2D nanomaterials-based delivery systems and their potentials in anticancer synergistic photo-immunotherapy.

As the field of cancer therapeutics evolves, integrating two-dimensional (2D) nanomaterials with photo-immunotherapy has emerged as a promising approach with significant potential to augment cancer treatment efficacy. These 2D nanomaterials include graphene-based 2D nanomaterials, 2D MXenes, 2D layered double hydroxides, black phosphorus nanosheets, 2D metal-organic frameworks, and 2D transition metal dichalcogenides. They exhibit high load capacities, multiple functionalization pathways, optimal biocompatibility, and physiological stability. Predominantly, they function as anti-tumor delivery systems, amalgamating diverse therapeutic modalities, most notably phototherapy and immunotherapy, and the former is a recognized non-invasive treatment modality, and the latter represents the most promising anti-cancer strategy presently accessible. Thus, integrating phototherapy and immunotherapy founded on 2D nanomaterials unveils a novel paradigm in the war against cancer. This review delineates the latest developments in 2D nanomaterials as delivery systems for synergistic photo-immunotherapy in cancer treatment. We elaborate on the burgeoning realm of photo-immunotherapy, exploring the interplay between phototherapy and enhanced immune cells, immune response modulation, or immunosuppressive tumor microenvironments. Notably, the strategies to augment photo-immunotherapy have also been discussed. Finally, we discuss the challenges and future perspectives of these 2D nanomaterials in photo-immunotherapy.

Immunomodulatory nanomedicine for osteoporosis: Current practices and emerging prospects.

Osteoporosis results from the disruption of the balance between bone resorption and bone formation. However, classical anti-osteoporosis drugs exhibit several limitations in clinical applications, such as multiple adverse reactions and poor therapeutic effects. Therefore, there is an urgent need for alternative treatment strategies. With the evolution of immunomodulatory nanomedicine, a variety of nanomaterials have been designed for anti-osteoporosis treatment, offering prospects of minimal adverse reactions, enhanced bone induction, and high osteogenic activity. This review initially provides a brief overview of the fundamental principles of bone reconstruction, current osteogenic clinical methods in osteoporosis treatment, and the significance of osteogenic-angiogenic coupling, laying the groundwork for understanding the pathophysiology and therapeutics of osteoporosis. Subsequently, the article emphasizes the relationship between bone immunity and osteogenesis-angiogenesis coupling and provides a detailed analysis of the application of immunomodulatory nanomedicines in the treatment of osteoporosis, including various types of nanomaterials and their integration with carrier biomaterials. Importantly, we discuss the potential of some emerging strategies in immunomodulatory nanomedicine for osteoporosis treatment. This review introduces the innovative applications of immunomodulatory nanomedicine in the treatment of osteoporosis, aiming to serve as a reference for the application of immunomodulatory nanomedicine strategies in osteoporosis treatment. STATEMENT OF SIGNIFICANCE: Osteoporosis, as one of the most prevalent skeletal disorders, poses a significant threat to public health. To date, conventional anti-osteoporosis strategies have been limited in efficacy and plagued with numerous side effects. Fortunately, with the advancement of research in osteoimmunology and nanomedicine, strategies integrating these two fields show great promise in combating osteoporosis. Nanomedicine with immunomodulatory properties exhibits enhanced efficiency, prolonged effectiveness, and increased safety. However, as of now, there exists no comprehensive review amalgamating immunomodulation with nanomedicine to delineate the progress of immunomodulatory nanomedicine in osteoporosis treatment, as well as the future direction of this strategy.

Urinary exosomal miRNA-451a can be used as a potential noninvasive biomarker for diagnosis, reflecting tubulointerstitial damage and therapeutic response in IgA nephropathy.

