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Objective: The release of adipose tissue-derived miRNAs is increased under conditions of obesity, but the exact molecular mechanisms involved have not been elucidated. This study investigated whether obesity-induced increases in palmitic acid (PA) content could activate the NF-κB/endoplasmic reticulum stress (ER stress) pathway and promote the expression and release of exosomal miRNAs in adipocytes. Methods: Abdominal adipose tissue and serum samples were collected from normal weight individuals and people with obesity to clarify the correlation of serum PA content with NF-κB/ER stress and the release of exosomal miRNAs. NF-κB and ER stress were blocked in obese mice and in vitro cultured adipocytes to demonstrate the molecular mechanisms by which PA promotes the release of exosomal miRNAs.The morphology, particle size and distribution of the exosomes were observed via transmission electron microscopy and NTA. Results: Accompanied by increased serum PA levels, the NF-κB/ER stress pathway was activated in the adipose tissue of people with obesity and in high-fat diet (HFD)-induced obese mice; moreover, the levels of miRNAs in both adipose tissue and serum were increased. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reduced the levels of miRNAs in abdominal adipose tissue and serum, decreased blood glucose levels, and improved glucose tolerance and insulin sensitivity in obese mice. In 3T3-L1 adipocytes, high concentrations of PA activated the NF-κB/ER stress pathway and increased the expression and release of miRNAs in exosomes. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reversed the increased release exosomal miRNAs cause by PA. Conclusions: Obesity-induced increases in PA content increase the expression and release of miRNAs in adipocyte exosomes by activating the NF-κB/ER stress pathway. [ABSTRACT FROM AUTHOR]

A 64-year-old man presented with diffuse patchy alopecia for one month. He had a 17-year history of moderate to severe plaque psoriasis. Significant resolution of psoriasis lesions occurred during preventive anti-tuberculosis therapy using isoniazid and rifampicin. However, diffuse patchy alopecia areata developed. After withdrawal of anti-tuberculosis drugs and administration of glucocorticoids, alopecia areata was in remission gradually. However, psoriatic lesions returned. Anti-tuberculosis drugs may exert anti-inflammatory and immunomodulatory effects through multiple key factors. [ABSTRACT FROM AUTHOR]

Ferroptosis is a lipid peroxidation-driven cell death route and has attracted enormous interest for cancer therapy. Distinct from other forms of regulated cell death, its process is involved with multiple metabolic pathways including lipids, bioenergetics, iron, and so on, which influence cancer cell ferroptosis sensitivity and communication with the immune cells in the tumor microenvironment. Development of novel technologies for harnessing the ferroptosis-associated metabolic regulatory network would profoundly improve our understanding of the immune responses and enhance the efficacy of ferroptosis-dependent immunotherapy. Interestingly, the recent advances in bio-derived material-based therapeutic platforms offer novel opportunities to therapeutically modulate tumor metabolism through the in situ delivery of molecular or material cues, which not only allows the tumor-specific elicitation of ferroptosis but also holds promise to maximize their immunostimulatory impact. In this review, we will first dissect the crosstalk between tumor metabolism and ferroptosis and its impact on the immune regulation in the tumor microenvironment, followed by the comprehensive analysis on the recent progress in biomaterial-based metabolic regulatory strategies for evoking ferroptosis-mediated antitumor immunity. A perspective section is also provided to discuss the challenges in metabolism-regulating biomaterials for ferroptosis-immunotherapy. We envision that this review may provide new insights for improving tumor immunotherapeutic efficacy in the clinic., (© 2024 Wiley Periodicals LLC.)

Titanium and its alloys are the most commonly used biometals for developing orthopedic implants to treat various forms of bone fractures and defects, but their clinical performance is still challenged by the unfavorable mechanical and biological interactions at the implant-tissue interface, which substantially impede bone healing at the defects and reduce the quality of regenerated bones. Moreover, the impaired osteogenesis capacity of patients under certain pathological conditions such as diabetes and osteoporosis may further impair the osseointegration of Ti-based implants and increase the risk of treatment failure. To address these issues, various modification strategies have been developed to regulate the implant-bone interactions for improving bone growth and remodeling in situ . In this review, we provide a comprehensive analysis on the state-of-the-art synthetic nanointerfacial bioengineering strategies for designing Ti-based biofunctional orthopedic implants, with special emphasis on the contributions to (1) promotion of new bone formation and binding at the implant-bone interface, (2) bacterial elimination for preventing peri-implant infection and (3) overcoming osseointegration resistance induced by degenerative bone diseases. Furthermore, a perspective is included to discuss the challenges and potential opportunities for the interfacial engineering of Ti implants in a translational perspective. Overall, it is envisioned that the insights in this review may guide future research in the area of biometallic orthopedic implants for improving bone repair with enhanced efficacy and safety.

