Impact of intra-patient variability of tacrolimus on allograft function and CD4 + /CD8 + ratio in kidney transplant recipients: a retrospective single-center study.

BACKGROUND: Tacrolimus is a critical component of immunosuppressive therapy for kidney transplant recipients. Intra-patient variation (IPV) of tacrolimus levels affects the function of transplanted kidney. AIM: This study aimed to investigate the impact of tacrolimus IPV on kidney function, examine its association with post-transplant duration, and assess its effect on the immune status of transplant recipients. METHOD: This retrospective study was conducted from January 2016 to February 2022. IPV was evaluated using the coefficient of variation (CV) of tacrolimus trough levels from 6 to 48 months after transplantation. Patients were divided into low- and high-IPV groups based on the median CV. Significant differences in kidney function, CD4 + /CD8 + ratio, and post-transplant duration between these groups were analyzed. RESULTS: Among 189 patients, tacrolimus IPV showed a strong correlation with serum creatinine clearance rate (Ccr) and estimated glomerular filtration rate (eGFR) (p < 0.05). Tacrolimus IPV was significantly correlated with post-transplant duration in only two patients (p < 0.05). Using a median CV of 15.4% to categorize patients, the high IPV group, compared to the low IPV group, exhibited significantly higher eGFR at 6-9 months (p < 0.05), lower Ccr at 9-12 months (p < 0.05), and reduced Ccr and eGFR at 15-18 months (p < 0.05). Six months after transplantation, the high IPV group had a significantly lower CD4 + /CD8 + ratio than the low IPV group (p < 0.05). CONCLUSION: This study highlights the significant impact of tacrolimus IPV on transplant kidney function and immune status in transplant patients at various post-transplantation intervals.

Discovery of Novel Imidazo[4,5-c]quinoline Derivatives to Treat Inflammatory Bowel Disease (IBD) by Inhibiting Multiple Proinflammatory Signaling Pathways and Restoring Intestinal Homeostasis.

As a complex pathogenesis driven by immune inflammatory factors and intestinal microbiota, the treatment of inflammatory bowel disease (IBD) may rely on the comprehensive regulation of these important pathogenic factors to reach a favorable therapeutic effect. In the current study, we discovered a series of imidazo[4,5-c]quinoline derivatives that potently and simultaneously inhibited two primary proinflammatory signaling pathways JAK/STAT and NF-κB. Especially, lead compound 8l showed potent inhibitory activities against interferon-stimulated genes (IC50: 3.3 nM) and NF-κB pathways (IC50: 150.7 nM) and decreased the release of various proinflammatory factors at the nanomolar level, including IL-6, IL-8, IL-1ß, TNF-α, IL-12, and IFN-γ. In vivo, 8l produced a strong anti-inflammatory activity in both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute enteritis models and restored the structural composition of gut microbiota. Collectively, this study provided valuable lead compounds for the treatment of IBD and revealed the great anti-inflammatory potential of the simultaneous suppression of JAK/STAT and NF-κB signals.

In situ construction of sulfated TiO2 nanoparticles with TiOSO4 for enhanced photocatalytic hydrogen production.

Photocatalytic hydrogen production from water is a promising method to obtain clean energy in the future. In this work, the sulfated TiO2 photocatalyst is successfully constructed in situ via a soft-templated method for photocatalytic water splitting to produce hydrogen. The content of sulfate species in TiO2 can be tuned by changing the amount of the surfactant. The photocatalyst with the appropriate content of sulfate ions exhibits an apparent quantum efficiency (AQE) of 3.9% at 365 nm and a high hydrogen production rate of 24.32 mmol h-1 g-1, which is 1.65 times that of commercial TiO2 (P25). The optimized photocatalyst has excellent photocatalytic activity for hydrogen evolution benefitting from the presence of sulfate ions on the surface of TiO2, large surface area and oxygen vacancies, which facilitates the rapid migration of photo-generated electrons to its surface and the improvement of the separation efficiency of photo-generated carriers. This work may inspire the rational design and the development of high-efficiency photocatalysts.

Selaginella convolute extract mediated synthesis of ZnO NPs for pain management in emerging nursing care.

Zinc oxide (ZnO), an inorganic metal oxide established in the form of nanoparticles, has considerable biological properties. The current research uses Selaginella convolute (S. convolute) leaf extract to establish ZnO NPs and to assess their use in pain management. S. Convolute leaf extract mediated ZnO NPs were characterized by modern techniques and instruments such as Fourier transforms infrared spectroscopy (FTIR), electron microscopy, X-ray diffraction (XRD), and Ultraviolet-vis-spectroscopy (UV-vis), energy dispersive X-ray spectroscopy (EDX), indicating the emergence of spherical NPs of which is around 40 nm. The FTIR spectrum also signified that S. convolute plant extract polyphenols acted as a capping ligand for the fabricated ZnO NPs. Possessed ZnO NPs have shown important characteristics of muscle relaxing and antinociceptive. A concentration dependent acetic acid induced writhing effect was noted for both S. convolute extract and ZnO NPs. S. convolute plant extract and ZnO NPs are found to exhibit highest muscle relaxation effect in both traction and chimney tests and no sedative effect was shown by both ZnO NPs and plant extract. The present results showed that the S. convolute leaves extract is a very effective green reducing agent for the preparation of ZnO NPs and the prepared NPs can be used in pain management in emerging nursing care in future.