To investigate the potential clinical value of urinary exosomal (uE) miR-451a as a biomarker for IgAN, urinary exosomes were isolated from 40 patients with IgAN, 30 patients with primary renal diseases without IgA as disease controls (non-IgAN group) and 21 healthy controls (HCs). The expression of miR-451a within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). uE miR-451a was significantly upregulated in patients with IgAN compared to non-IgAN and HCs. The uE miR-451a level was positively correlated with the change in eGFR and negatively correlated with serum creatinine, urinary macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). A dual-luciferase reporter assay confirmed that MIF was a direct target of miR-451a. Receiver operating characteristic (ROC) curve analysis revealed that the expression of uE miR-451a showed potential diagnostic value for IgAN. Additionally, the uE miR-451a level could distinguish patients with IgAN with mild tubular atrophy/interstitial fibrosis from those with severe tubular atrophy/interstitial fibrosis. After a mean follow-up of 14.2 months, the levels of eGFR loss (ml/min/1.73 m2/year) were negatively correlated with baseline miR-451a. The levels of baseline miR-451a in the complete remission group were significantly higher than those in the non-complete remission group. uE miR-451a expression was significantly elevated in patients with IgA nephropathy and may serve as a potential biomarker for the diagnosis of IgAN and evaluation of tubulointerstitial damage, while the baseline levels of uE miR-451a may be predictors of therapeutic efficacy and disease progression.

Metal-Organic Framework-Based Nanomaterials for Regulation of the Osteogenic Microenvironment.

As the global population ages, bone diseases have become increasingly prevalent in clinical settings. These conditions often involve detrimental factors such as infection, inflammation, and oxidative stress that disrupt bone homeostasis. Addressing these disorders requires exogenous strategies to regulate the osteogenic microenvironment (OME). The exogenous regulation of OME can be divided into four processes: induction, modulation, protection, and support, each serving a specific purpose. To this end, metal-organic frameworks (MOFs) are an emerging focus in nanomedicine, which show tremendous potential due to their superior delivery capability. MOFs play numerous roles in OME regulation such as metal ion donors, drug carriers, nanozymes, and photosensitizers, which have been extensively explored in recent studies. This review presents a comprehensive introduction to the exogenous regulation of OME by MOF-based nanomaterials. By discussing various functional MOF composites, this work aims to inspire and guide the creation of sophisticated and efficient nanomaterials for bone disease management.

Metal ions: the unfading stars of bone regeneration-from bone metabolism regulation to biomaterial applications.

In recent years, bone regeneration has emerged as a remarkable field that offers promising guidance for treating bone-related diseases, such as bone defects, bone infections, and osteosarcoma. Among various bone regeneration approaches, the metal ion-based strategy has surfaced as a prospective candidate approach owing to the extensive regulatory role of metal ions in bone metabolism and the diversity of corresponding delivery strategies. Various metal ions can promote bone regeneration through three primary strategies: balancing the effects of osteoblasts and osteoclasts, regulating the immune microenvironment, and promoting bone angiogenesis. In the meantime, the complex molecular mechanisms behind these strategies are being consistently explored. Moreover, the accelerated development of biomaterials broadens the prospect of metal ions applied to bone regeneration. This review highlights the potential of metal ions for bone regeneration and their underlying mechanisms. We propose that future investigations focus on refining the clinical utilization of metal ions using both mechanistic inquiry and materials engineering to bolster the clinical effectiveness of metal ion-based approaches for bone regeneration.

Multifunctional modifications of polyetheretherketone implants for bone repair: A comprehensive review.

Polyetheretherketone (PEEK) has emerged as a highly promising orthopedic implantation material due to its elastic modulus which is comparable to that of natural bone. This polymer exhibits impressive properties for bone implantation such as corrosion resistance, fatigue resistance, self-lubrication and chemical stability. Significantly, compared to metal-based implants, PEEK implants have mechanical properties that are closer to natural bone, which can mitigate the "stress shielding" effect in bone implantation. Nevertheless, PEEK is incapable of inducing osteogenesis due to its bio-inert molecular structure, thereby hindering the osseointegration process. To optimize the clinical application of PEEK, researchers have been working on promoting its bioactivity and endowing this polymer with beneficial properties, such as antibacterial, anti-inflammatory, anti-tumor, and angiogenesis-promoting capabilities. Considering the significant growth of research on PEEK implants over the past 5 years, this review aims to present a timely update on PEEK's modification methods. By highlighting the latest advancements in PEEK modification, we hope to provide guidance and inspiration for researchers in developing the next generation bone implants and optimizing their clinical applications.

Knee and hip arthroplasty joint surgical site wound infection in end-stage renal disease subjects who underwent dialysis or a kidney transplant: A meta-analysis.

