-
1.
Tenapanor in Chinese ESRD patients with hyperphosphatemia on haemodialysis: a randomised, phase 3 trial.
Gan, L, Xing, L, Xu, Y, Zhou, L, Jiang, H, Sun, X, Guan, T, Luo, P, Wang, J, Sun, F, et al
Clinical kidney journal. 2024;(1):sfad216
Abstract
BACKGROUND The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). METHODS This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. RESULTS Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. CONCLUSIONS Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.
-
2.
Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients.
Wang, X, Zeng, M, Ju, X, Lin, A, Zhou, C, Shen, J, Liu, Z, Tang, B, Cheng, Q, Wang, Y, et al
The British journal of surgery. 2024;(1)
Abstract
BACKGROUND Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.
-
3.
Ferroptosis in age-related vascular diseases: Molecular mechanisms and innovative therapeutic strategies.
Dai, Y, Wei, X, Jiang, T, Wang, Q, Li, Y, Ruan, N, Luo, P, Huang, J, Yang, Y, Yan, Q, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:116356
Abstract
Aging, an inevitable aspect of human existence, serves as one of the predominant risk factors for vascular diseases. Delving into the mystery of vascular disease's pathophysiology, the profound involvement of programmed cell death (PCD) has been extensively demonstrated. PCD is a fundamental biological process that plays a crucial role in both normal physiology and pathology, including a recently discovered form, ferroptosis. Ferroptosis is characterized by its reliance on iron and lipid peroxidation, and its significant involvement in vascular disease pathophysiology has been increasingly acknowledged. This phenomenon not only offers a promising therapeutic target but also deepens our understanding of the complex relationship between ferroptosis and age-related vascular diseases. Consequently, this article aims to thoroughly review the mechanisms that enable the effective control and inhibition of ferroptosis. It focuses on genetic and pharmacological interventions, with the goal of developing innovative therapeutic strategies to combat age-related vascular diseases.
-
4.
Viral oncogenes, viruses, and cancer: a third-generation sequencing perspective on viral integration into the human genome.
Ye, R, Wang, A, Bu, B, Luo, P, Deng, W, Zhang, X, Yin, S
Frontiers in oncology. 2023;:1333812
Abstract
The link between viruses and cancer has intrigued scientists for decades. Certain viruses have been shown to be vital in the development of various cancers by integrating viral DNA into the host genome and activating viral oncogenes. These viruses include the Human Papillomavirus (HPV), Hepatitis B and C Viruses (HBV and HCV), Epstein-Barr Virus (EBV), and Human T-Cell Leukemia Virus (HTLV-1), which are all linked to the development of a myriad of human cancers. Third-generation sequencing technologies have revolutionized our ability to study viral integration events at unprecedented resolution in recent years. They offer long sequencing capabilities along with the ability to map viral integration sites, assess host gene expression, and track clonal evolution in cancer cells. Recently, researchers have been exploring the application of Oxford Nanopore Technologies (ONT) nanopore sequencing and Pacific BioSciences (PacBio) single-molecule real-time (SMRT) sequencing in cancer research. As viral integration is crucial to the development of cancer via viruses, third-generation sequencing would provide a novel approach to studying the relationship interlinking viral oncogenes, viruses, and cancer. This review article explores the molecular mechanisms underlying viral oncogenesis, the role of viruses in cancer development, and the impact of third-generation sequencing on our understanding of viral integration into the human genome.
-
5.
Oxalate as a potent promoter of kidney stone formation.