The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics., 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.)

Reconstruction and healing of large craniofacial bone defects are major clinical challenges due to high risk of chronic inflammation and reduced cell mineralization levels. Herein, a core-shell nanofiber-based implant with significant pro-osteogenesis capability for treating skull defects is reported, which is hierarchically integrated with curcumin-loaded calcium carbonate nanoparticles (CaCO 3 @Cur NPs) in the outer layers and black phosphorus nanosheets (BPNSs) in the core compartments. The radical alignment of the integrated nanocomponents allows the sequential in situ release of the therapeutic agents in a controlled manner after implantation. Curcumin can repolarize M1 macrophages into M2 phenotypes for anti-inflammation purposes. Meanwhile, the released calcium and phosphate ions can promote the biomineralization of hydroxyapatite at the defect site and facilitate bone regeneration. Evaluations on cranial defect-bearing rat models demonstrated that the electrospun fibers in the present study substantially promoted restoration of the damaged skulls and inhibited inflammation in the wound bed. This strategy provides a new idea for the treatment of skull defects in the clinic., (© 2024 Wiley‐VCH GmbH.)

Melanoma is one of the most severe skin cancer indications with rapid progression and a high risk of metastasis. However, despite the accumulated advances in melanoma treatment including adjuvant radiation, chemotherapy, and immunotherapy, the overall melanoma treatment efficacy in the clinics is still not satisfactory. Interestingly, bacterial therapeutics have demonstrated unique properties for tumor-related therapeutic applications, such as tumor-targeted motility, tailorable cytotoxicity, and immunomodulatory capacity of the tumor microenvironment, which have emerged as a promising platform for melanoma therapy. Indeed, the recent advances in genetic engineering and nanotechnologies have boosted the application potential of bacterium-based therapeutics for treating melanoma by further enhancing their tumor-homing, cell-killing, drug delivery, and immunostimulatory capacities. This review provides a comprehensive summary of the state-of-the-art bacterium-based anti-melanoma modalities, which are categorized according to their unique functional merits, including tumor-specific cytotoxins, tumor-targeted drug delivery platforms, and immune-stimulatory agents. Furthermore, a perspective is provided discussing the potential challenges and breakthroughs in this area. The insights in this review may facilitate the development of more advanced bacterium-based therapeutic modalities for improved melanoma treatment efficacy., (© 2024 Wiley‐VCH GmbH.)

Objective: To establish and evaluate a microbial sensitivity test method for Neisseria gonorrhoeae based on resazurin coloration., Methods: Based on the broth microdilution method, resazurin was added as a live bacteria indicator. WHO G, a WHO gonococcal reference strain, was used to optimize the incubation time for resazurin-stained bacteria and the color change was visually observed to obtain the results. Agar dilution method (the gold standard) and resazurin-based microdilution assay were used to determine the minimum inhibitory concentration (MIC) of azithromycin, ceftriaxone, and spectinomycin for 3 reference strains and 32 isolates of Neisseria gonorrhoeae . The results were analyzed based on essential agreement (EA), which reflected the consistency of the MIC values, category agreement (CA), which reflected the consistency in the determination of drug resistance, intermediary, and sensitivity, very major error (VME), which reflected false sensitivity, and major error (ME), which reflected pseudo drug resistance, to evaluate the accuracy of resazurin-based microdilution assay as a microbial sensitivity test of of Neisseria gonorrhoeae . CA and EA rates≥90% and VME and ME rates≤3% were found to be the acceptable performance rates., Results: The results obtained 6 hours after resazurin was added were consistent with those of the agar dilution method and the resazurin-based microdilution assay was established accordingly based on this parameter. The EA of resazurin-based microdilution assay for measuring the MIC results of azithromycin, ceftriaxone, and spectinomycin was 97.1%, 91.5%, and 94.3%, respectively, and the CA was 88.6%, 94.3%, and 94.3%, respectively. The VME was 0% for all three antibiotics, while the ME was 11.4%, 5.7%, and 5.7%, respectively., Conclusion: The resazurin-based microdilution assay established in this study showed good agreement with agar dilution method for measuring the MIC of antibiotics against Neisseria gonorrhoeae . Moreover, the sensitivity results of this method were highly reliable and could be easily obtained through naked eye observation. Nonetheless, the results of drug resistance should be treated with caution and the optimization of parameters should be continued., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)