A meta-analysis study to assess the knee and hip arthroplasty joint surgical site wound infection (SSWI) in end-stage renal disease (ESRD) subjects who underwent dialysis or a kidney transplant (KT). A comprehensive literature examination till February 2023 was implemented and 1046 linked studies were appraised. The picked studies contained 5 471 898 subjects with total joint arthroplasty (TJA) at the baseline, 13 049 of them were haemodialysis or renal transplant, and 5 458 849 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of knee and hip arthroplasty SSWI in ESRD subjects who underwent dialysis or a KT by the dichotomous and continuous styles and a fixed or random model. Haemodialysis or renal transplant had a significantly higher postoperative SSWI (OR, 2.13; 95% CI, 1.73-2.62, P < .001) compared with control in TJA subjects. However, no significant difference was observed between haemodialysis and renal transplant in postoperative SSWI (OR, 0.93; 95% CI, 0.16-5.54, P = .94) and between haemodialysis or renal transplant and control in prosthetic joint infection (OR, 1.07; 95% CI, 0.25-4.55, P = .93) in TJA subjects. Haemodialysis had a significantly higher prosthetic joint infection (OR, 1.92; 95% CI, 1.21-3.03, P = .005) compared with renal transplant in TJA subjects. Haemodialysis or renal transplant had a significantly higher postoperative SSWI in TJA subjects. Also, haemodialysis had a significantly higher prosthetic joint infection compared with renal transplant in TJA subjects. Although precautions should be taken when commerce with the consequences because a low number of selected studies was picked for certain comparisons in this meta-analysis.

Preliminary study on the efficacy of rituximab in the treatment of idiopathic membranous nephropathy: A single-centre experience.

Objective: To investigate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy (IMN). Methods: A total of 77 patients with IMN diagnosed in both our hospital and other hospitals were included in this study; the patients were divided into two groups: a treatment-naïve group (n = 19) and a refractory/relapsed group (n = 58). The clinical data of the patients, including urine examination, blood test, safety evaluation and efficacy evaluation results, were analysed retrospectively. The changes in clinical biochemical indexes and adverse reactions were compared between the two groups before and after treatment, and the clinical efficacy of rituximab (RTX) in the treatment of primary IMN and refractory recurrent membranous nephropathy was evaluated. Results: Of the 77 patients included in this study, the average age was 48 years, and there was a male-to-female ratio of 61:16. There were 19 cases in the initial treatment group and 58 cases in the refractory/relapse group. The 24-hour urine protein quantification, cholesterol, B cell count and M-type phospholipase A2 receptor (PLA2R) results in the 77 patients with IMN after treatment were all lower than those before treatment, and the differences were statistically significant (P < 0.05). Serum albumin was higher than before treatment, and the difference was statistically significant (P < 0.05). The total remission rate in the initial and refractory/relapsed treatment groups was 84.21% and 82.76%, respectively. There was no statistical difference in the total remission rate between the two groups (P > 0.05). During treatment, nine patients (11.69%) experienced infusion-related adverse reactions, which were relieved rapidly after symptomatic treatment. The anti-PLA2R antibody titre of the refractory/relapsed group was significantly negatively correlated with serum creatinine (r = -0.187, P = 0.045) and significantly correlated with 24-hour urine protein (r = -0.490, P < 0.001). There was a positive correlation and a significant negative correlation with serum albumin (r = -0.558, P < 0.001). Conclusions: Regardless of whether RTX is used as an initial therapy or refractory/relapsed membranous nephropathy, most patients with IMN have complete or partial remission after RTX treatment, with mild adverse reactions.

Oral and intravenous iron treatment alter the gut microbiome differentially in dialysis patients.

OBJECTIVE: Chronic kidney disease (CKD) is often complicated by anemia, which seriously affects the quality-of-life and prognosis of patients. These patients usually need iron replacement therapy. Oral iron affects the composition and abundance of intestinal flora by increasing intestinal iron concentration. METHODS: We undertook an interventional study to investigate the effects of oral versus intravenous iron therapy on the gut microbiota. Oral ferrous succinate tablets (n = 14) or intravenous iron sucrose (n = 14) was administered to anemic maintenance hemodialysis (MHD) patients for 2 months. RESULTS: Oral and intravenous iron treatments had different effects on gut microbial composition and diversity. After oral iron treatment, the α-diversity was decreased, while at the phylum level, the abundance of Firmicutes was reduced and the abundance of Bacteroides was increased. At the genus level, the abundance of Blautia and Coprococcus was decreased, and the abundance of Bacteroidetes was increased. Oral iron therapy was associated with a higher abundance of Lactobacillus compared with that measured in intravenous iron-treated patients. According to metagenome function prediction analysis, oral iron increased the metabolic processes of phenylalanine, valine, leucine, and isoleucine. These changes may increase uremic toxin levels, thereby increasing the progression of renal disease. CONCLUSION: Iron therapy affects the diversity and composition of gut flora in MHD patients. Oral iron affects the number of bacteria and increases amino acid metabolism compared with intravenous iron. These results indicate that intravenous iron may be more appropriate for MHD patients.

