Exenatide reduces atrial fibrillation susceptibility by inhibiting hKv1.5 and hNav1.5 channels.

Exenatide, a promising cardioprotective agent, protects against cardiac structural remodeling and diastolic dysfunction. Combined blockade of sodium and potassium channels is valuable for managing atrial fibrillation (AF). Here, we explored whether exenatide displayed anti-AF effects by inhibiting human Kv1.5 and Nav1.5 channels. We used the whole-cell patch-clamp technique to investigate the effects of exenatide on hKv1.5 and hNav1.5 channels expressed in human embryonic kidney 293 cells and studied the effects of exenatide on action potential (AP) and other cardiac ionic currents in rat atrial myocytes. Additionally, an electrical mapping system was used to explore the effects of exenatide on electrical properties and AF activity in isolated rat hearts. Finally, a rat AF model, established using acetylcholine and calcium chloride, was employed to evaluate the anti-AF potential of exenatide in rats. Exenatide reversibly suppressed IKv1.5 with IC50 of 3.08 µM, preferentially blocked the hKv1.5 channel in its closed state, and positively shifted the voltage-dependent activation curve. Exenatide also reversibly inhibited INav1.5 with IC50 of 3.30 µM, negatively shifted the voltage-dependent inactivation curve, and slowed its recovery from inactivation with significant use-dependency at 5 and 10 Hz. Furthermore, exenatide prolonged AP duration and suppressed the sustained K+ current (Iss) and transient outward K+ current (Ito), but without inhibition of L-type Ca2+ current (ICa,L) in rat atrial myocytes. Exenatide prevented AF incidence and duration in rat hearts and rats. These findings demonstrate that exenatide inhibits IKv1.5 and INav1.5in vitro and reduces AF susceptibility in isolated rat hearts and rats.

KN-93 promotes HDAC4 nucleus translocation to promote fatty acid oxidation in myocardial infarction.

Myocardial infarction (MI) is a potentially fatal disease that causes a significant number of deaths worldwide. The strategy of increasing fatty acid oxidation in myocytes is considered a therapeutic avenue to accelerate metabolism to meet energy demands. We conducted the study aiming to investigate the effect of KN-93, which induces histone deacetylase (HDAC)4 shuttling to the nucleus, on fatty acid oxidation and the expression of related genes. A mouse model of myocardial infarction was induced by isoprenaline administration. Heart damage was assessed by the detection of cardiac injury markers. The level of fatty acid oxidation level was evaluated by testing the expression of related genes. Both immunofluorescence and immunoblotting in the cytosol or nucleus were utilized to observe the distribution of HDAC4. The interaction between HDAC4 and specificity protein (SP)1 was confirmed by co-immunoprecipitation. The acetylation level of SP1 was tested after KN-93 treatment and HDAC4 inhibitor. Oxygen consumption rate and immunoblotting experiments were used to determine whether the effect of KN-93 on increasing fatty acid oxidation is through HDAC4 and SP1. Administration of KN-93 significantly reduced cardiac injury in myocardial infarction and promoted fatty acid oxidation both in vitro and in vivo. KN-93 was shown to mediate nuclear translocation of HDAC4. HDAC4 was found to interact with SP1 and reduce SP1 acetylation. HDAC4 or SP1 inhibitors attenuated the effect of KN-93 on fatty acid oxidation. In conclusion, KN-93 promotes HDAC4 translocation to the nucleus, thereby potentially enhancing fatty acid oxidation by SP1.

A water quality assessment model involving novel fluorescence technology.

