Search

Abstract. We report on a 4-month-old infant with mitral valve injury that was induced by percutaneous balloon valvuloplasty for severe aortic valve stenosis. Three-dimensional echocardiography revealed a laceration at the [...]

Abstract. We successfully implanted a coronary stent via a modified Blalock-Taussig shunt to relieve stenosis of the left pulmonary artery in an infant with pulmonary atresia and ventricular septal defect. [...]

Abstract. We report a 9-year-old boy with progressive heart failure due to effusive-constrictive pericarditis. The patient was successfully rescued by extensive surgical removal of the thickened pericardium. The histopathological examination [...]

Key Message: Lily R3-MYB transcription factors are involved in negative regulation to limit anthocyanin accumulation in lily flowers and leaves and create notable color patterns on ectopically expressed petunia flowers. In eudicots, both positive and negative regulators act to precisely regulate the level of anthocyanin accumulation. The R3-MYB transcription factor is among the main factors repressing anthocyanin biosynthesis. Although, in monocots, the positive regulators have been well characterized, the negative regulators have not been examined. Two R3-MYBs, LhR3MYB1 and LhR3MYB2, which were identified in lily transcriptomes, were characterized in this study to understand the regulatory mechanisms of anthocyanin biosynthesis. LhR3MYB1 and LhR3MYB2 had a C2 suppressor motif downstream of a single MYB repeat; the similar amino acid motif appears only in AtMYBL2 among the eudicot R3-MYB proteins. Stable and transient overexpression of LhR3MYB1 and LhR3MYB2 in tobacco plants showed suppression of anthocyanin biosynthesis by both; however, suppression by LhR3MYB2 was stronger than that by LhR3MYB1. In the lily plant, the LhR3MYB2 transcript was detected in leaves with light stimulus-induced anthocyanin accumulation and in pink tepals. Although LhR3MYB1 was expressed in some, but not all tepals, its expression was not linked to anthocyanin accumulation. In addition, LhR3MYB1 expression levels in the leaves remained unchanged by the light stimulus, and LhR3MYB1 transcripts predominantly accumulated in the ovaries, which did not accumulate anthocyanins. Thus, although LhR3MYB1 and LhR3MYB2 have an ability to repress anthocyanin accumulation, LhR3MYB2 is more strongly involved in the negative regulation to limit the accumulation than that by LhR3MYB1. In addition, the overexpression of LhR3MYB2 generated notable color patterns in petunia flowers; thus, the usefulness of the LhR3MYB genes for creating unique color patterns by genetic engineering is discussed.

Non-culprit lesion-related coronary events are a significant concern in patients with coronary artery disease (CAD) undergoing coronary intervention. Since several studies using intra-coronary imaging modalities have reported a high prevalence of vulnerable plaques in non-culprit lesions at the initial coronary event, the immediate stabilization of these plaques by intensive pharmacological regimens may contribute to the reduction in the adverse events. Although current treatment guidelines recommend the titration of statin and other drugs to attain the treatment goal of low-density lipoprotein cholesterol (LDL-C) level in patients with CAD, the early prescription of strong LDL-C lowering drugs with more intensive regimen may further reduce the incidence of recurrent cardiovascular events. In fact, several studies with intensive regimen have demonstrated a higher percentage of patients with the attainment of LDL-C treatment goal in the early phase following discharge. In addition to many imaging studies showing plaque stabilization by LDL-C lowering drugs, several recent reports have shown the efficacy of early statin and proprotein convertase subtilisin/kexin type 9 inhibitors on the immediate stabilization of non-culprit coronary plaques. To raise awareness regarding this important concept of immediate plaque stabilization and subsequent reduction in the incidence of recurrent coronary events, the term 'Drug Intervention' has been introduced and gradually applied in the clinical field, although a clear definition is lacking. The main target of this concept is patients with acute coronary syndrome as a higher prevalence of vulnerable plaques in non-culprit lesions in addition to the worse clinical outcomes has been reported in recent imaging studies. In this article, we discuss the backgrounds and the concept of drug intervention., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in daily practice. The CVIT-DEFER registry is a prospective multicenter registry enrolling consecutive patients with angiographically intermediate coronary stenosis for whom FFR measurement is clinically indicated. The treatment strategy determined from angiographic findings alone and the strategy selected after FFR measurement were compared. Data on the treatment strategy were obtained for 3093 subjects. The average age of these subjects was 69.5 ± 10.2 years and 73.8 % were men. The majority had stable coronary artery disease, including 60.4 % with stable angina pectoris. The treatment strategy based on angiographic findings was medical management in 34.5 %, percutaneous coronary intervention (PCI) in 63.5 %, and coronary artery bypass grafting in 2.1 %. The FFR was ≤0.8 in 1566 lesions (42.2 %). After FFR measurement, medical treatment was changed to revascularization in 19.7 %, while PCI was switched to medical treatment in 57.4 % at the lesion level. As a result, reclassification of the treatment strategy at the patient level was done in 39.0 % of the patients. Revascularization was frequently switched to medical treatment after FFR measurement. These findings support the clinical utility of employing FFR data to guide selection of PCI.

The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clinically relevant coronary artery stenosis. However, mismatch in assessing the severity of coronary stenosis between coronary angiography and the FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)-DEFER registry is a prospective multicenter registry study that has enrolled 3,228 consecutive patients among 3,804 patients with angiographically moderate coronary artery lesions in whom FFR analysis was clinically indicated. The demographic and angiographic parameters associated with an FFR ≤0.8 were analyzed, and the incidence of discrepancy between the angiographic severity of coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609 (42.9%) lesions were categorized as showing 50% stenosis, 1,882 lesions (50.2%) as 75% stenosis, and 257 lesions (6.9%) as 90% stenosis. Angiographic-FFR "mismatch," which was defined as visual stenosis ≥75% with FFR >0.80, was found in 43.4% of lesions, while reverse angiographic mismatch (visual stenosis <75% with FFR ≤0.8) was found in 23.2%. The independent predictors for "angiographic-FFR mismatch" were the presence of percutaneous coronary intervention (PCI) history, one-vessel disease, non-left anterior descending artery (LAD) location, non-diffuse lesion, non-ostial lesion, and non-tandem lesion. Conversely, "reverse angiographic mismatch" was independently associated with the multivessel disease, LAD location, and diffuse lesion. The FFR is not only influenced by luminal stenosis but also by coronary artery morphology and the amount of jeopardized myocardium. Angiographic-FFR mismatch is frequent in patients with moderate coronary stenosis, which suggests the clinical importance of using physiological assessment to guide PCI.

