Normal Function Research Articles

Study on the estradiol degradation gene expression and resistance mechanism of Rhodococcus R-001 under low-temperature stress

Estradiol (E2), an endocrine disruptor, acts by mimicking or interfering with the normal physiological functions of natural hormones within organisms, leading to issues such as endocrine system disruption. Notably, seasonal fluctuations in environmental temperature may influence the degradation speed of estradiol (E2) in the natural environment , intensifying its potential health and ecological risks. Therefore, this study aims to explore how bacteria can degrade E2 under low-temperature conditions, unveiling their resistance mechanisms, with the goal of developing new strategies to mitigate the threat of E2 to health and ecological safety. In this paper, we found that Rhodococcus equi DSSKP-R-001 (R-001) can efficiently degrade E2 at 30°C and 10°C. Six genes in R-001 were shown to be involved in E2 degradation by heterologous expression at 30°C. Among them, 17β-HSD, KstD2, and KstD3, were also involved in E2 degradation at 10°C; KstD was not previously known to degrade E2. RNA-seq was used to characterize differentially expressed genes (DEGs) to explore the stress response of R-001 to low-temperature environments to elucidate the strain’s adaptation mechanism. At the low temperature, R-001 cells changed from a round spherical shape to a long rod or irregular shape with elevated unsaturated fatty acids and were consistent with the corresponding genetic changes. Many differentially expressed genes linked to the cold stress response were observed. R-001 was found to upregulate genes encoding cold shock proteins, fatty acid metabolism proteins, the ABC transport system, DNA damage repair, energy metabolism and transcriptional regulators. In this study, we demonstrated six E2 degradation genes in R-001 and found for the first time that E2 degradation genes have different expression characteristics at 30°C and 10°C. Linking R-001 to cold acclimation provides new insights and a mechanistic basis for the simultaneous degradation of E2 under cold stress in Rhodococcus adaptation.

Pilot study to know the best doses of ginseng bulk and its nanoparticles in normal testicular function of rats

Pilot study to know the best doses of ginseng bulk and its nanoparticles in normal testicular function of rats

TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates.

TP53 mutations are found in 5%-10% of de novo myelodysplastic syndrome (MDS) and AML cases. By contrast, in therapy related MDS and AML, mutations in TP53 are found in up to 30%-40% of patients. The majority of inactivating mutations observed in MDS and AML are missense mutations localized in a few prevalent hotspots. TP53 missense mutations together with truncating mutations or chromosomal loss of TP53 determine a loss-of-function effect on normal p53 function. Clonal expansion of TP53-mutant clones is observed under the selection pressure of chemotherapy or MDM2 inhibitor therapy. TP53-mutant clones are resistant to current chemotherapy, and when responses to treatment have been observed, they have correlated poorly with overall survival. The most heavily investigated and targeted agent for patients with TP53-mutant MDS and AML has been APR-246 (eprenetapopt) a p53 reactivator, in combination with azacitidine, but also in triplets with venetoclax. Despite positive results in phase II trials, a phase III trial did not confirm superior response or improved survival. Other agents, like magrolimab (anti-CD47 antibody), failed to demonstrate improved activity in TP53-mutant MDS and AML. Agents whose activity is not dependent on a functional apoptosis system like anti-CD123 antibodies or cellular therapies are in development and may hold promises. Delivering prognostic information in a dismal disease like TP53-mutated MDS and AML is particularly challenging. The physician should balance hope and realism, describing the trajectory of possible treatments and at the same time indicating the poor outcome, together with promoting adaptive coping in patients and elaborating on the nature of the disease.

