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Background: Benign prostatic hyperplasia (BPH) is a common disease occurring in elderly and middle-aged men, and cardiovascular diseases (CVDs) are one of the major causes of death worldwide. Many observational studies examined have found a strong association between BPH and CVDs, but the causal relationship between them is unclear. The aim of this study was to determine the causal relationship between BPH and CVDs, specifically five diseases: stroke, coronary heart disease (CHD), heart failure, myocardial infarction (MI), and atrial fibrillation (AF). Methods: In this study, we obtained single nucleotide polymorphisms (SNPs) of patients with BPH from the UK Biobank database and patients with CVDs from the UK Biobank, the HERMES Consortium, and the FinnGen Genome Database, each used as a genetic tool for a Mendelian randomization (MR) study. We used conventional MR analysis to assess potential causal direction between BPH and CVDs, as well as MR-Egger, MR-PRESSO, model-based estimation (MBE) and weighted median methods for sensitivity analysis. Results: Using a bidirectional two-sample MR study, we found that BPH patients had an increased risk of developing CHD (ConMix OR = 1.152, 95% CI: 1.011-1.235, p = 0.035) and MI (ConMix OR = 1.107.95% CI: 1.022-1.164, p = 0.013), but a decreased risk of stroke (ConMix OR = 0.872, 95% CI: 0.797-0.926, p = 0.002). The reverse study was not statistically significant and further research may be needed. Conclusion: Our study suggests a potential causal relationship between BPH and CVDs. BPH appears to be a risk factor for CHD and MI, but it may be protective against stroke. There was no evidence of a causal association in the reverse study, and a larger sample size was needed in follow-up to further explore the potential association.
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Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.
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Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation.
Assuntos
Biblioteca de Peptídeos , Espectrometria de Massas em Tandem , Peptídeos/farmacologia , Peptídeos/químicaRESUMO
Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy. Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard. Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01). Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.
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Delivering cargo molecules across the plasma membrane is critical for biomedical research, and the need to develop molecularly well-defined tags that enable cargo transportation is ever-increasing. We report here a hydrophilic endocytosis-promoting peptide (EPP6) rich in hydroxyl groups with no positive charge. EPP6 can transport a wide array of small-molecule cargos into a diverse panel of animal cells. Mechanistic studies revealed that it entered the cells through a caveolin- and dynamin-dependent endocytosis pathway, mediated by the surface receptor fibrinogen C domain-containing protein 1. After endocytosis, EPP6 trafficked through early and late endosomes within 30 min. Over time, EPP6 partitioned among cytosol, lysosomes, and some long-lived compartments. It also demonstrated prominent transcytosis abilities in both in vitro and in vivo models. Our study proves that positive charge is not an indispensable feature for hydrophilic cell-penetrating peptides and provides a new category of molecularly well-defined delivery tags for biomedical applications.