The renal regenerative capacity hinges on tubular epithelial cell (TEC) plasticity, while Macrophage activation and their crosstalk with tubular cells further drive ischemia–reperfusion injury (IRI) progression, where epigenetic regulation critically directs cellular fate. Based on the established association between HDAC dysregulation—specifically HDAC1—and renal injury, we investigated the therapeutic strategies and and epigenetic regulatory mechanisms underlying mechanisms of the selective HDAC1 inhibitor FK228 in renal IRI. This study employed IRI animal models, along with in vitro culture systems of TECs and bone marrow-derived macrophages (BMDMs). A range of immunological and molecular biology techniques was used to assess TEC apoptosis and repair, as well as macrophage migration and polarization, with key molecular changes and their interactions visualized, too. Our findings demonstrate that FK228 confers renoprotection in renal IRI through HDAC1-dependent modulation of p53 activity, coordinating the regulation of apoptotic pathways (P53-Caspase-3) and proliferative responses in tubular epithelium while attenuating oxidative stress and modulating macrophage crosstalk. And beyond that, FK228 delays IRI progression and fibrosis by inhibiting the HDAC1-HIF-1α-NF-κB signaling axis, thereby suppressing morphological transformation and limiting macrophage proliferation and differentiation. Confocal microscopy revealed that FK228 redistributes phosphorylated NF-κB p65 and HIF-1α to the cytoplasm while reducing their nuclear co-localization. In conclusion, This study demonstrates that FK228 protects TECs from IRI by modulating the p53-Caspase-3/Bcl-2 pathway to inhibit apoptosis. Additionally, FK228 targets the HDAC1-HIF-1α-NF-κB axis to suppress pathological macrophage polarization, thereby delaying renal fibrosis and ameliorating both acute injury and its chronic progression. This schematic summarizes the mechanism by which FK228, an HDAC1 inhibitor, regulates renal injury and repair following IRI. IRI induces aberrant p53 acetylation in TECs, leading to activation of the Caspase-3-mediated apoptotic pathway and recruitment of macrophages, which exacerbates tissue damage. In the sustained IRI microenvironment, M1 macrophages promote M2 polarization, macrophage-myofibroblast transition (MMT), and subsequent fibrosis by releasing inflammatory cytokines via NF-κB p65 phosphorylation and nuclear translocation, along with activation of HIF-1α signaling. FK228 restores the balance of p53 acetylation through HDAC1 inhibition, thereby reducing apoptosis and mitigating macrophage-mediated injury. Concurrently, FK228 blocks NF-κB p65 phosphorylation and nuclear translocation, restores p65 acetylation levels, and diminishes its nuclear co-localization with HIF-1α, ultimately suppressing macrophage polarization and delaying fibrosis. Red arrows indicate pro-inflammatory or pro-fibrotic pathways, while green T-bars denote the inhibitory effects of FK228. • FK228 confers dual protection against IRI-induced acute kidney damage, subsequent renal fibrosis. • FK228 alleviates macrophage migration and tubular apoptosis by modulating the caspase-3 pathway via acetylation-dependent p53 regulation of the Bcl-2 family. • FK228 protects against IRI-induced renal impairment and fibrosis by reducing mononuclear cell infiltration and suppressing the expansion of M1, M2, and MMT cells. • FK228 altered NF-κB p65 modifications and diminished its cytoplasmic co-localization with HIF-1α in activated macrophages, subsequently modulating their polarization.

Osteoarthritis (OA) is a prevalent degenerative joint disease with limited diagnostic biomarkers. Triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of inflammation and bone metabolism, but its role in OA remains unclear. Plasma and synovial fluid samples were collected from patients with OA and patients with joint trauma serving as controls. Levels of TREM2 and IL-6 were measured using RT-qPCR and ELISA. Correlation analyses were conducted to assess relationships among TREM2, IL-6, and clinical parameters. The diagnostic value of TREM2 was evaluated via receiver operating characteristic (ROC) curve analysis. Additionally, the role and regulatory mechanism of TREM2 were investigated in lipopolysaccharide (LPS)-induced chondrocytes. TREM2 levels were significantly elevated in both plasma and synovial fluid of patients with OA and showed positive correlations with IL-6, Kellgren-Lawrence score and body mass index (BMI). ROC analysis revealed AUCs of 0.880 for plasma TREM2 and 0.869 for synovial fluid TREM2, with superior performance compared to IL-6 in the same cohort. Multivariate logistic regression confirmed that TREM2 remained independently associated with OA after adjusting for confounders (OR = 28.29, P = 0.006). In vitro, LPS treatment upregulated TREM2 expression in chondrocytes, which was associated with changes in cell proliferation, apoptosis, inflammatory cytokine release and oxidative stress, with preliminary evidence suggesting involvement of the NLRP3-mediated pyroptosis-associated pathway. Elevated TREM2 in plasma and synovial fluid represents a promising exploratory biomarker for OA. In vitro findings suggest that TREM2 may modulate chondrocyte functions in association with NLRP3 inflammasome-associated molecular pathways.