Chen, T, Qian, B, Zou, J, Luo, P, Zou, J, Li, W, Chen, Q, Zheng, L
Frontiers in medicine. 2023;:1159616
Abstract
Kidney stones are among the most prevalent urological diseases, with a high incidence and recurrence rate. Treating kidney stones has been greatly improved by the development of various minimally invasive techniques. Currently, stone treatment is relatively mature. However, most current treatment methods are limited to stones and cannot effectively reduce their incidence and recurrence. Therefore, preventing disease occurrence, development, and recurrence after treatment, has become an urgent issue. The etiology and pathogenesis of stone formation are key factors in resolving this issue. More than 80% of kidney stones are calcium oxalate stones. Several studies have studied the formation mechanism of stones from the metabolism of urinary calcium, but there are few studies on oxalate, which plays an equally important role in stone formation. Oxalate and calcium play equally important roles in calcium oxalate stones, whereas the metabolism and excretion disorders of oxalate play a crucial role in their occurrence. Therefore, starting from the relationship between renal calculi and oxalate metabolism, this work reviews the occurrence of renal calculi, oxalate absorption, metabolism, and excretion mechanisms, focusing on the key role of SLC26A6 in oxalate excretion and the regulatory mechanism of SLC26A6 in oxalate transport. This review provides some new clues for the mechanism of kidney stones from the perspective of oxalate to improve the understanding of the role of oxalate in the formation of kidney stones and to provide suggestions for reducing the incidence and recurrence rate of kidney stones.
-
6.
Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.
Wang, Y, Chen, X, Zhu, H, Guo, Z, Yang, Y, Luo, P, He, Y, Xu, Y, Ji, D, Gao, X, et al
American journal of nephrology. 2023;(11-12):479-488
Abstract
INTRODUCTION Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.
-
7.
Highly sensitive surface plasmon resonance sensor with surface modified MoSe2/ZnO composite film for non-enzymatic glucose detection.
Chen, R, Guo, C, Lan, G, Luo, P, Yi, J, Wei, W
Biosensors & bioelectronics. 2023;:115469
Abstract
The rapid and accurate assessment of glucose concentration has been demonstrated to play a significant role in human health, such as the diagnosis and treatment of diabetes, pharmaceutical research and quality monitoring in the food industry, necessitating further development of the performance for glucose sensor especially at low concentrations. However, glucose oxidase-based sensors suffer from crucial restriction in bioactivity because of their poor environmental tolerance. Recently, catalytic nanomaterials with enzyme-mimicking activity, known as nanozymes, have gained considerable interest to overcome the drawback. In this scenario, we report an inspiring surface plasmon resonance (SPR) sensor for non-enzymatic glucose detection employing ZnO nanoparticles and MoSe2 nanosheets composite (MoSe2/ZnO) as sensing film, featuring desirable advantages of high sensitivity and selectivity, lab-free and low cost. The ZnO was used to specifically recognize and bind glucose, and further signal amplification was realized by incorporating of MoSe2 owing to its larger specific surface area and favorable bio-compatibility, as well as high electron mobility. These unique features of MoSe2/ZnO composite film result in an obvious improvement of sensitivity for glucose detection. Experimental results show that the measurement sensitivity of the proposed sensor could reach 72.17 nm/(mg/mL) and a detection limit of 4.16 μg/mL by appropriately optimizing the componential constitutions of MoSe2/ZnO composite. In addition, the favorable selectivity, repeatability and stability are demonstrated as well. This facile and cost-effective work provides a novel strategy for constructing high-performance SPR sensor for glucose detection and a prospective application in biomedicine and human health monitoring.
-
8.
Randomized Phase 2 Trial of Telitacicept in Patients With IgA Nephropathy With Persistent Proteinuria.