Whether the lesion morphology and associated interventional procedures for the left main coronary artery disease (LMCA) could affect clinical outcome is still controversial. Therefore, we examined the impact of lesion morphology and associated procedures on clinical and angiographic outcomes of stenting for the LMCA. Among 7,660 patients with coronary intervention registered, we analyzed early angiographic results of 228 patients (179 men, mean age 69.4 years) concerned with LMCA lesions. In 121 out of 228 patients having long-term angiographic results, we examined the occurrence of major adverse coronary events (MACE) particularly in terms of the presence of acute coronary syndrome (ACS), the kind of stents, bear metal or drug eluting, the lesion morphology and associated procedures. Early angiographic success rate of LMCA stenting was 100 %, and clinical success rate was 94.3 %. During follow-up period for 3 years, MACE was observed in 17 patients. Under these conditions, multiple stenting (p < 0.01) and complicated procedures such as such as Y-stent, T-stent and crush stent (p < 0.01) were listed as risks for MACE, although there was no statistical difference in kinds of stent. Multivariate analysis demonstrated the significant disadvantage of complicated procedures using the bear metal stent on the occurrence of MACE (p < 0.01). These results demonstrate that the complicated procedures have great impact on clinical and angiographic outcomes after stenting for LMCA lesions, and suggest the simple procedure with a single stent for LMCA lesions in the present cohort. Whether the presence of ACS can affect the prognosis should further be sought.

Adult T-cell leukemia/lymphoma (ATLL), an infrequent malignancy resultant from human T-cell lymphotropic virus type I (HTLV-1), exhibits a spectrum of phenotypes, encompassing acute, smoldering, lymphomatous, and chronic variants, each bearing distinct clinical presentations. The preponderant acute manifestation is characterized by hypercalcemia, systemic manifestations, organomegaly, and dermatological eruptions. Conversely, the chronic phenotype is typified by lymphocytosis and/or cutaneous eruptions, while smoldering ATLL assumes an asymptomatic course. Immunocompromise afflicts ATLL patients, heightening their vulnerability to opportunistic infections that frequently intricately intertwine with disease progression. Therefore, an early diagnosis is crucial to manage the disease appropriately. While conventional chemotherapeutic regimens have shown limited success, especially in acute and lymphoma types, recent studies suggest that allogeneic stem cell transplantation might enhance treatment results because it has shown promising outcomes in some patients. Novel therapeutics, such as interferon and monoclonal antibodies, have also shown promise, but more research is needed to confirm their efficacy. Moreover, the identification of biomarkers for ATLL and genetic changes in HTLV-1 infected cells has led to the development of targeted therapies that have shown remarkable success in clinical trials. These targeted therapies have the potential to offer a more personalized approach to the treatment of ATLL. The aim of our review is to elaborate on conventional and novel therapies and the efficiency of mentioned treatments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Antiplatelet therapy could prevent stent thrombosis, but may be associated with an increased risk of bleeding. Recent studies have revealed that bleeding complications are relatively frequent in patients with acute coronary syndromes. Our aim was to describe the current status of antiplatelet therapy for Japanese patients with acute myocardial infarction (AMI). The Japan AMI (J-AMI) registry is a prospective observational study that has enrolled 2,030 consecutive patients with stent thrombosis elevation myocardial infarction (STEMI) admitted to 213 participating Japanese institutions. Current antiplatelet therapy for STEMI was assessed, and the occurrence of bleeding complications (based on GUSTO bleeding criteria) and stent thrombosis was also evaluated. Additionally, the clinical course after bleeding episodes was investigated. Percutaneous coronary intervention (PCI) was done in 97.2% of the patients, using a drug-eluting stent in 30% and a bare metal stent in 63% of PCI cases. A 300-mg loading dose of clopidogrel followed by its administration at 75 mg/day with aspirin was the current standard treatment for Japanese STEMI patients. In-hospital bleeding complications occurred in 1.9%, especially in patients with severe clinical features or a history of cerebrovascular disease. Moderate to severe bleeding complications were associated with 10 deaths. The in-hospital stent thrombosis (ST) rate was 1.47 %, and loading with clopidogrel prior to PCI was significantly less frequent in patients who developed ST (P < 0.001). In conclusion, the J-AMI registry revealed that severe symptoms of STEMI increased the risk of bleeding, while delay of clopidogrel loading was associated with ST. These findings suggest the need for treatment based on risk stratification to improve the balance between the beneficial and adverse effects of antiplatelet therapy in Japanese STEMI patients.

The door-to-balloon time and total ischemic time are important predictors of the outcome in patients with ST elevation myocardial infarction (STEMI) receiving primary angioplasty, but the current situation in Japan is unknown. The Japan Acute Myocardial Infarction registry is a prospective observational study of 2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time from symptom onset to hospital arrival, door-to-balloon time, and in-hospital outcome were assessed. Data were compared between patients treated during regular hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the treated cases. The median symptom onset-to-door time (25th and 75th percentiles) was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and mean procedural time was 98 ± 51 min. The on-call catheterization team performed 48.5 % of the procedures. There was no significant difference of door-to-balloon time between the patients treated after hours and those treated during regular hours. The cardiac mortality rate was 3.2 %, and it increased with longer door-to-balloon times (P = 0.03). The relationship between total ischemic time and cardiac mortality showed 2 peaks, with a trough at 5 h. Median door-to-balloon time was <90 min and was not longer in after hours cases. These findings suggest that Japanese institutions can provide primary angioplasty within an acceptable time frame.

A 68-year-old man with acute ST elevation myocardial infarction (STEMI) underwent emergent coronary angiography which showed total occlusion in the proximal right coronary artery (RCA). Gray-scale intravascular ultrasound (IVUS) revealed the culprit lesion was expansively remodeled and contained ruptured and echolucent plaques with spotty calcification, whereas thin-capped fibroatheroma and a large amount of scattered necrotic core were observed by virtual histology (VH)-IVUS. After stent implantation in the proximal RCA under a filter protection, filter-no-reflow phenomenon occurred and thrombus-like defect was observed in the mid RCA. Under these conditions, VH-IVUS detected a large amount of scattered necrotic core in the mid RCA. We suggest scattered necrotic core detected by VH-IVUS may be associated with slow-flow phenomenon during percutaneous coronary intervention in our patient with STEMI.

Background: A variety of procedures for reconstructing the spine following the removal of spinal cord and cauda equina tumours have been developed to prevent postoperative spinal deformities and nerve entrapment. The purpose of this paper is to introduce a new reconstructive procedure based on rotational laminoplasty and to report preliminary results in a small series., Method: The trough is drilled at the border of the laminae and articular processes and the ligamentum flavum is resected on its cephalocaudal aspect, so the vertebral arch can be separated as a single mass. After tumour resection, the vertebral arch is removed en bloc with the laminae, and is rotated 90 degrees and placed on the articular facets and fixed using suture passing through holes drilled in the bone., Findings: One man and six women underwent rotational laminoplasty following resection of spinal or cauda equina tumours. Operative exposure was good and permitted complete resection. Patients did well postoperatively from both spine-surgical and neurosurgical points of view. Computed tomography documented a bony union with preservation of widely patent spinal canal., Interpretation: Rotational laminoplasty affords a satisfactory operative exposure for the resection of large, complex lesions. It creates a widely patent, stable spinal canal easily, without the need for special tools.