Glomerular solidification is associated with nephritis-related clinical parameters in IgA nephropathy.

Background: Two types of global glomerulosclerosis, glomerular obsolescence and solidification, have been identified. A clinicopathological correlation between these glomerular changes and hypertensive nephrosclerosis has been reported; however, clinicopathological correlations with other kidney diseases are unknown. The aim of this study was to evaluate the correlation between the two glomerulosclerosis types and the clinical IgA nephropathy presentation. Methods: A single center, cross-sectional study of patients with IgA nephropathy was performed. Correlations between glomerulosclerosis and body mass index, mean blood pressure, creatinine-based estimated glomerular filtration rate (eGFR), total cholesterol, urinary protein corrected by urinary creatinine, and anti-hypertensive agent use were investigated using univariate and multivariate analyses. Results: Overall, 116 patients were enrolled (male/female, 59/57; mean age, 40.5 ± 15.0 years). Separate analyses were performed for solidification and obsolescence glomerulosclerosis. Univariate analysis demonstrated a significant correlation between the percentage of solidification glomerulosclerosis and patient age, mean blood pressure, eGFR, and use of antihypertensive drugs. Multivariate analysis showed that only eGFR and use of antihypertensive drugs maintained their independent predictive value. The amount of urinary protein emerged as a significant factor based on the multivariate analysis. However, although the univariate analysis demonstrated a statistically significant correlation between the percentage of obsolescence and eGFR for obsolescence glomerulosclerosis, a multivariate analysis indicated that none of the factors maintained their independent predictive value. Conclusions: The incidence of solidification was better correlated with some nephritis-related clinical parameters compared with the incidence of obsolescence. The emergence of solidification may influence the clinical activities that are associated with IgA nephropathy.

Trifluoperazine induces apoptosis through the upregulation of Bax/Bcl­2 and downregulated phosphorylation of AKT in mesangial cells and improves renal function in lupus nephritis mice.

The inhibition of mesangial cell (MC) proliferation has become an important therapy in preventing glomerular proliferation diseases. Trifluoperazine (TFP) has been reported to inhibit the proliferation of several types of cancer cell, however, the effects of TFP in renal proliferation diseases remain to be fully elucidated. The present study examined the effects of TFP on the proliferation of MCs and quantified cell apoptosis progression in vivo and in vitro. The effects of various TFP concentrations and treatment durations on cell proliferation and cell apoptosis in vitro were analyzed using flow cytometry in conjunction with a Cell Counting kit­8 assay. Cell proliferation in vivo was determined using hematoxylin and eosin staining and immunohistochemistry of Ki67. The expression of the two cell apoptosis­related proteins, B­cell lymphoma-2 (Bcl­2) and Bcl­2­associated X protein (Bax), were estimated using western blot analysis and immunohistochemistry in vivo and in vitro. TFP­induced phosphatidylinositol 3­kinase (PI3K)/protein kinase B (AKT) signaling pathways were also estimated using western blot analysis. These results suggested that TFP inhibited MC proliferation in a dose­ and time­dependent manner. It was found that TFP inhibited the abnormal proliferation of MCs, which was stimulated by 20% fetal bovine serum in vitro and in lupus MRL/lpr mice. TFP promoted cell apoptosis, downregulated the expression of Bcl­2 and upregulated the expression of Bax in a dose­dependent manner at mRNA and protein levels. In addition, TFP inhibited phosphorylated AKT, potentially leading to the suppressed activation of PI3K/AKT signaling pathways. TFP treatment significantly decreased the levels of blood urea nitrogen and serum creatinine, but had no significant effects on the body weight and liver function of the lupus mice. These results validated and reinforced the potential of TFP in the treatment of mesangial proliferative diseases.