Doxorubicin induces phosphorylation of lamin A/C and loss of nuclear membrane integrity: A novel mechanism of cardiotoxicity

Lamin A/C, essential inner nuclear membrane proteins, have been linked to progeria, a disease of accelerated aging, and many other diseases, which include cardiac disorder. Lamin A/C mutation and its phosphorylation are associated with altering nuclear shape and size. The role of lamin A/C in regulating normal cardiac function was reported earlier. In the present study, we hypothesized that Doxorubicin (Dox) may alter total lamin A/C expression and phosphorylation, thereby taking part in cardiac injury. An in vitro cellular injury model was generated with Dox (0.1–10.0 μM) treatment on cardiomyoblast cells (H9c2) to prove our hypothesis. Increased size and irregular (ameboid) nucleus shape were observed in H9c2 cells after Dox treatment. Similarly, we have observed a significant increase in cell death on increasing the Dox concentration. The expression of lamin A/C and its phosphorylation at serine 22 significantly decreased and increased, respectively in H9c2 cells and rat hearts after Dox exposure. Phosphorylation led to depolymerization of the lamin A/C in the inner nuclear membrane and was evidenced by their presence throughout the nucleoplasm as observed by immunocytochemistry techniques. Thinning and perforation on the walls of the nuclear membrane were observed in Dox-treated H9c2 cells. LMNA-overexpression in H9c2 protected the cells from Dox-induced cell death, reversing all changes described above. Further, improvement of lamin A/C levels was observed in Dox-treated H9c2 cells when treated with Purvalanol A, a CDK1 inhibitor and N-acetylcysteine, an antioxidant. The study provides new insight regarding Dox-induced cardiac injury with the involvement of lamin A/C and alteration of inner nuclear membrane structure.

Nutraceuticals: New Perspective and Approach to Prevent Dysmenorrhea

Background: The words "nutrition" and "pharmaceutical" are combined to form the phrase "nutraceutical." Nutraceuticals are foods or dietary components that have an important role in regulating and sustaining normal physiological function in humans. For the treatment of dysmenorrhoea, a variety of pharmacological medications are available, however, they all have significant side effects. Dietary supplements and lifestyle management, on the other hand, were found to have a major influence on the occurrence and control of dysmenorrhea. Objective: The objective of this paper is to study a comprehensive review of the dietary and nutritional supplements with special emphasis on dysmenorrhea. This paper focuses on understanding and interpreting the details of menstrual pain and its effective nutritional diet that can be used as a treatment for avoiding menstrual discomfort. Methods: The selection of data has been done by studying a combination of various research and review papers from different databases like PubMed, NCBI, Science Direct, WHO, Cochrane Library, and Web of Science from the year 2000-2022. Results: Based on various papers and literature reviews, we have concluded about various dietary supplements and herbs that can be used to avoid pain during mensuration followed by its all-daily requirement of nutrition on different age groups and efficacy of treatments. Conclusion: According to current evidence, young women should be instructed in the proper use of dietary supplements, nutrition, and vitamins, as well as the inclusion of effective diet and lifestyle changes such as exercise and a well-balanced diet with adequate nutrition, as these are likely to reduce the negative effects of dysmenorrhea.

Left Atrial Peak Systolic Strain as an Indicator Pathway of Diastolic Dysfunction of the Left Ventricle.

Left atrial peak systolic strain (LA-PSS) imaging is an emerging index of left atrial function, and it was shown to be decreased in heart failure with preserved ejection fraction (EF). We aimed to determine whether LA-PSS could be used as an additional diagnostic parameter to current existing guidelines for the presence of left ventricle diastolic dysfunction (LVDD). A total of 190 consecutive adult patients with cardiovascular risk factors and normal left ventricle EF with no prior history of heart failure were included in the study. Speckle tracking software was used to study ventricular parietal deformity, left ventricle global longitudinal systolic strain, and LA-PSS. The median left ventricle global longitudinal systolic strain was -19%, with a significant difference ( P < 0.001) between patients with normal diastolic function versus those with LVDD. The median LA-PSS was 33% (30% to 38%) ( P < 0.001). Most patients (61%) had grade 1 atrial dysfunction based on PSS (range 24%-35%). The analysis of the area under the receiver operating characteristic curve of the LA-PSS as a potential indicator pathway of LVDD was 67% [95% confidence interval (CI), 62-72], and 75% (95% CI, 70-80), when the indeterminate pattern was included. The decreased LA-PSS made it possible to reclassify patients with an indeterminate pattern of diastolic function in 96% of cases. These results support the potential role of LA-PSS as an additional parameter for the diagnosis of LVDD in patients with normal EF, and may be integrated into the guidelines for routine evaluation of patients.