Background: Separation of the posterior ring apophysis of an adjacent vertebral body can sometimes accompany lumbar intervertebral disc herniation. The condition can be both difficult to detect in conventional radiographs and is somewhat controversial to treat. Although there is general agreement on the frequent need for surgery, there is no consensus on the choice of operation. One procedure, posterior lumbar interbody fusion (PLIF), has never been examined for effectiveness., Method: Computed tomography (CT) either or with discography (CTD) was compared to plane radiographs and magnetic resonance imaging (MRI) for its ability to reveal the fragmentation. Five cases were identified and the severity of the condition evaluated using the Japanese Orthopaedic Association's Assessment of Treatment for Low Back Pain (JOA score). The fragments were removed by impaction with a shoe shaped device and posterior lumbar interbody fusion (PLIF) was performed using autogenous iliac crest bone. A second evaluation using the JOA score was performed after a 4 to 5 year follow-up., Findings: CT identified the separation in all 5 cases while plain films showed the defect in two and MRI in none. JOA scores prior to surgery were between 5 and 19 (mean, 13) and between 25 and 29 (mean, 27.4) at follow-up. The scores represented a recovery of 80% to 100%t (mean, 89.4)., Interpretation: CT and CT discography (CTD) are the diagnostic tools of choice for detecting this condition. Posterior lumbar interbody fusion (PLIF) is an effective procedure for patients who have low back pain due to lumbar disc herniation accompanied by a separation of the posterior ring apophysis.

To understand the genetic background of two floral anthocyanin pigmentation traits, anthocyanin pigmentation in the flower tepals and spot formation, in the Asiatic hybrid lily (2n = 24), segregation of the two traits among 96 F(1) plants derived from a cross between commercial cultivars 'Montreux' and 'Connecticut King' were investigated. 'Montreux' has anthocyanin pigmentation in the tepals with many spots, and 'Connecticut King' has flowers with carotenoid pigmentation without spots. The F(1) plants with or without anthocyanin pigment in the tepals segregated with a 1:1 segregation ratio, indicating that a single gene controls anthocyanin pigmentation in the tepals. The number of spots per square centimeter of all tepals showed continuous distribution in the F(1) plants. To map the loci for the two anthocyanin pigmentation traits, molecular linkage maps in the Asiatic hybrid lily were constructed using a double pseudo-testcross strategy, with the same F(1) plants used for phenotypic evaluation, and 212 PCR-based DNA markers. The trait for anthocyanin pigmentation in tepals was used as a trait marker. The map of 'Montreux' comprised 95 markers in 26 linkage groups, and the map of 'Connecticut King' used 119 markers in 24 linkage groups. The total map lengths were 867.5 and 1,114.8 cM, respectively. The trait locus for anthocyanin pigmentation in the tepals was between markers ASR35-180 and P506-40 in linkage group 1 of the 'Montreux' map with a map distance of 1.2 cM and 2.6 cM, respectively. A single-point analysis of quantitative trait loci (QTLs) for tepal spot number identified two putative QTLs in linkage groups 1 and 19 of the 'Connecticut King' map. One putative QTL in linkage group 19 explained 64% of the total phenotypic variation. Because both putative QTLs were mapped on the linkage map of 'Connecticut King' that has no spots, dominant alleles of them might suppress spot formation.

To elucidate the validity and reproducibility of the use of intravenous echo-contrast agent in the evaluation of left ventricular (LV) performance, we measured LV volume and ejection fraction (EF) in 42 patients with triggered harmonic contrast imaging (THCI), compared with continuous harmonic imaging without contrast agent (CHI) and with cineventriculography (CVG). In 10 of 42 patients, THCI improved LV border delineation which could not be obtained even with CHI. LV end-diastolic, end-systolic volumes and EF by both CHI and THCI correlated well with those by CVG. Although LV volumes are underestimated, THCI lessened the mean differences to about in half, compared with CHI. The observer variabilities obtained using THCI were smaller than those by CHI. These results indicate the validity of LV enhancement and the measurement of EF using THCI. We suggest that this method noninvasively provides more accurate LV systolic function with the acceptable reproducibility.

Lacto-N-tetraose (Galbeta1 -3GlcNAcbeta1-3Galbeta1-4Glc, LNT) and lacto-N-neotetraose (Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc, LNnT) were enzymatically synthesized by consecutive additions of GlcNAc and Gal residues to lactose. Lacto-N-triose II (GlcNAcbeta1-3Galbeta1-4Glc) was prepared first by the transfer of GlcNAc from UDP-GlcNAc to lactose by beta-1,3-N-acetylglucosaminyltransferase from bovine serum. The resulting lacto-N-triose II was converted into LNT and LNnT utilizing two kinds of beta-D-galactosidase-mediated transglycosylations. Thus, beta-D-galactosidase from Bacillus circulans ATCC31382 induced regioselective galactosyl transfer from o-nitrophenyl beta-D-galactoside to the OH-3" position of lacto-N-triose II, and commercially available beta-D-galactosidase from B. circulans to the OH-4" position of lacto-N-triose II. These convenient processes are suitable for large-scale preparations of LNT and LNnT. As another method, LNT was directly synthesized from lactose as an initial substance, utilizing lacto-N-biosidase (Aureobacterium sp. L-101)-mediated transglycosylation with Galbeta1-3GlcNAcbeta-pNP donor.

Genetic variation in protoplast-derived rice (Oryza sativa L.) plants was characterized using first and second generation selfed progenies. A total of 133 regenerated plants were obtained from ten protoplasts of the japonica rice cultivar Nipponbare. Sixty two regenerated plants which set enough seeds for the subsequent field tests at the next generation and were derived from five protoplasts were selected, and their selfed seeds were used as the first selfed-seed progeny (Pt(1) generation). Fifteen plants were selected from each of the 15 Pt(1) lines, and their selfed seeds were used for tests at the Pt(2) generation. Thirty seven Pt(1) lines (60%) segregated plants with detrimental mutant characters of yellowgreen phenotype, dwarf stature, dense and short panicle, or low seed fertility. According to the segregation patterns in the lines having mutated plants among those originated from the same protoplasts, the stages of mutation induction were estimated. Additionally, five quantitative traits were changed in almost all Pt(1) and Pt(2) lines. Varied quantitative traits of heading date, number of spikelets per panicle, and seed fertility, were in a heterozygous state. However, culm and panicle lengths showed high uniformity, whereas reduced culm and panicle lengths were caused by mutational changes in polygenes and/or multiple genes.

Random amplified polymorphic DNA (RAPD) markers were utilized for the identification of Lilium species and inter-specific hybrids. The optimum annealing temperature of the polymerase chain reaction (PCR) for the RAPD assay in Lilium was 54 °C, which is relatively higher than the temperature used for other genera reported by previous researchers. Among 76 primers used to amplify genomic DNA by PCR, 18 primers (24%) generated polymorphic DNA fragments in Lilium species and hybrids. Cultivars were also identified by RAPD markers. Some amplified fragments were unique to species of each section and to hybrids derived from these species; that is, they were the section-specific DNA markers. Sections, Sinomartagon, Leucolirion b, Leucolirion a and Archelirion could be identified by 6 section-specific markers amplified with five primers. Seven inter-section hybrids showed the section-specific bands of both parental sections, indicating that these markers would be useful for identifying the parental sections of inter-section hybrids.