The reasonable utilization of water resources and real-time monitoring of water pollution are the core tasks of current world hydrological and water conservancy work. Novel technologies and methods for monitoring water pollution are important means to ensure water health. However, the absence of intuitive and simple analysis methods for the assessment of regional pollution in large-scale water bodies has prevented scientists from quickly grasping the overall situation of water pollution. In this study, we propose a strategy based on the unique combination of fluorescence technology and simple kriging (SK) interpolation (FL-SK) for the first time. This strategy could present the relative magnitude and distribution of the physicochemical indicators of a whole natural lake intuitively and accurately. The unique FL-SK model firstly offers a simple and effective water quality method that provides the pollution index of different sampling points in lakes. The macroscopic evaluation of large-scale water bodies by the FL-SK model primarily relies on the fluorescence response of the RDM-TPE to the comprehensive indicators of the water body, as experimental results have revealed a good correlation between fluorescent responses and six normalized physicochemical indicators. Multiple linear regression and fluorescence response experiments on RDM-TPE indicate that to some extent, the fluorescence signals of the FL-SK model may originate from a certain type of sulfide in the water body. Pattern discovery could enable the analysis of pollution levels in other ecosystems and promote early pollution assessment in the future.

A rare case of daratumumab-associated encephalopathy in multiple myeloma.

Aim: Daratumumab, a CD38 monoclonal antibody, has been widely used in patients with multiple myeloma. Although a variety of adverse events have been reported, consciousness impairment has not been reported yet. We report a case of encephalopathy associated with daratumumab. Case presentation: A 57-year-old male, diagnosed with relapsed multiple myeloma, was treated with daratumumab. He developed a loss of consciousness after the first administration. Cerebral spinal fluid and magnetic resonance imaging of the brain suggested encephalopathy. Conclusion: It is recommended to be aware of rare but life threatening side effects of daratumumab. We present a case of rare encephalopathy characterized by consciousness disorder associated with daratumumab, which was successfully resolved on prompt institution of steroids, although the mechanism was unknown.

Daratumumab is a drug. It is used to treat multiple myeloma. Many patients use this drug. It has many side effects. But consciousness disorder is rare. A 57-year-old male was diagnosed with multiple myeloma. He was treated with daratumumab. He became unconscious after this treatment. Steroids helped his recovery.

A real-world pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) events for Bruton's tyrosine kinase inhibitors (BTKis) single and its combination therapy.

BACKGROUND: Bruton's tyrosine kinase inhibitors (BTKis) are targeted treatments for B-cell tumors but have significant side effects. This study assesses and contrasts the side effects of BTKis alone and its four combination therapies. RESEARCH DESIGN AND METHODS: The reporting odds ratio (ROR) was used to analyze the data on three BTKis monotherapies and combinations of ibrutinib with rituximab, obinutuzumab, venetoclax, and lenalidomide in the FDA Adverse Event Reporting System (FAERS) database up to December 2022. RESULTS: We analyzed the top 20 PTs for each treatment regimen. In monotherapies, atrial fibrillation (ROR (95% CI): 9.88 (9.47-10.32)) in zanubrutinib and rash (6.97 (5.42-8.98)) in acalabrutinib had higher associations. In combinations, infection (6.86 (6.11-7.70)), atrial fibrillation (27.96 (22.61-34.58)) and myelosuppression (10.09 (8.89-11.46)) were vital signals when ibrutinib was combined with obinutuzumab, and pyrexia (4.22 (2.57-6.93)) had a high signal value when combined with lenalidomide. Hemorrhage had a lower signal value when combined with venetoclax compared to ibrutinib alone (2.50 (2.18-2.87) vs 3.60 (3.52-3.68)). CONCLUSIONS: The ibrutinib-obinutuzumab combo has the highest risk of infection, atrial fibrillation, and myelosuppression, and the ibrutinib-lenalidomide combo has the highest risk of pyrexia. However, the ibrutinib-venetoclax combo has a lower risk of hemorrhage than monotherapy.