Uncoupling protein 1-driven Cre (Ucp1-Cre) is expressed in the epithelial cells of mammary glands and various non-adipose tissues

ObjectiveUncoupling protein 1 (UCP1), a mitochondrial protein responsible for nonshivering thermogenesis in adipose tissue, serves as a distinct marker for thermogenic brown and beige adipocytes. Ucp1-Cre mice are thus widely used to genetically manipulate these thermogenic adipocytes. However, evidence suggests that UCP1 may also be expressed in non-adipocyte cell types. In this study, we investigated the presence of UCP1 expression in different mouse tissues that have not been previously reported. MethodsWe employed Ucp1-Cre mice crossed with Cre-inducible transgenic reporter Nuclear tagging and Translating Ribosome Affinity Purification (NuTRAP) mice to investigate Ucp1-Cre expression in various tissues of adult female mice and developing embryos. Tamoxifen-inducible Ucp1-CreERT2 mice crossed with NuTRAP mice were used to assess active Ucp1 expression in adult mice. Immunostaining, RNA analysis, and single-cell/nucleus RNA-seq (sc/snRNA-seq) data analysis were performed to determine the expression of endogenous UCP1 and Ucp1-Cre-driven reporter expression. We also investigated the impact of UCP1 deficiency on mammary gland development and function using Ucp1-knockout (KO) mice. ResultsUcp1-Cre expression was observed in the mammary glands within the inguinal white adipose tissue of female Ucp1-Cre; NuTRAP mice. Ucp1-Cre was activated during embryonic development in various tissues, including mammary glands, as well as in the brain, kidneys, eyes, and ears, specifically in epithelial cells in these organs. However, Ucp1-CreERT2 showed no or only partial activation in these tissues of adult mice, indicating the potential for low or transient expression of endogenous Ucp1. While sc/snRNA-seq data suggest potential expression of UCP1 in mammary epithelial cells in adult mice and humans, Ucp1-KO female mice displayed normal mammary gland development and function. ConclusionsOur findings reveal widespread Ucp1-Cre expression in various non-adipose tissue types, starting during early development. These results highlight the importance of exercising caution when interpreting data and devising experiments involving Ucp1-Cre mice.

Atrial fibrillation induced by carbon monoxide poisoning: Case report

Background: Carbon monoxide (CO) poisoning is known to have direct toxic effects on the cardiovascular system, including the potential to cause arrhythmias by prolonging the QTc interval. The arrhythmogenic properties of CO are believed to be attributed to its impact on cardiac membranes. Case Presentation: This case report presents the clinical course and management of a 21-year-old male who presented to the Emergency Department (ED) with an altered level of consciousness following exposure to carbon monoxide while cooking on a gas cylinder in a closed room. The patient had no history of chronic medical illness and was a non-smoker. Physical examination revealed stable vital signs, clear breath sounds, and a lax, soft, and non-tender abdomen. Laboratory investigations showed elevated troponin levels indicative of cardiac muscle injury but normal potassium levels. ECG revealed atrial fibrillation with a fast ventricular rate and transient ST elevation. The patient received high flow oxygen. The carboxyhemoglobin level decreased significantly after high-flow oxygen administration, confirming the successful treatment of carbon monoxide poisoning. Echocardiography and coronary angiography demonstrated normal cardiac function and ruled out coronary artery disease, respectively. The patient received high-flow oxygen therapy, continuous cardiac monitoring, and supportive care during hospitalization. Following stabilization and restoration of sinus rhythm, the patient was discharged in stable condition. Conclusion: This case highlights the importance of prompt recognition and management of carbon monoxide poisoning, as well as the need for careful evaluation of cardiac function in such cases. The patient responded well to high-flow oxygen therapy, leading to a decrease in the carboxy hemoglobin level and resolution of symptoms. Timely recognition and appropriate management of carbon monoxide poisoning are crucial in preventing adverse cardiac events and ensuring a favorable outcome for the patient.

Adipocyte-specific inactivation of NAMPT, a key NAD+ biosynthetic enzyme, causes a metabolically-unhealthy lean phenotype in female mice during aging.