This study was to evaluate the impact of leaflet trimming strategy on the hemodynamic behaviors of the aortic valve after reconstructive surgery, and give recommendations based on design of experiment (DOE) and in vitro studies. An in vitro hemodynamic test was performed on the simulated surgical model to quantify the efficacy of conventional reconstructive surgery. The very same computational model was built and verified, on which the full factorial DOE was carried out to summarize the correlations between leaflet trimming parameters and valve hemodynamic characteristics. Hemodynamic characteristics of the valve substitute were significantly associated with leaflet trimming parameters. The total regurgitant and transvalvular regurgitant of the valve substitute were reduced by 27.44% and 13.61% after optimization of the leaflet design. Synthetic use of in vitro tests and DOE study based on computational models helped improve outcomes of the reconstruction of aortic valve by reducing free edge length and increasing commissure height and leaflet height., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ischemic diseases are characterized by obstruction of blood flow to the respective organs, of which ischemia of the heart and brain are the most prominent manifestations with shared pathophysiological mechanisms and risk factors. While most revascularization therapies aim to restore blood flow, this can be challenging due to the limited therapeutic window available for treatment approaches. For a very long time, mesenchymal stromal cells have been used to treat cerebral and cardiac ischemia. However, their application is restricted either by inefficient mode of delivery or the low cell survival rates following implantation into the ischemic microenvironment. Nonetheless, several studies are currently focusing on using of mesenchymal stromal cells engineered to overexpress therapeutic genes as a cell-based gene therapy to restore angiogenesis. This review delves into the utilization of MSCs for angiogenesis and the applications of engineered MSCs for the treatment of cardiac and cerebral ischemia. Moreover, the safety issues related to the genetic modification of MSCs have also been discussed., Competing Interests: Declarations Conflicts of Interest The authors declare that they have no conflict of interest. Ethics Approval Not applicable. Consent to Participate Not applicable. Consent for Publication All the authors gave their consent for the publication., (© 2024. The Author(s).)

The heart is an organ with a low ability to renew and repair itself. MSCs have cell surface markers such as CD45 - , CD34 - , CD31 - , CD4 + , CD11a + , CD11b + , CD15 + , CD18 + , CD25 + , CD49d + , CD50 + , CD105 + , CD73 + , CD90 + , CD9 + , CD10 + , CD106 + , CD109 + , CD127 + , CD120a + , CD120b + , CD124 + , CD126 + , CD140a + , CD140b + , adherent properties and the ability to differentiate into cells such as adipocytes, osteoblasts and chondrocytes. Autogenic, allogeneic, normal, pretreated and genetically modified MSCs and secretomes are used in preclinical and clinical studies. MSCs and their secretomes (the total released molecules) generally have cardioprotective effects. Studies on cardiovascular diseases using MSCs and their secretomes include myocardial infraction/ischemia, fibrosis, hypertrophy, dilated cardiomyopathy and atherosclerosis. Stem cells or their secretomes used for this purpose are administered to the heart via intracoronary (Antegrade intracoronary and retrograde coronary venous injection), intramyocardial (Transendocardial and epicardial injection) and intravenous routes. The protective effects of MSCs and their secretomes on the heart are generally attributed to their differentiation into cardiomyocytes and endothelial cells, their immunomodulatory properties, paracrine effects, increasing blood vessel density, cardiac remodeling, and ejection fraction and decreasing apoptosis, the size of the wound, end-diastolic volume, end-systolic volume, ventricular myo-mass, fibrosis, matrix metalloproteins, and oxidative stress. The present review aims to assist researchers and physicians in selecting the appropriate cell type, secretomes, and technique to increase the chance of success in designing therapeutic strategies against cardiovascular diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dermatomyositis is a rare, autoimmune systemic disorder of unknown aetiology that presents as a constellation of clinical symptoms and signs primarily affecting skin and muscles. Patients with dermatomyositis can present with rare "non-canonical" manifestations. Focal or generalised oedema is an infrequent and often overlooked symptom of the disease, while spontaneous intramuscular haemorrhage is an even rarer and under-recognised, life-threatening complication that constitutes a medical emergency for clinical physicians. There are no known predisposing factors able to predict which patients will develop this complication and specific instructions considering treatment approach are currently lacking. Herein, we present a case of a patient with dermatomyositis complicated by both anasarca and spontaneous intramuscular haemorrhage. In order to raise awareness and timely diagnosis of such patients, we provide a review of the relevant literature and of the cases reported this far., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Taste aversion learning is universal. In animals, a single presentation of a novel food substance followed hours later by visceral illness causes animals to avoid that taste. This is known as bait-shyness or the Garcia effect. Humans demonstrate this by avoiding a certain food following the development of nausea after ingesting that food ('Sauce Bearnaise effect'). Here, we show that the pond snail Lymnaea stagnalis is capable of the Garcia effect. A single 'pairing' of a novel taste, a carrot slurry followed hours later by a heat shock stressor (HS) is sufficient to suppress feeding response elicited by carrot for at least 24 h. Other food tastes are not suppressed. If snails had previously been exposed to carrot as their food source, the Garcia-like effect does not occur when carrot is 'paired' with the HS. The HS up-regulates two heat shock proteins (HSPs), HSP70 and HSP40. Blocking the up-regulation of the HSPs by a flavonoid, quercetin, before the heat shock, prevented the Garcia effect in the snails. Finally, we found that snails exhibit Garcia effect following a period of food deprivation but the long-term memory (LTM) phenotype can be observed only if the animals are tested in a food satiated state.

Key Message: LhGST, an anthocyanin-related GST gene, was identified from Asiatic hybrid lilies. Expression and functional analyses demonstrated that LhGST might be involved in anthocyanin sequestration in lily tepals. Anthocyanins are responsible for the pink, red and purple pigmentation of flowers in Asiatic hybrid lilies, synthesized at the cytoplasmic surface of the endoplasmic reticulum (ER) and then transported to the vacuole. To date, the mechanism involved in the intracellular transport of anthocyanins in lilies has not been well elucidated. Here, full-length glutathione S-transferase gene (LhGST) was identified from lilies. Expression analysis revealed that LhGST was positively correlated with anthocyanin accumulation. Phylogenetic tree analysis showed that LhGST clustered with other anthocyanin-related GSTs in the same phi clade. Moreover, functional complementation of an Arabidopsis tt19 mutant demonstrated that LhGST might be involved in anthocyanin accumulation in lily tepals. Additionally, according to phenotype analysis, LhGST was found to be correlated with the transport of anthocyanin in lilies by virus-induced gene silencing (VIGS) assay. In addition, cis-element analysis of the LhGST promoter showed the presence of ABA-, auxin-, MeJA-, gibberellin-, light-, and stress-responsive elements and an MYB recognition site (MRS, CCGTTG). Yeast one-hybrid and dual-luciferase report assays revealed that the promoter of LhGST was activated by LhMYB12-lat, which is a key R2R3-MYB transcription factor that regulates anthocyanin biosynthesis in lilies. In conclusion, our results revealed that LhGST plays a key role in anthocyanin transport and accumulation in the tepals of lilies.