Acute kidney injury (AKI) is a clinical syndrome characterized by complex etiologies and usually lacks obvious clinical manifestations at the early stage. Compared with traditional imaging methods, optical imaging is broadly considered to be a promising technique for diagnosis of kidney dysfunction own to the merits of noninvasiveness, high sensitivity and fast feedback speed. Herein, we report a water-soluble fluorophore, PEG-TBSe, for in vivo imaging across diverse AKI models in the second near-infrared (NIR-II, 1000–1700 nm) window. Notably, PEG-TBSe possesses an ultrasmall size (~5.5 nm) that is suitable for renal clearance, allowing for comprehensive assessment of AKI severity in pre-renal, renal and post-renal models. In addition, the real-time imaging capacities of PEG-TBSe are sensitive to early changes in AKI, enabling the noninvasive identification of renal lesions earlier than common clinical assays. Overall, this study demonstrates the first NIR-II small molecular probe for the early diagnosis and evaluation of the severity of kidney dysfunction in different AKI models.

Noninvasive detection of BK virus, for early detection of BK polyomavirus-associated nephropathy post-renal transplantation, is currently an active subject of investigation. In this study, we developed and validated a novel risk score diagnostic assay (PymiR Score) based on measurements of three urine miRNAs, including BKV-related miRNA (bkv-miR-B1-5p), polyomavirus-related miRNA (bkv-miR-B1-3p) and renal tubular injury-related miRNA (miR-21-5p), by quantitative polymerase chain reaction. The limit of detection of the three miRNAs was 2 × 103 copies/mL, while the intra- and inter-assay coefficients of variation were in the ranges of 2.13 %-3.59 % and 2.30 %-3.35 %, respectively. In the training set, we identified that at a PymiR Score of 71.78, the maximum sensitivity and specificity for the detection of BKVAN were 76.9 % and 100 % respectively, with the receiver-operator characteristic (ROC) analysis showing an area under the curve of 0.8681. In the validation set, we observed a significant difference in the PymiR Score between BKV infection and biopsy-proven BKVAN (P ＜ 0.05), with the ROC analysis showing a sensitivity of 72.73 %, specificity of 100 %, and an AUC of 0.8571. Compared with the area under the ROC curve of plasma BK virus DNA load (AUC = 0.7266), the PymiR Score exhibited higher discrimination capacity (P＜0.05) between BKV infection and biopsy-proven BKVAN. Overall, this non-invasive approach offers a robust and convenient alternative for the diagnosis of BK polyomavirus-associated nephropathy.

Bladder cancer is a common urological malignancy characterized by high morbidity, high recurrence rate and high mortality, imposing heavy burdens on patients mentally and financially. The research pioneers a diagnostic and therapeutic approach that integrates a second near-infrared (NIR-II) multimodal phototheranostic platform with optical fiber-mediated interventional phototherapy strategy, to implement a comprehensive diagnosis and "inside-out" treatment of bladder cancer. The proposed molecule, namely BTO-TTQ, is elaborately designed through electron donor/π-bridge engineering and demonstrates satisfying NIR-II emission with aggregation-induced emission features, high photothermal conversion efficiency, and prominent generation of type I reactive oxygen species. Quantum chemical calculations and molecular dynamics simulations are employed to deeply elucidate the energy dissipation pathways of the excited state and the impact of intramolecular motion on their photophysical properties. Furthermore, under the guidance of NIR-II fluorescent-photoacoustic-photothermal trimodal imaging, hyaluronic acid-modified BTO-TTQ nanoparticles exhibit exceptional performance in optical fiber-mediated interventional phototherapy for air-pouch bladder cancer models. This study thus brings a new insight into the development of superior versatile phototheranostics for clinical theranostics of bladder cancer.