Recidivas en pacientes de Lepra MB tratados con 24 meses de MDT en el suroeste de China: Un informe breve / No disponible

Este estudio evalúa el índice de recidivas entre los pacientes de lepra tratados con 24 meses de MDT en el suroeste de China. Para ello se llevó a cabo un estudio retrospectivo de recidivas en esta parte del país. Se diseñó un cuestionario muy detallado para recoger los datos sobre las recidivas entre pacientes MB que habían completado 2 años de tratamiento OMS/MB desde 1989 a 2000. Los datos se obtuvieron sobre 2.517 pacientes multibacilares en 27 países del suroeste de China. Entre los 2.517 pacientes MB, 235 pacientes fallecieron o se dieron de baja durante el seguimiento y 2.374 fueron controlados durante más de 3 años después de completar la MDT. La duración total del seguimiento fue de 20,825 personas-año, con una duración media de 8.27 años por paciente. Se identificaron cinco pacientes con recidivas con un índice acumulado de recidivas de 0-21/1.000 personas-año. Los IB iníciales variaron entre 1.8 a 5. Las recidivas se presentaron entre 48-158 mese después de completar la MDT. El índice de recidivas de los pacientes MB tratados con 24 meses con una pauta OMS/MB se consideró muy bajo después de un largo período de seguimiento

This study investigates the relapse rate among multibacillary leprosy patients treated with 24 months of MDT in south west China. A retrospective relapse survey was conducted in the southwest of China. A detailed questionnaire was designed to collect the data on relapse among MB patients who completed 2 years of the WHO/MB regimen, from 1989 to 2000. The data about 2.517 multibacillary leprosy patients in 27 counties in the southwest of China were collected. Among 2.517 MB patients, 235 patients died or were lost to follow-up and 2.374 were followed up for more than 3 years after completion of MDT. The total duration of follow-up was 20,825 person-years, with a mean duration of 8.27 years per patient. Five patients with relapse were identified with an accumulated relapse rate of 0.21-/1.000 person-years. Their initial Bls ranged from 1.8 to 5. The patients with relapse occurred 48-158 months after the completion of MDT. The relapse rate of MB patients treated with 24 months of the WHO/MB regimen was observed to be very low after long-term follow-up

Recidivas en pacientes de Lepra MB tratados con 24 meses de MDT en el suroeste de China: Un informe breve / No disponible

Este estudio evalúa el índice de recidivas entre los pacientes de lepra tratados con 24 meses de MDT en el suroeste de China. Para ello se llevó a cabo un estudio retrospectivo de recidivas en esta parte del país. Se diseñó un cuestionario muy detallado para recoger los datos sobre las recidivas entre pacientes MB que habían completado 2 años de tratamiento OMS/MB desde 1989 a 2000. Los datos se obtuvieron sobre 2.517 pacientes multibacilares en 27 países del suroeste de China. Entre los 2.517 pacientes MB, 235 pacientes fallecieron o se dieron de baja durante el seguimiento y 2.374 fueron controlados durante más de 3 años después de completar la MDT. La duración total del seguimiento fue de 20,825 personas-año, con una duración media de 8.27 años por paciente. Se identificaron cinco pacientes con recidivas con un índice acumulado de recidivas de 0-21/1.000 personas-año. Los IB iníciales variaron entre 1.8 a 5. Las recidivas se presentaron entre 48-158 mese después de completar la MDT. El índice de recidivas de los pacientes MB tratados con 24 meses con una pauta OMS/MB se consideró muy bajo después de un largo período de seguimiento (AU)

This study investigates the relapse rate among multibacillary leprosy patients treated with 24 months of MDT in south west China. A retrospective relapse survey was conducted in the southwest of China. A detailed questionnaire was designed to collect the data on relapse among MB patients who completed 2 years of the WHO/MB regimen, from 1989 to 2000. The data about 2.517 multibacillary leprosy patients in 27 counties in the southwest of China were collected. Among 2.517 MB patients, 235 patients died or were lost to follow-up and 2.374 were followed up for more than 3 years after completion of MDT. The total duration of follow-up was 20,825 person-years, with a mean duration of 8.27 years per patient. Five patients with relapse were identified with an accumulated relapse rate of 0.21-/1.000 person-years. Their initial Bls ranged from 1.8 to 5. The patients with relapse occurred 48-158 months after the completion of MDT. The relapse rate of MB patients treated with 24 months of the WHO/MB regimen was observed to be very low after long-term follow-up (AU)