Zeugodacus cucurbitae and Z. tau are two major fruit fly pests of cucurbitaceous plants in the tropical and subtropical regions. The former species has a broader host range and wider world distribution than the latter. With global climate change, Z. tau shows great potential for geographical expansion with several invasion records in recent years. Males of both species are attracted to cue lure (CL) (and raspberry ketone (RK), a deacetyl derivative of CL), a common male lure used in fruit fly population detection, monitoring and control programs. Males of both species are also known to respond to zingerone (ZN), which are produced by some rainforest orchids. Previous studies have shown that fruit fly-male lure interactions are unique to species and lure types, and significantly impact the success of a lure-based fruit fly control program. We seek to compare the attraction of Z. cucurbitae and Z. tau males to CL, RK and ZN via Probit behavioral assays. Our results showed that CL is more attractive to Z. cucurbitae and Z. tau males than RK, while ZN is a poor lure for both species. Attraction Z. tau to CL is slightly lower than Z. cucurbitae, but the former is at least 1.71 times less attractive to RK than the latter. Together with published information on species' sexual development, our current study indicates a lure-based control program via male annihilation technique for Z. tau will be more challenging than Z. cucurbitae and should incorporate other integrated pest management strategies for a desirable outcome., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: Fine mapping of the maize QTL qSRC3, responsible for red silk, uncovered the candidate gene ZmMYB20, which encodes an R2R3-MYB transcription factor, has light-sensitive expression, and putatively regulates genes expression associated with anthocyanin biosynthesis. Colorless silk is a key characteristic contributing to the visual quality of fresh corn intended for market distribution. Nonetheless, the identification of Mendelian trait loci and associated genes that control silk color has been scarce. In this study, a F 2 population arising from the hybridization of the single-segment substitution line qSRC3 MT1 with red silk, carrying an introgressed allele from teosinte (Zea mays ssp. mexicana), and the recurrent maize inbred line Mo17, characterized by light green silk, was utilized for fine mapping. We found that the red silk trait is controlled by a semi-dominant genetic locus known as qSRC3, and its expression is susceptible to light-mediated inhibition. Moreover, qSRC3 explained 68.78% of the phenotypic variance and was delimited to a 133.2 kb region, which includes three genes. Subsequent expression analyses revealed that ZmMYB20 (Zm00001d039700), which encodes an R2R3-MYB transcription factor, was the key candidate gene within qSRC3. Yeast one-hybrid and dual-luciferase reporter assays provided evidence that ZmMYB20 suppresses the expression of two crucial anthocyanin biosynthesis genes, namely ZmF3H and ZmUFGT, by directly binding to their respective promoter regions. Our findings underscore the significance of light-inhibited ZmMYB20 in orchestrating the spatial and temporal regulation of anthocyanin biosynthesis. These results advance the production of colorless silk in fresh corn, responding to the misconception that fresh corn with withered colored silk is not fresh and providing valuable genetic resources for the improvement of sweet and waxy maize., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm., (© 2023. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Growth hormone and insulin like growth factor-1 plays an important role in the regulation of body composition and metabolism. Growth Hormone is released from the pituitary through a specific G-protein coupled receptor (GPCR) called growth hormone secretagogue receptor 1a expressed in the hypothalamus. Ghrelin is a peptide hormone released from the cells in the stomach, which stimulates appetite and food intake in mammals, regulates gut motility, gastric acid secretion, taste sensation, circadian rhythm, learning and memory, oxidative stress, autophagy, glucose metabolism etc. When the release of the endogenous ligand GHSR-1a, i.e., ghrelin is malfunctioned or stopped, external substitutes are administrated to induce the stimulation of growth hormone and appetite. A class of compound known as ghrelin receptor agonists are developed as an external substitute of ghrelin for regulation and stimulation of growth hormone in frailty, for body weight gain, muscle mass gain, prevention of cachexia and for the treatment of chronic fatigue syndromes. Capromorelin [Entyce™ (Aratana Therapeutics, Leawood, KS, USA)] is the only FDA (Food and Drug Administration) approved (May 2016) drug used for stimulating appetite in dogs and was marketed in the fall of 2017. In 2020, USFDA approved Capromorelin [Elura™ (Elanco US Inc.)] for the management of weight loss in chronic kidney disease of cats. This article reviews the discovery of the ghrelin receptor agonist capromorelin, its efficacy, safety, clinical applications and aims to delineate its further scope of use in veterinary practice., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The Garcia effect is a unique form of conditioned taste aversion which requires that a novel food stimulus be followed sometime later by a sickness state associated with the novel food stimulus. The long-lasting associative memory resulting from the Garcia effect ensures that organisms avoid toxic foods in their environment. Considering its ecological relevance, we sought to investigate whether a brief encounter (5 min) with a novel, appetitive food stimulus can cause a persisting long-term memory (LTM) to form that would in turn block the Garcia effect in Lymnaea stagnalis. Furthermore, we wanted to explore whether that persisting LTM could be modified by the alteration of microRNAs via an injection of poly-L-lysine (PLL), an inhibitor of Dicer-mediated microRNA biogenesis. The Garcia effect procedure involved two observations of feeding behavior in carrot separated by a heat stress (30 °C for 1 h). Exposing snails to carrot for 5 min caused a LTM to form and persist for 1 week, effectively preventing the Garcia effect in snails. In contrast, PLL injection following the 5-min carrot exposure impaired LTM formation, allowing the Garcia effect to occur. These results provide more insight into LTM formation and the Garcia effect, an important survival mechanism., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Characterizations in terms of fractals are typically employed for systems with complex and multiscale descriptions. A prominent example of such systems is provided by the human brain, which can be idealized as a complex dynamical system made of many interacting subunits. The human brain can be modeled in terms of observable variables together with their spatio-temporal-functional relations. Computational intelligence is a research field bridging many nature-inspired computational methods, such as artificial neural networks, fuzzy systems, and evolutionary and swarm intelligence optimization techniques. Typical problems faced by means of computational intelligence methods include those of recognition, such as classification and prediction. Although historically conceived to operate in some vector space, such methods have been recently extended to the so-called nongeometric spaces, considering labeled graphs as the most general example of such patterns. Here, we suggest that fractal analysis and computational intelligence methods can be exploited together in neuroscience research. Fractal characterizations can be used to (i) assess scale-invariant properties and (ii) offer numeric, feature-based representations to complement the usually more complex pattern structures encountered in neurosciences. Computational intelligence methods could be used to exploit such fractal characterizations, considering also the possibility to perform data-driven analysis of nongeometric input spaces, therby overcoming the intrinsic limits related to Euclidean geometry., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The pond snail Lymnaea stagnalis exhibits various forms of associative learning including (1) operant conditioning of aerial respiration where snails are trained not to open their pneumostome in a hypoxic pond water environment using a weak tactile stimulus to their pneumostome as they attempt to open it; and (2) a 24 h-lasting taste-specific learned avoidance known as the Garcia effect utilizing a lipopolysaccharide (LPS) injection just after snails eat a novel food substance (carrot). Typically, lab-inbred snails require two 0.5 h training sessions to form long-term memory (LTM) for operant conditioning of aerial respiration. However, some stressors (e.g., heat shock or predator scent) act as memory enhancers and thus a single 0.5 h training session is sufficient to enhance LTM formation lasting at least 24 h. Here, we found that snails forming a food-aversion LTM following Garcia-effect training exhibited enhanced LTM following operant condition of aerial respiration if trained in the presence of the food substance (carrot) they became averse to. Control experiments led us to conclude that carrot becomes a 'sickness' risk signal and acts as a stressor, sufficient to enhance LTM formation for another conditioning procedure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is characterized by poor treatment response and low survival time. The current clinical treatment for advanced PDAC is still not effective. In recent years, the research and application of immunotherapy have developed rapidly and achieved substantial results in many malignant tumors. However, the translational application in PDAC is still far from satisfactory and needs to be developed urgently. To carry out the study of immunotherapy, it is necessary to fully decipher the immune characteristics of PDAC. This review summarizes the recent progress of the tumor microenvironment (TME) of PDAC and highlights its link with immunotherapy. We describe the molecular cues and corresponding intervention methods, collate several promising targets and progress worthy of further study, and put forward the importance of integrated immunotherapy to provide ideas for future research of TME and immunotherapy of PDAC., (© 2022. Springer Nature Switzerland AG.)