Nicotinamide adenine dinucleotide (NAD+) is a universal coenzyme regulating cellular energy metabolism in many cell types. Recent studies have demonstrated the close relationships between defective NAD+ metabolism and aging and age-associated metabolic diseases. The major purpose of the present study was to test the hypothesis that NAD+ biosynthesis, mediated by a rate-limiting NAD+ biosynthetic enzyme, nicotinamide phosphoribosyltransferase (NAMPT), is essential for maintaining normal adipose tissue function and whole-body metabolic health during the aging process. To this end, we provided in-depth and comprehensive metabolic assessments for female adipocyte-specific Nampt knockout (ANKO) mice during aging. We first evaluated body fat mass in young (≤ 4-month-old), middle aged (10 to 14-month-old), and old (≥ 18-month-old) mice. Intriguingly, adipocyte-specific Nampt deletion protected against age-induced obesity without changing energy balance. However, data obtained from the hyperinsulinemic euglycemic clamp procedure demonstrated that, despite the lean phenotype, old ANKO mice had severe insulin resistance in skeletal muscle, heart, and white adipose tissue (WAT). Old ANKO mice also exhibited hyperinsulinemia and hypoadiponectinemia. Mechanistically, loss of Nampt caused marked decreases in WAT gene expression of lipogenic targets of peroxisome proliferator-activated receptor gamma (PPARγ) in an age-dependent manner. In addition, administration of a PPARγ agonist rosiglitazone restored fat mass and improved metabolic abnormalities in old ANKO mice. In conclusion, these findings highlight the importance of the NAMPT-NAD+-PPARγ axis in maintaining functional integrity and quantity of adipose tissue, and whole-body metabolic function in female mice during aging.

An overview of qualitative and quantitative platelet abnormalities in schistosomiasis.

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis.

Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.

Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors

Inducing necroptosis in cancer cells has emerged as an effective strategy to overcome drug resistance. However, while organic small molecules have been extensively studied for this purpose, metal-based compounds have received relatively little attention as triggers of necroptosis. The development of ruthenium (II) hybrid compounds, particularly those containing triazene (Ru-TRZ), highlights a novel avenue for modulating necroptotic cell death. Here we show that incorporating a methyltriazene moiety, a known alkylating warhead, confers superior mitochondrial-targeting properties and enhances cell death compared to amide-containing counterparts. Ru-hybrid TRZ2 exhibits also antitumor efficacy against in vivo drug-resistant cancer cells. Mechanistically, we demonstrate that Ru-TRZ hybrids induce apoptosis. In addition, by activating downstream RIPK3-driven cell death, TRZ2 proficiently restrains normal mitochondrial function and activity, leading to cancer cell necroptosis. Finally, TRZ2 synergizes anti-proliferative activity and cell death effects induced by conventional drugs. In conclusion, Ru-TRZ2 stands as a promising ruthenium-based chemotherapeutic agent inducing necroptosis in drug resistant cancer cells.

Evaluation of split renal dysfunction using radiomics based on magnetic resonance diffusion-weighted imaging.

Accurate and noninvasive assessment of split renal dysfunction is crucial, while there is lack of corresponding method clinically. To investigate the feasibility of using diffusion-weighted imaging (DWI)-based radiomics models to evaluate split renal dysfunction. We enrolled patients with impaired and normal renal function undergoing renal DWI examination. Glomerular filtration rate (GFR, mL/min) was measured using 99mTc-DTPA scintigraphy, which is reference standard of GFR measurement. The kidneys were classified into normal (GFR ≥40), mildly impaired (20≤ GFR<40), moderately impaired (10≤ GFR<20), and severely impaired (GFR<10) renal function groups. Optimized subsets of radiomics features were selected from renal DWI images and radiomics scores (Rad-score) calculated to discriminate groups with different renal function. The radiomics model (Rad-score based) was developed in a training cohort and validated in a test cohort. Evaluations were conducted on the discrimination, calibration, and clinical application of the method. The final analysis included 330 kidneys. Logistic regression was used to develop three radiomics models, model A, B, and C, which were used to distinguish normal from impaired, mild from moderate, and moderate from severe renal function, respectively. The area under the curve of the three models were 0.822, 0.704, and 0.887 in the training cohort and 0.843, 0.717, and 0.897 in the test cohort, respectively, indicating efficient discrimination performance. DWI-based radiomics models have potential for evaluating split renal dysfunction and discriminating between normal and impaired renal function groups and their subgroups.