BackgroundLaparoscopic living donor nephrectomy (LLDN) is the preferred technique for living donor kidney transplantation, but multiple renal arteries pose challenges due to increased surgical complexity. While cases with up to seven renal arteries have been reported, the occurrence of kidneys with more than three renal arteries is extremely rare. This report presents a successful retroperitoneoscopic nephrectomy in a living donor with five renal arteries, a case not previously detailed in the literature.Case reportA 65-year-old female donor with five left renal arteries underwent retroperitoneoscopic LLDN. The kidney was reconstructed ex vivo using the recipient's internal iliac artery trunk and its branches. Vascular reconstruction was achieved by anastomosing the donor's renal arteries to the recipient's iliac artery branches, forming a single arterial ostium, which was then anastomosed to the recipient's external iliac artery. The recipient, a 33-year-old male, also underwent concurrent repair of a left inguinal hernia. Postoperative outcomes were excellent, with immediate graft function, no dialysis requirement, and stable renal function at 60 days post-transplant.ConclusionThis case demonstrates that retroperitoneoscopic LLDN for kidneys with five renal arteries is technically feasible and safe. It highlights the utility of the recipient's internal iliac artery for ex vivo reconstruction, expanding the potential for successful transplantation in complex anatomical scenarios.

Activating the cGAS-STING pathway presents a promising strategy to enhance the innate immunity and combat the immunosuppressive tumor microenvironment. One key mechanism for triggering this pathway involves the release of damaged DNA fragments caused by nuclear DNA damage. However, conventional cGAS-STING agonists often suffer from limited nucleus-targeting efficiency and potential biotoxicity. In this study, we develop a novel nucleus-targeting theranostic nanoplatform designed to synergistically activate the cGAS-STING pathway through the combination of photodynamic therapy (PDT) and cisplatin chemotherapy for orthotopic bladder cancer treatment. The nanoplatform integrates a new high-performance type-I photosensitizer with near-infrared-II emission, a TATSA peptide for enhanced nuclear targeting, and a biosafe platinum (IV) cisplatin prodrug. Upon NIR laser irradiation, the nanoagent delivers synergistic nucleus-targeted PDT and chemotherapy, causing substantial DNA damage and the release of double-stranded DNA, which subsequently activates the cGAS-STING pathway and triggers potent immunomodulation. This activation promotes dendritic cells maturation, enhances cytotoxic T infiltration, and facilitates the formation of memory T cells, leading to immune microenvironment remodeling, and long-lasting immune memory, thus effectively inhibiting orthotopic bladder tumors and reducing the risk of metastasis. These findings highlight the substantial potential of this strategy to overcome the limitations of current immunotherapies by leveraging nucleus-targeted PDT to activate the cGAS-STING pathway for cancer treatment.

Prostate-specific membrane antigen (PSMA) is a protein primarily overexpressed on the surface of prostate cancer (PCa) cells, making it a key target for PSMA-based theranostics, which combine diagnostic imaging and therapy. PSMA-based molecular probes, conjugated tracers and isotopes, and multifunctional imaging technologies have significantly advanced the landscape of high-risk PCa management, particularly during initial diagnosis and treatment planning. This tool is especially crucial as the ratio of mortality to incidence of PCa in Asian populations is higher, and the overall prognosis is significantly worse compared to Western countries. Furthermore, prostate-specific antigen (PSA) screening using multiparametric magnetic resonance imaging (MRI) and pathological examination shows that only a small percentage of men (below 30%) with PSA levels between 4–10 ng/ml in China, considered low risk, actually test positive for PCa when biopsied. Therefore, PSMA ligand-based positron emission tomography (PET) has been increasingly utilized for the accurate diagnosis, clinical staging, dynamic monitoring, treatment guidance, and prognosis evaluation of PCa. Moreover, PSMA-targeted radioligand therapy (RLT), antibody-drug conjugate (ADC) therapy, cellular immunotherapy, photodynamic therapy (PDT), and photothermal therapy (PTT), along with PSMA radioguided surgery (PSMA-RGS) intervention, have shown substantial advantages and promising potential. The field of PSMA ligands in PCa management has seen remarkable advancements in recent years, impacting both diagnostic and therapeutic approaches. This review discusses and summarizes the recent research progress and application prospects of PSMA-based theranostics in the clinical management of PCa in Asian populations.