Chitin, the second most abundant biopolymer on earth after cellulose, is composed of β-1,4-N-acetylglucosamine (GlcNAc) units. It is widely distributed in nature, especially as a structural polysaccharide in the cell walls of fungi, the exoskeletons of crustaceans, insects, and nematodes. However, the principal commercial source of chitin is the shells of marine or freshwater invertebrates. Microbial chitinases are largely responsible for chitin breakdown in nature, and they play an important role in the ecosystem's carbon and nitrogen balance. Several microbial chitinases have been characterized and are gaining prominence for their applications in various sectors. The current review focuses on chitinases of microbial origin, their diversity, and their characteristics. The applications of chitinases in several industries such as agriculture, food, the environment, and pharmaceutical sectors are also highlighted., (© 2022. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

In recent years, photocatalysts are becoming attractive to researchers in exploring their application for treatment of air pollutants. Exposure to ultra-violet visible (UV-VIS) light on photocatalysts often makes them active in decomposing various toxic materials into less or environment-friendly products. Thus, identification, as well as simple synthesis and processing of photocatalysts, could ultimately lead to technologies for the cost-effective mitigation of environmental hazards. A bibliometric analysis has been carried out here to understand and assess the development in photocatalyst research. The data retrieved from the Scopus database on the topic for 2000-2020 were analyzed to investigate the research activities of the past to foresight the future. Various facets of bibliometry were investigated to produce this holistic article. The contribution of various countries, institutions, and authors were investigated. Numerous facets of photocatalyst such as types of photocatalysts, their modification through metal and non-metal doping, their pollutants treatment potency, types of reactors for photocatalysis, factors influencing treatment performance, and models used for designing reactors were examined. In brevity, substantial growth was observed in the last two decades. Contribution of China, the USA, Japan, and India were notable. Chinese universities contributed majorly to the research. Applied Catalysis B: Environmental Journal was the topic's main journal and Titanium dioxide was the hotspot in photocatalytic research. The research development, problem disclosure, adopted strategies, and materials explored on the photocatalysis for air pollution treatment over recent years across the world could be insightful to the researchers and eventually will be beneficial to formulate new research strategies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hypercortisolism is one of the most common endocrine diseases in dogs. In humans, it is clearly associated with a higher risk of cardiovascular events, but studies in dogs are scarce. To investigate the arrhythmogenic risk of dogs with naturally-occurring hypercortisolism (NOHC), indices of variability and instability of the QT interval were retrospectively studied in 38 dogs with NOHC and prospectively studied in 12 healthy dogs: variance (QTv), total instability (TI), short-term (STI) and long-term (LTI), and mean (QTm). Except for QTm, all parameters studied were higher in the NOHC group than in the control group. In addition, STI and QTv showed moderate positive correlation with left ventricle wall thickness. The NOHC group was subdivided according to cortisol suppression pattern in the low-dose dexamethasone suppression test. All electrocardiographic indices of partial and absent suppression patterns were numerically higher than healthy dogs. QTv and TI were lower in the control group than in both NOHC subgroups. LTI and STI were lower in the CG than in the group with the partial suppression pattern. There was no statistical difference between sex groups in any of the electrocardiographic parameters studied. This result might indicate that the etiology of NOHC, and its consequent influence on hypothalamus-pituitary-adrenal axis could interfere on the heterogeneity of ventricular repolarization parameters in different ways, especially in the short-term and the long-term stability; however further studies are necessary to understand the role of cortisol on electrical instability in dogs., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Trust and religiosity have been individually linked to better health outcomes, but little existing research examines how they may combine to shape health. Drawing on data from the 6th and most recent wave of the World Values Survey, we examine the relationship between particularized and generalized social trust, two dimensions of religiosity (religious attendance and one's belief in the importance of God), and self-rated health across 27 countries. Findings from multilevel models suggest that trust tends to be higher in more religiously pluralistic national contexts, while religiosity in these contexts helps individuals maintain good health. In particular, a higher importance of God (but not religious attendance) can offset the negative health effects of holding low trust in strangers and non-family members (generalized trust), but only in highly pluralistic national contexts. We conclude by offering future research directives that may shed light on the cultural complexities of the various national contexts and their religious compositions., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study evaluated whether optical frequency domain imaging (OFDI) accurately distinguish between fibroatheroma (FA) and pathological intimal thickening (PIT) compared with histopathology., Methods: A total of 631 histological cross-sections from 14 autopsy hearts were analyzed for the comparison between OFDI and histological images. Of those, 190 (30%) sections were diagnosed with PIT and 120 (19%) with FA. The OFDI signal attenuation rate was calculated from an exponential. The lipid length was measured longitudinally by detection of sequential OFDI frames within a plaque segment containing lipids. The lipid arc was measured with a protractor centered in the center of the lumen. The fibrous cap thickness was defined as the minimum thickness of the signal rich band overlying PIT and FA., Results: There was no significant difference in the OFDI signal attenuation rate between FA and PIT (3.09 ± 1.04 versus 2.79 ± 1.20, p = 0.13). However, the lipid length was significantly longer, the maximum lipid arc was significantly larger, and the fibrous cap thickness was significantly thinner in FA than in PIT (7.5 [4.3-10.3] mm versus 4.3 [2.7-5.8] mm, p < 0.0001, 125 [101-174]° versus 96 [74-131]°, p < 0.0001, and 220 [167-280] µm versus 260 [190-332] µm, p = 0.019)., Conclusions: This study revealed OFDI may have the potential capability for discriminating FA from PIT based on the longitudinal and circumferential extent of lipid plaque, although the OFDI signal attenuation rate was similar between FA and PIT., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The localization of myocardial 18F-fluorodeoxyglucose (FDG) uptake affecting long-term clinical outcomes has not been elucidated in patients with corticosteroid-naïve cardiac sarcoidosis (CS)., Objectives: This study sought to investigate the localization of myocardial FDG uptake on positron emission tomography (PET) and myocardial perfusion abnormality to predict adverse events (AEs) for a long-term follow-up in patients with corticosteroid-naïve CS., Methods: Consecutive 90 patients with clinical suspicion of CS who underwent FDG-PET imaging to assess for inflammation were enrolled. AEs were defined as a composite of sustained ventricular tachycardia (VT), heart transplantation, and all-cause death, which were ascertained by medical records, defibrillator interrogation, and telephone interviews., Results: Of 90 patients, 42 patients (mean age 62.9 ± 12.0 years; 76.2% females) were confirmed active cardiac involvement. Over a median follow-up of 4.9 years, 15 patients with CS experienced AEs including 6 sustained ventricular tachycardias (VT) and 9 deaths. Cox proportional-hazards model after adjustment for left ventricular systolic dysfunction revealed that FDG uptake in the right ventricle (RV) or basal anterolateral area of the left ventricle (LV) with myocardial perfusion abnormality was predictive of AEs., Conclusions: FDG uptake in the RV or basal anterolateral area of the LV with myocardial perfusion abnormality provides long-term prognostic risk stratification in patients with corticosteroid-naïve CS., (© 2021. American Society of Nuclear Cardiology.)