Lv, J, Liu, L, Hao, C, Li, G, Fu, P, Xing, G, Zheng, H, Chen, N, Wang, C, Luo, P, et al
Kidney international reports. 2023;(3):499-506
Abstract
INTRODUCTION To date, no specific therapies have been approved for immunoglobulin A nephropathy (IgAN) treatment. Telitacicept is a fusion protein composed of transmembrane activator and calcium-modulating cyclophilin ligand interactor and fragment crystallizable portion of immunoglobulin G (IgG), which neutralizes the B lymphocyte stimulator and a proliferation-inducing ligand. METHODS This phase 2 randomized placebo-controlled trial aimed to evaluate the efficacy and safety of telitacicept in patients with IgAN. Participants with an estimated glomerular filtration rate (eGFR) >35 ml/min per 1.73 m2 and proteinuria ≥0.75 g/d despite optimal supportive therapy, were randomized 1:1:1 to receive subcutaneous telitacicept 160 mg, telitacicept 240 mg, or placebo weekly for 24 weeks. The primary end point was the change in 24-hour proteinuria at week 24 from baseline. RESULTS Forty-four participants were randomized into placebo (n = 14), telitacicept 160 mg (n = 16), and telitacicept 240 mg (n = 14) groups. Continuous reductions in serum IgA, IgG, and IgM levels were observed in the telitacicept group. Telitacicept 240 mg therapy reduced mean proteinuria by 49% from baseline (change in proteinuria vs. placebo, 0.88; 95% confidence interval, -1.57 to -0.20; P = 0.013), whereas telitacicept 160 mg reduced it by 25% (-0.29; 95% confidence interval, -0.95 to 0.37; P = 0.389). The eGFR remained stable over time. Adverse events (AEs) were similar in all groups. Treatment-emergent AEs were mild or moderate, and no severe AEs were reported. CONCLUSION Telitacicept treatment led to a clinically meaningful reduction in proteinuria in patients with IgAN in the present phase 2 clinical trial. This effect is indicative of a reduced risk for future kidney disease progression.
-
9.
The Roles of GRETCHEN HAGEN3 (GH3)-Dependent Auxin Conjugation in the Regulation of Plant Development and Stress Adaptation.
Luo, P, Li, TT, Shi, WM, Ma, Q, Di, DW
Plants (Basel, Switzerland). 2023;(24)
Abstract
The precise control of free auxin (indole-3-acetic acid, IAA) gradient, which is orchestrated by biosynthesis, conjugation, degradation, hydrolyzation, and transport, is critical for all aspects of plant growth and development. Of these, the GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetase family, pivotal in conjugating IAA with amino acids, has garnered significant interest. Recent advances in understanding GH3-dependent IAA conjugation have positioned GH3 functional elucidation as a hot topic of research. This review aims to consolidate and discuss recent findings on (i) the enzymatic mechanisms driving GH3 activity, (ii) the influence of chemical inhibitor on GH3 function, and (iii) the transcriptional regulation of GH3 and its impact on plant development and stress response. Additionally, we explore the distinct biological functions attributed to IAA-amino acid conjugates.
-
10.
Facile synthesis of curcumin-containing poly(amidoamine) dendrimers as pH-responsive delivery system for osteoporosis treatment.
Yang, X, Kuang, Z, Yang, X, Hu, X, Luo, P, Lai, Q, Zhang, B, Zhang, X, Wei, Y
Colloids and surfaces. B, Biointerfaces. 2023;:113029
Abstract
Osteoporosis is an age-related metabolic disease of bone, resulting in bone pain and even bone fragility and brittle fracture. Inhibiting overactive osteoclasts while promoting osteoblast activity is an ideal way to treat osteoporosis. Previous studies have demonstrated that natural compounds, such as curcumin (Cur) have dual roles both in promoting bone formation and inhibiting bone resorption, making them promising candidates for osteoporosis treatment. However, their poor water solubility, high dosage of curative effect and significant toxicity to other organs have largely limited their clinical translations. In this study, a novel method was reported to conjugate Cur and poly(amidoamine) dendrimers (PAD) using hexachlorocyclotriphosphazene (HCCP) as the linkage through a one-pot reaction, forming stable and uniform Cur loaded nanospheres (HCCP-Cur-PAD, HCP NPs). Owing to the hydrophilicity of PAD and hydrophobicity of Cur, HCP NPs can self-assemble into nanoparticles with particle size of 138.8 ± 78.7 nm and display excellent water dispersity. The loading capacity of Cur can reach 27.2% and it can be released from HCP NPs with pH-responsiveness. In vitro experimental results demonstrated that the HCP NPs entered lysosomes by endocytosis and proved dual anti-osteoporosis effects of inhibiting osteoclasts and promoting osteoblasts.