BACKGROUND:Renal ischemia/reperfusion injury (RIRI) is an inevitable consequence of kidney transplantation and has a negative impact on both short-term and long-term graft survival. The identification of key markers in RIRI to improve the prognosis of patients would be highly advantageous. METHODS:Gene expression profile data of GSE27274 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed using the Limma package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of DEGs were performed. Support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression modeling were both performed to identify potential biomarkers. The GSE148420 dataset, quantitative reverse transcriptase-PCR, and western blotting results of kidney tissue samples were used to validate the bioinformatic analysis. Lastly, exploring differences between different groups through gene set enrichment analysis and using DsigDB database to identify potential therapeutic drugs targeting hub genes. RESULTS:A total of 160 upregulated and 180 downregulated DEGs were identified. Functional enrichment analysis identified significant enrichment in processes involving peroxisomes. As a subunit of Polycomb Repressive Complex 1(PRC1), chromobox 6(Cbx6) was identified as a potential biomarker with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval 0.624-1.000) in the validation cohort, and it was highly expressed in the RIRI group (p < 0.05). In the high expression group Cbx6 was more enriched in the toll-like receptor signaling pathway. We predicted 15 potential drugs targeting hub genes of RIRI. CONCLUSIONS:We identified Cbx6 as a potential biomarker for RIRI and 15 potential drugs for the treatment of RIRI, which might shed a light on the treatment of RIRI.

One-for-all phototheranostics that allows the simultaneous implementations of multiple optical imaging and therapeutic modalities by utilizing a single component, is growing into a sparkling frontier in cancer treatment. Of particular interest is phototheranostic agent with emission in the second near-infrared (NIR-II) window. Nevertheless, the practical uses of those conventional NIR-II agents are severely impeded by their unsatisfactory features including insufficient stability, low synthetic yield, to be extended absorption/ emission wavelengths, and inefficient phototheranostic outcomes. Developing exceptional phototheranostic agents is thus highly desirable yet remains formidably challenging. Herein, we synthesized two novel N-heteroacenes-based NIR-II luminogens, namely 2TT-PPT and 4TT-PBPT, by respectively employing pyrene-fused phenaziothiadiazoles and pyrene-fused bisphenaziothiadiazoles as acceptor skeletons. There is strength in numbers by increasing the fusing rings in N-heteroacenes moieties and numbers of appended donors. Compared to less ring-fused 2TT-PPT, the giant molecule 4TT-PBPT shows improved photophysical characteristics, such as enhanced light absorbance, red-shifted wavelengths, higher brightness, favorable reactive oxygen species (ROS) generation, and elevated photothermal conversion efficiency, which render 4TT-PBPT nanoparticles excellent fluorescence-photoacoustic-photothermal trimodal imaging guided photodynamic-photothermal synergistic therapy for orthotopic bladder cancer.

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

BackgroundObservational studies have found a link between two autoimmune diseases, namely, primary sclerosing cholangitis (PSC) and systemic lupus erythematosus (SLE). However, the relationship remains unclear.MethodsBidirectional Mendelian randomization (MR) analysis and statistical methods, including inverse variance weighting, weighted median, and MR-Egger tests, were performed using data from genome-wide association studies to detect a causal relationship between PSC and SLE. Sensitivity analyses were subsequently performed to assess the robustness of the results. Univariate MR methods were also investigated.ResultsResults of MR analysis suggested that PSC was associated with an increased risk for SLE (odds ratio: 1.33, 95% confidence interval: 1.10-1.61, P=0.0039) However, SLE had no significant causal relationship with PSC.ConclusionResults of MR analysis revealed that patients with PSC were at an increased risk for SLE, which provides new insights into the relationship between these two autoimmune diseases.