Necroptosis is a programmed necrosis that is mediated by receptor-interacting protein kinases RIPK1, RIPK3 and the mixed lineage kinase domain-like protein, MLKL. Necroptosis must be strictly regulated to maintain normal tissue homeostasis, and dysregulation of necroptosis leads to the development of various inflammatory, infectious, and degenerative diseases. Ubiquitylation is a widespread post-translational modification that is essential for balancing numerous physiological processes. Over the past decade, considerable progress has been made in the understanding of the role of ubiquitylation in regulating necroptosis. Here, we will discuss the regulatory functions of ubiquitylation in necroptosis signaling pathway. An enhanced understanding of the ubiquitylation enzymes and regulatory proteins in necroptotic signaling pathway will be exploited for the development of new therapeutic strategies for necroptosis-related diseases., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plenty of epidemiological approaches have been explored to detect the effects of environmental and socioeconomic factors on acute myocardial infarction (AMI) mortality. Whereas, identifying the influence of potential affecting factors on AMI mortality based on a spatial epidemiological perspective was strongly desired. Moreover, the interaction effects of two potential factors on the diseases were always neglected previously. Here, the Geodetector and geographically & temporally weighted regression model (GTWR) combined with multi-source spatiotemporal datasets were introduced to quantitatively determine the relationship between AMI mortality and potential influencing factors across Xi'an during 2014-2016. Besides, Moran's I was adopted to diagnose the spatial autocorrelation of AMI mortality. Some findings were achieved. The number of AMI mortality cases increased from 5075 in 2014 to 6774 in 2016. Air pollutants, meteorological factors, economic status, and topography factors exhibited a significant effect on AMI mortality. The AMI mortality demonstrated an obvious spatial autocorrelation feature during 2014-2016. POP and PE represented the most obvious impact on AMI mortality, respectively. Moreover, the interaction of any two factors was larger than that of the single factor on AMI mortality, and the factors with the strongest interaction vary according to lag groups and ages. The effects of factors on AMI mortality were POP (- 628.925) > PE (140.102) > RD (79.145) > O 3 (- 58.438) > E&#95;NH 3 (42.370) for male, and POP (- 751.206) > RD (132.935) > E&#95;NH 3 (58.758) > PE (- 45.434) > O 3 (- 21.256) for female, respectively. This work reminds the local government to continuously control air pollution, strengthen urban planning, and improve the health care of the rural areas for alleviating AMI mortality. Meanwhile, the scheme of the current study supplies a scientific reference for examining the effects of potential impact factors on related diseases using the spatial epidemiological perspective., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mangiferin is a glycosylated xanthone widely distributed in nature, which exhibits wide pharmacological activities, highlighting its anti-cancer properties. Mangiferin interferes with inflammation, lipid, and calcium signaling, which selectively inhibits multiple NFkB target genes as interleukin-6, tumor necrosis factor, plasminogen, and matrix metalloproteinase, among others. In this work, the interactions of this polyphenol with MMP-9 and NF-κβ are characterized by using computational chemistry methods. The results show MMP-9 inhibition by mangiferina is characterized for the interact with the catalytic Zn atom through a penta-coordinate structure. It is also demonstrated through a strong charge transfer established between mangiferin and Zn in the QM/MM study. Concerning the mangiferin/NF-κβ system, the 92.3% of interactions between p50 sub-unity and DNA are maintained with a binding energy of - 8.04 kcal/mol. These findings indicate that mangiferin blocks the p50-p65/DNA interaction resulting in the loss of the functions of this hetero-dimeric member and suggesting inhibition of the cancer progression. Experimental results concerning the anti-cancer properties of mangiferin show that this natural compound can inhibit selectively MMP-9 and NF-ƙβ. Although the anti-tumor properties of mangiferin are well defined, its molecular mechanisms of actions are not described. In this work, a computational study is carried out to characterize the interactions of mangiferin with these molecular targets. The results obtained corroborate the anti-proliferative and anti-apoptotic activity of mangiferin and provide a depiction of its mechanisms of action., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fractional flow reserve and instantaneous wave-free ratio are widely accepted and recommended in Western and Japanese guidelines for appropriate percutaneous coronary intervention. There are, however, many differences in clinical situations between Japan and Western countries. Therefore, the Task Force on coronary physiology of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) has proposed an expert consensus document to summarize current evidence and suggest the practical use of physiological lesion assessment in Japan., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Human T cell leukemia virus type 1 (HTLV-1) is responsible for adult T cell leukemia (ATL); however, molecular and cellular mechanisms underlying HTLV-1-induced leukemogenesis are unclear. BCL6 oncogene is involved in cancer progression and a preferred target of anti-cancer treatments. Here, we aimed to evaluate BCL6 expression and the effects of BCL6 inhibitor (FX1) on HTLV-1-infected T cell lines. BCL6 expression was higher in HTLV-1-infected T cell lines than that in uninfected T cell lines. BCL6 was localized mostly in the nucleus. The virus oncoprotein Tax induced BCL6 mRNA expression in T cells, whereas BCL6 knockdown reduced HTLV-1-infected T cell proliferation; thus, confirmed the association of BCL6 with cancer progression. Further, FX1 efficiently inhibited the cell growth and survival of HTLV-1-infected T cell lines in a dose- and time-dependent manner. The decreased levels of cell cycle regulatory proteins (phosphorylated retinoblastoma protein, cyclin-dependent kinase 4, cyclin D2 and c-Myc) and the increased levels of BCL6 target proteins (p21, p27 and p53) showed that FX1 arrested cell cycle at the G1 phase. Apoptosis was induced concomitantly with Bak upregulation and downregulation of survivin, Bcl-xL and Mcl-1, as well as with the activation of caspase-3, -8, -9 and poly(ADP-ribose) polymerase. FX1 also inhibited NF-κB and Akt signaling pathways. These events were because of the induction of the activity of cell cycle checkpoint proteins and relief of direct repression of the targets of cell cycle checkpoint proteins. Thus, BCL6 might be considered a novel target for ATL treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Previous qualitative research has described that previous misdiagnoses may reduce patient and their families' trust in healthcare., Objective: To quantify the associations between patients or family members' misdiagnosis experiences and trust in their physician., Design: Cross-sectional study., Participants: Adult Japanese people with non-communicable diseases (cancer, diabetes, depression, heart disease, and connective tissue disease), recruited using a web-based panel survey., Main Measures: Surveys assessed the patient and the patient's family's experience with misdiagnosis. Trust in the respondent's current physician was measured using the Japanese version of the 11-item Trust in Physician Scale., Key Results: Among 661 patients (response rate 30.1%), 23.2% had a personal history of misdiagnosis and 20.4% had a family history of misdiagnosis. In a multivariable-adjusted general linear model, patients or a family members' misdiagnosis experiences were associated with lower confidence in their current physician (mean difference -4.3, 95%CI -8.1 to -0.49 and -3.2, 95%CI -6.3 to -0.05, respectively). The impact of having a personal and a family member's experience of misdiagnosis on trust was additive, with no evidence of interaction (P for interaction = 0.494)., Conclusions: The patient's or family members' misdiagnosis experiences reduced trust in the patient's current physicians. Interventions specifically targeting misdiagnosed patients are needed to restore trust., (© 2021. Society of General Internal Medicine.)

