the data. RESULTS: Eleven studies were included. The results of the meta-analysis indicated that outstanding relativity and statistically significant correlations were observed between the HIZ and abnormal disc morphology (OR = 47.79; 95% CI: 17.07 to 133.77; P < 0.00001), HIZ and pain reproduction (OR = 8.65, 95% CI: 6.01 to 15.23, P < 0.00001), and HIZ and abnormal morphology pain reproduction (OR = 11.74, 95% CI: 1.99 to 69.36, P = 0.007). CONCLUSIONS: The presence of an HIZ on a lumbar MRI T2-weighted image indicates abnormal disc morphology. There is a strong relationship between the HIZ and pain reproduction. The HIZ can be an effective index for prediction of discogenic low back pain.

[Surgical treatment of lumbosacral tuberculosis by anterior debridement,bone graft,and posterior pedicle screw-rod internal fixation].

OBJECTIVE: To investigate the effectiveness of anterior debridement,bone graft, and posterior pedicle screw-rod internal fixation in the treatment of lumbosacral tuberculosis. METHODS: From January 2005 to June 2012,18 patients with lumbosacral tuberculosis undergoing the surgical treatment by anterior debridement, bone graft, and posterior pedicle screw-rod internal fixation were reviewed retrospectively. There were 12 males and 6 females with an average age of 44 years old ranging from 35 to 67. Among them, 2 cases were simple low back pain,3 cases were low back pain combined with radiating pain of lower extremity and 13 cases were muscle strength hypesthesia. According to Fankle grading,the nerve function was grade C in 3 cases,grade D in 10 cases,grade E in 5 cases. Of these cases,L4.5 was involved in 8 cases,L5 in 4 cases and L5S1 in 6 cases. The lumbosacral angle was 150 to 270 and the erythrocyte sedimentation rate (ESR) was 45 to 93 mm/h before treatment. The clinical indexes including the lumbosacral incidence, Frankel grade and ESR were reviewed at follow-up. RESULTS: All 18 cases were followed up for 14 to 22 months. The mean operation time was 180 min. The amount of bleeding was 400 to 800 ml. Except 1 case with iliac vein injuried and 4 cases with abdominal distension,no spinal injuries and severe relative complication occurred, and neurologic function improved in various degrees. Pain in lumbosacral area and radicular pain in lower extremities disappeared. The X-ray and CT films demonstrated that bony fusion was obtained in all patients during 9 to 13 months postoperatively. The lumbosacral angle and ESR were improved significantly. CONCLUSION: Anterior debridement, bone graft, and posterior pedicle screw-rod internal fixation is an effective method in dealing with lumbosacral spine tuberculosis.

[Case-control study on therapeutic effects between posterior corpectomy, decompression and reconstruction and combined anterior-posterior surgery for the treatment of severe thoracolumbar fractures with incomplete paraplegia].

OBJECTIVE: To compare the clinical outcome between posterior corpectomy, decompression and reconstruction and combined anterior-posterior surgery in the treatment of severe thoracolumbar three column fractures with incomplete paraplegia, and to provide a basis for procedure selection. METHODS: Clinical and radiographic results of posterior corpectomy, decompression and reconstruction (group A) and combined anterior-posterior surgery (group B) in the treatment of severe thoracolumbar three column fractures with incomplete paraplegia were analyzed retrospectively from January 2008 to December 2012. In group A, there were 18 patients (10 males and 8 females). The fractures were located on T11 in 1 case, T12 in 5 cases, L1 in 6 cases and L2 in 6 cases. In group B, there were 15 patients (9 males and 6 females). The fractures were located on T1 in 1 case, T12 in 5 cases, L1 in 5 cases and L2 in 4 cases. Neurological status was judged by Frankel grades. The X-ray and CT were used for evaluation of the restoration of anterior height of the fractured vertebral body, the correction of Cobbs angle, the decompression scope of spinal canal and the fusion. Complications related to operation were also considered. Results: The followup periods ranged from 12 to 18 months (averaged 16 months). The mean operation time, perioperative bleeding, postoperative drainage were (200 ± 43) min, (1100 ± 344) ml, and (400 ± 112) ml respectively in group A; and (290 ± 68) min, (1 500 ± 489) ml, (900 ± 269) ml respectively in group B. There was statistically significant difference between groups A and B (P < 0.05). There were significant improvements in anterior height of fractured vertebral body and Cobbs angle after operation. But there was no significant difference between groups A and B (P > 0.05). In Frankel grades, all patients had one grade or more improvement postoperatively. There was no significant difference between two groups (P > 0.05). CONCLUSION: Treatment of thoracolumbar vertebra burst fractures with subtotal vertebrectomy, decompression and reconstruction of anterior column through posterior approach has a similar clinical result compared to the operation through combined anterior and posterior approach, but the posterior surgery decreased surgical trauma. It is an effective and safe surgical method.