BackgroundDespite the fact that 1-year graft and recipient survival rates are above 90% in most transplant centers, improving long-term graft survival remains an important challenge. Immunosuppressant nonadherence has been recognized as one of the important risk factors for long-term graft failure. Understanding the modifiable correlates and risk factors for medication non-adherence is essential to develop interventions to improve adherence and thus long-term transplantation outcomes.MethodsThis study conducted a questionnaire survey on 431 renal transplant recipients who were followed up in the outpatient clinic between January 2022 and January 2023, and 409 valid questionnaires were returned. The BAASIS questionnaire was used to assess the prevalence of nonadherence to immunosuppressive therapy (implementation phase) in Chinese renal transplant recipients and to explore the multilevel correlates of immunosuppressive nonadherence. The BAASIS questionnaire was used to categorize renal transplant recipients into adherent (n = 239) and non-adherent (n = 170) groups, and a prospective cohort study with a 1-year follow-up was conducted to explore the impact of immunosuppressant non-adherence on clinical outcomes.ResultsThe prevalence of nonadherence to immunosuppressant therapy in renal transplant recipients in this study was as high as 41.6%. The number of years post-transplant (OR: 1.240, 95% CI: 1.136–1.353, p < 0.001) and the frequency of twice-daily dosing (OR: 5.145, 95% CI: 2.690–9.840, p < 0.001) were positively correlated with immunosuppressive nonadherence. There was a significant difference in TAC IPV (Intra-individual Variability) between the adherent and nonadherent groups (22.7 ± 8.7 vs. 25.4 ± 11.6, p = 0.010). Renal function remained stable during the follow-up period in the recipients in the adherence group and tended to decrease in the recipients in the non-adherence group (F = 4.932, p = 0.001). The rates of graft loss (7.1% vs. 1.7%, p = 0.006) and rejection (12.4% vs. 4.2%, p = 0.002) were higher in the nonadherent group than in the adherent group.ConclusionLonger time post-transplant and higher frequency of immunosuppressive dosing were positively associated with nonadherence to immunosuppressives medication. Immunosuppressant nonadherence was associated with adverse graft outcomes.

Kidney transplantation is the gold standard for the treatment of end-stage renal disease (ESRD). However, the scarcity of kidneys has caused more and more ESRD patients being stuck on the waiting-list for surgery. Improving the survival rate of kidney grafts as much as possible is not only responsible for patients, but also an alternative solution to kidney shortage. Thus, rapid diagnosis and timely management of surgical complications are of vital importance to the success of renal transplantation but lack efficient methods and technologies. Herein, a fluorescence technology based on bright, photostable, and long-circulating aggregation-induced emission (AIE) active NIR-II nano contrast agent for the whole-process monitoring and evaluation of renal transplantation has been reported. The outstanding optical property and long-circulating characteristic of the AIE NPs help to achieve renal angiography in the kidney retrieval surgery, donor kidney quality evaluation before transplantation, diagnosing vascular complications, and assessment of renal graft reperfusion after revascularization, which considerably outperforms the clinically approved indocyanine green (ICG).

Background:Renal ischemia-reperfusion injury (IRI) is an inevitable occurrence during kidney transplantation. Mitophagy, ferroptosis, and the associated immune microenvironment (IME) have been shown to play important roles in renal IRI. However, the role of mitophagy-associated IME genes in IRI remains unclear. In this study, we aimed to construct a prediction model of IRI prognosis based on mitophagy-associated IME genes.Method:The specific biological characteristics of the mitophagy-associated IME gene signature were comprehensively analyzed using public databases such as GEO, Pathway Unification, and FerrDb. Correlations between the expression of prognostic genes and immune-related genes and IRI prognosis were determined by Cox regression, LASSO analysis, and Pearson's correlation. Molecular validation was performed using human kidney 2 (HK2) cells and culture supernatant as well as the serum and kidney tissues of mice after renal IRI. Gene expression was measured by PCR, and inflammatory cell infiltration was examined by ELISA and mass cytometry. Renal tissue damage was characterized using renal tissue homogenate and tissue sections.Results:The expression of the mitophagy-associated IME gene signature was significantly correlated with IRI prognosis. Excessive mitophagy and extensive immune infiltration were the primary factors affecting IRI. In particular, FUNDC1, SQSTM1, UBB, UBC, KLF2, CDKN1A, and GDF15 were the key influencing factors. In addition, B cells, neutrophils, T cells, and M1 macrophages were the key immune cells present in the IME after IRI. A prediction model for IRI prognosis was constructed based on the key factors associated with the mitophagy IME. Validation experiments in cells and mice indicated that the prediction model was reliable and applicable.Conclusion:We clarified the relationship between the mitophagy-related IME and IRI. The IRI prognostic prediction model based on the mitophagy-associated IME gene signature provides novel insights on the prognosis and treatment of renal IRI.