A novel mutation of DNA2 regulates neuronal cell membrane potential and epileptogenesis.

Mesial temporal lobe epilepsy (MTLE) is one of the most intractable epilepsies. Previously, we reported that mitochondrial DNA deletions were associated with epileptogenesis. While the underlying mechanism of mitochondrial DNA deletions during epileptogenesis remain unknown. In this study, a novel somatic mutation of DNA2 gene was identified in the hippocampal tissue of two MTLE patients carrying mitochondrial DNA deletions, and this mutation decreased the full-length expression of DNA2 protein significantly, aborting its normal functions. Then, we knocked down the DNA2 protein in zebrafish, and we demonstrated that zebrafish with DNA2 deficiency showed decreased expression of mitochondrial complex II-IV, and exhibited hallmarks of epileptic seizures, including abnormal development of the zebrafish and epileptiform discharge signals in brain, compared to the Cas9-control group. Moreover, our cell-based assays showed that DNA2 deletion resulted in accumulated mitochondrial DNA damage, abnormal oxidative phosphorylation and decreased ATP production in cells. Inadequate ATP generation in cells lead to declined Na+, K+-ATPase activity and change of cell membrane potential. Together, these disorders caused by DNA2 depletion increased cell apoptosis and inhibited the differentiation of SH-SY5Y into branched neuronal phenotype. In conclusion, DNA2 deficiency regulated the cell membrane potential via affecting ATP production by mitochondria and Na+, K+-ATPase activity, and also affected neuronal cell growth and differentiation. These disorders caused by DNA2 dysfunction are important causes of epilepsy. In summary, we are the first to report the pathogenic somatic mutation of DNA2 gene in the patients with MTLE disease, and we uncovered the mechanism of DNA2 regulating the epilepsy. This study provides new insight into the pathogenesis of epilepsy and underscore the value of DNA2 in epilepsy.

Therapeutic targeting of TP53 nonsense mutations in cancer

Mutations in the TP53 tumor suppressor gene occur with high prevalence in a wide range of human tumors. A significant fraction of these mutations (around 10%) are nonsense mutations, creating a premature termination codon (PTC) that leads to the expression of truncated inactive p53 protein. Induction of translational readthrough across a PTC in nonsense mutant TP53 allows the production of full-length protein and potentially restoration of normal p53 function. Aminoglycoside antibiotics and a number of novel compounds have been shown to induce full-length p53 in tumor cells carrying various TP53 nonsense mutations. Full-length p53 protein generated by translational readthrough retains the capacity to transactivate p53 target genes and trigger tumor cell death. These findings raise hopes for efficient therapy of TP53 nonsense mutant tumors in the future.

A study on the application of radiomics based on cardiac MR non-enhanced cine sequence in the early diagnosis of hypertensive heart disease

BackgroundThe prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension.Methods132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity.ResultsThe feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively.ConclusionsRadiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells.

A cell is a dynamic system in which various processes occur simultaneously. In particular, intra- and intercellular signaling pathway crosstalk has a significant impact on a cell's life cycle, differentiation, proliferation, growth, regeneration, and, consequently, on the normal functioning of an entire organ. Hippo signaling and YAP/TAZ nucleocytoplasmic shuttling play a pivotal role in normal development, homeostasis, and tissue regeneration, particularly in lung cells. Intersignaling communication has a significant impact on the core components of the Hippo pathway and on YAP/TAZ localization. This review describes the crosstalk between Hippo signaling and key lung signaling pathways (WNT, SHH, TGFβ, Notch, Rho, and mTOR) using lung cells as an example and highlights the remaining unanswered questions.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

BACKGROUND Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5’-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26 . However, the positive regulators of ANKRD26 are still unknown. AIM To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26 . Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26 . Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26 . Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26 . Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5’-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26 . In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

BackgroundRenal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes.MethodsThis retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression.ResultsThe prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only.ConclusionsClinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.