Olfactory dysfunction is reported frequently in patients with coronavirus disease 2019. However, an effective treatment for this dysfunction is unknown. The present study evaluated carbamazepine as a treatment option for olfactory dysfunction based on its use in cases of neuralgia, especially of the V cranial nerve. The study included 10 patients with coronavirus disease with olfactory complaints who were part of a cohort of 172 coronavirus disease patients monitored for late neurological manifestations. Carbamazepine was administered for 11 weeks. The adverse effects reported were drowsiness (9/10) and dizziness (2/10); 9 of the 10 patients reported improved olfactory function after carbamazepine treatment. While the role of carbamazepine in the control of post-coronavirus disease olfactory dysfunction could not be confirmed in this study, the satisfactory response observed in most patients in this series suggests that further studies are warranted., (© 2022. Journal of NeuroVirology, Inc.)

Mounting evidence shows that cell therapy provides therapeutic benefits in experimental and clinical settings of chronic heart failure. However, direct cardiac delivery of cells via transendocardial injection is logistically complex, expensive, entails risks, and is not amenable to multiple dosing. Intravenous administration would be a more convenient and clinically applicable route for cell therapy. Thus, we determined whether intravenous infusion of three widely used cell types improves left ventricular (LV) function and structure and compared their efficacy. Rats with a 30-day-old myocardial infarction (MI) received intravenous infusion of vehicle (PBS) or 1 of 3 types of cells: bone marrow mesenchymal stromal cells (MSCs), cardiac mesenchymal cells (CMCs), and c-kit-positive cardiac cells (CPCs), at a dose of 12 × 10 6 cells. Rats were followed for 35 days after treatment to determine LV functional status by serial echocardiography and hemodynamic studies. Blood samples were collected for Hemavet analysis to determine inflammatory cell profile. LV ejection fraction (EF) dropped ≥ 20 points in all hearts at 30 days after MI and deteriorated further at 35-day follow-up in the vehicle-treated group. In contrast, deterioration of EF was halted in rats that received MSCs and attenuated in those that received CMCs or CPCs. None of the 3 types of cells significantly altered scar size, myocardial content of collagen or CD45-positive cells, or Hemavet profile. This study demonstrates that a single intravenous administration of 3 types of cells in rats with chronic ischemic cardiomyopathy is effective in attenuating the progressive deterioration in LV function. The extent of LV functional improvement was greatest with CPCs, intermediate with CMCs, and least with MSCs., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Proviral load (PVL) is one of the determining factors for the pathogenesis and clinical progression of the human T-lymphotropic virus type I (HTLV-1) infection. In the present study, we optimized a sensitive multiplex real-time PCR for the simultaneous detection and quantification of HTLV-1 proviral load and beta-globin gene as endogenous control. The values obtained for HTLV-1 PVL were used to monitor the clinical evolution in HTLV-1-infected individuals. A vector containing cloned DNA targets of the real-time PCR for the beta-globin gene and the HTLV-1pol region was constructed. For the reaction validation, we compared the amplification efficiency of the constructed vector and MT-2 cell line containing HTLV-1. The analytical sensitivity of the reaction was evaluated by the application of a standard curve with a high order of magnitude. PVL assay was evaluated on DNA samples of HTLV-1 seropositive individuals. The construct showed adequate amplification for the beta-globin and HTLV-1 pol genes when evaluated as multiplex real-time PCR (slope = 3.23/3.26, Y-intercept = 40.18/40.73, correlation coefficient r 2 = 0.99/0.99, and efficiency = 103.98/102.78, respectively). The quantification of PVL using the MT-2 cell line was equivalent to the data obtained using the plasmidial curve (2.5 copies per cell). In HTLV-1-associatedmyelopathy/tropical spastic paraparesis patients, PVL was significantly higher (21315 ± 2154 copies/10 5 PBMC) compared to asymptomatic individuals (1253 ± 691 copies/10 5 PBMC). The obtained results indicate that the optimized HTLV-1 PVL assay using plasmidial curve can be applied for monitoring and follow-up of the progression of HTLV-1 disease. The use of a unique reference plasmid for both HTLV-1 and endogenous gene allows a robust and effective quantification of HTLV-1 PVL. In addition, the developed multiplex real-time PCR assay was efficient to be used as a tool to monitor HTLV-1-infected individuals., (© 2022. Journal of NeuroVirology, Inc.)

Key Message: Overexpression of AgMYB12 in celery improved the accumulation of apigenin by interacting with the AgFNS gene. Celery is a common vegetable, and its essential characteristic is medicine food homology. A natural flavonoid and a major pharmacological component in celery, apigenin plays an important role in human health. In this study, we isolated a novel R2R3-MYB transcription factor that regulates apigenin accumulation from the celery cultivar 'Jinnan Shiqin' through yeast one-hybrid screening and designated it as AgMYB12. The AgMYB12 protein was located in the nucleus. It showed transcriptional activation activity and bound specifically to the promoter of AgFNS, a gene involved in apigenin biosynthesis. Phylogenetic tree analysis demonstrated that AgMYB12 belongs to the flavonoid branch. It contains two flavonoid-related motifs, SG7 and SG7-2, and shared a highly conserved R2R3 domain with flavonoid-related MYBs. The homologous overexpression of AgMYB12 induced the up-regulation of AgFNS gene expression and accumulation of apigenin and luteolin in celery. Additionally, the expression levels of apigenin biosynthesis-related genes, including AgPAL, AgCHI, AgCHS, Ag4CL, and AgC4H, increased in transgenic celery plants. These results indicated that AgMYB12 acted as a positive regulator of apigenin biosynthesis and activated the expression of AgFNS gene. The current study provides new information about the regulation mechanism of apigenin metabolism in celery and offers a strategy for cultivating the plants with high apigenin content., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)