BackgroundWith the improvement of immunosuppressive regimens, the success rate and availability of ABO-incompatible (ABO-i) kidney transplantation (KT) have gradually increased. However, the management of immunosuppression protocols and complications associated with ABO-i KT is complex. Here, we report a clinical case of ABO-i living donor KT with allograft dysfunction caused by acute blood group antibody-dependent rejection triggered by human parvovirus B19 (B19V).Case reportThe ABO blood group of the recipient was O, and that of the donor was B. The recipient had high baseline anti-B antibody titers (IgM, 1:1024; IgG, 1:64). Before transplantation, he completed a desensitization protocol comprising plasma exchange, double-filtration plasmapheresis, and rituximab, which maintained a low blood group antibody level and resulted in successful transplantation. Two weeks after surgery, the recipient developed a B19V infection combined with acute T-cell-mediated rejection. After the anti-rejection regimen, acute rejection (AR) was successfully reversed, but B19V persisted. One week after AR stabilization, the patient experienced acute antibody-mediated rejection that was more severe and refractory, resulting in the loss of the transplanted kidney.ConclusionDesensitization combined with immunosuppressants can lead to overimmunosuppression and cause various infections. Infections could break the accommodation state of the patient, thereby inducing AR and resulting in the loss of the transplanted kidney.

Histone deacetylase 6 (HDAC6), an almost exclusively cytoplasmic enzyme, plays an essential role in many biological processes and exerts its deacetylation-dependent/independent effects on a variety of target molecules, which has contributed to the flourishing growth of relatively isoform-specific enzyme inhibitors. Renal transplantation (RT) is one of the alternatively preferred treatments and the most cost-effective treatment approaches for the great majority of patients with end-stage renal disease (ESRD). HDAC6 expression and activity have recently been shown to be increased in kidney disease in a number of studies. To date, a substantial amount of validated studies has identified HDAC6 as a pivotal modulator of innate and adaptive immunity, and HDAC6 inhibitors (HDAC6i) are being developed and investigated for use in arrays of immune-related diseases, making HDAC6i a promising therapeutic candidate for the management of a variety of renal diseases. Based on accumulating evidence, HDAC6i markedly open up new avenues for therapeutic intervention to protect against oxidative stress–induced damage, tip the balance in favor of the generation of tolerance-related immune cells, and attenuate fibrosis by inhibiting multiple activations of cell profibrotic signaling pathways. Taken together, we have a point of view that targeting HDAC6 may be a novel approach for the therapeutic strategy of RT-related complications, including consequences of ischemia-reperfusion injury, induction of immune tolerance in transplantation, equilibrium of rejection, and improvement of chronic renal graft interstitial fibrosis after transplantation in patients. Herein, we will elaborate on the unique function of HDAC6, which focuses on therapeutical mechanism of action related to immunological events with a general account of the tantalizing potential to the clinic.

Abstract Background Understanding the modifiable correlates and risk factors for medication non-adherence is essential to develop interventions to improve adherence and thus long-term transplantation outcomes. Methods This single-center cross-sectional study collected 409 validated questionnaires of renal transplant recipients followed in outpatient clinics. The incidence of nonadherence to immunosuppressive therapy (implementation phase) was calculated. Multilevel correlates associated with nonadherence were collected to analyze multilevel correlates of nonadherence in kidney transplant recipients. The relationship between nonadherence and recipient outcomes was also explore. Results The incidence of nonadherence to immunosuppressive drugs in renal transplant recipients was 41.6%. Multiple logistic regression analysis showed that 4 variables were positively associated with immunosuppressive nonadherence, namely without steady partner (OR: 1.722; 95%CI: 1.034–2.866), post-transplant years (OR: 1.240; 95%CI: 1.134–1.356), twice-daily immunosuppressive regimen (OR: 5.522 95%CI: 2.857–10.671), Tac IPV (OR: 1.029 95%CI: 1.007–1.052). There was a significant difference in Tac IPV between the adherent and nonadherent groups. The incidence of rejection was 4.2% (10/239) in the adherent group and 12.4% (21/170) in the nonadherent group(p = 0.002). In addition, nonadherence (OR: 2.967, 95%CI: 1.248–7.058) and Tac IPV (OR: 1.030, 95%CI: 1.001–1.060) were positively correlated with episodes of rejection. Conclusion The higher incidence of immunosuppression nonadherence in renal transplant recipients correlates with lacking a steady domestic partner, longer time since the transplantation, higher frequency of immunosuppressive dosing, and higher Tac IPV. In addition, nonadherence and higher tacrolimus IPV were correlated with episodes of rejection. Tacrolimus IPV can be an additional instrument for identifying recipients at risk of nonadherence.