The number of drugs developed by non-global companies, including biotech start-ups, has increased; however, their characteristics and impact on global regulatory approval are not well understood. Using a public database, we identified new molecular entities (NMEs) approved for hematologic malignancies in the US from January 2011 to December 2022. They were divided into those submitted by non-global companies (non-global group) and those by global companies (global group).
View Article and Find Full Text PDFAssociational effects, whereby plants influence the biotic interactions of their neighbors, are an important component of plant-insect interactions. Plant chemistry has been hypothesized to mediate these interactions. The role of chemistry in associational effects, however, has been unclear in part because the diversity of plant chemistry makes it difficult to tease apart the importance and roles of particular classes of compounds.
View Article and Find Full Text PDFIdiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I analogs can cause thyroid gland swelling and abnormal thyroid function.
View Article and Find Full Text PDFChronic thromboembolic pulmonary hypertension (CTEPH) is designated as an intractable disease by the Ministry of Health, Labour and Welfare of Japan, and has an extremely poor prognosis if untreated. Surgical pulmonary endarterectomy is the curative treatment for cases in which the organized thrombi are located in the central part of the pulmonary artery, but there had been no effective treatment for cases in which the thrombi are located in the peripheral part of the pulmonary artery. Recently, balloon pulmonary angioplasty (BPA), a transcatheter procedure to dilate stenotic or occluded lesions in the peripheral pulmonary artery, has been rapidly developed.
View Article and Find Full Text PDFObjective: Since novel therapeutic agents for malignancies are developed rapidly mainly in the US, the interval of approval timing between the US and other countries is an important issue. Among them, drugs for hematologic malignancies tended to have a particularly long delays in Japan, but its characteristics have not been fully understood. This study assessed the approval delays in drugs for hematologic malignancies in Japan compared with that in Europe.
View Article and Find Full Text PDFIn flowering plants, pollination, pollen tube growth, and fertilization are regarded as the first hierarchical processes of producing offspring. However, their independent contributions to fruit set and development remain unclear. In this study, we examined the effect of three different types of pollen, intact pollen (IP), soft X-ray-treated pollen (XP) and dead pollen (DP), on pollen tube growth, fruit development and gene expression in "Micro-Tom" tomato.
View Article and Find Full Text PDFBackground/aim: The treatment strategy for metastatic upper tract urothelial carcinoma (mUTUC) is currently based on the evidence from metastatic urinary bladder cancer (mUBC). However, some reports have shown that the outcomes of UTUC differ from those of UBC. Therefore, we retrospectively analyzed the prognosis of patients with mUBC and mUTUC treated with first-line platinum-based chemotherapy.
View Article and Find Full Text PDFJasmonates (JAs) are plant hormones with crucial roles in development and stress resilience. They activate MYC transcription factors by mediating the proteolysis of MYC inhibitors called JAZ proteins. In the absence of JA, JAZ proteins bind and inhibit MYC through the assembly of MYC-JAZ-Novel Interactor of JAZ (NINJA)-TPL repressor complexes.
View Article and Find Full Text PDFA 57-year-old male patient with relapsed/refractory diffuse large B-cell lymphoma received 4 courses of Pola-BR (polatuzumab vedotin-bendamustine-rituximab). After treatment, stem cell collection with G-CSF and plerixafor successfully yielded 4.2×10 cells/kg of CD34-positive cells.
View Article and Find Full Text PDFVolatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl β-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure.
View Article and Find Full Text PDFHigh mannose-type free N-glycans with a single N-acetyl-D-glucosamine (GlcNAc) residue at the reducing end (GN1-HMT-FNGs) are produced by cytosolic endo-β-N-acetylglucosaminidase (EC:3.2.1.
View Article and Find Full Text PDFResponses of plant cells to reactive oxygen species (ROS), e.g., reprogramming of defense genes or progression of cell death, should include the ROS signal transmission to target proteins, but the biochemistry of this process is largely unknown.
View Article and Find Full Text PDFOne of the characteristic aspects of odour sensing in humans is the activation of olfactory receptors in a slightly different manner in response to different enantiomers. Here, we focused on whether plants showed enantiomer-specific response similar to that in humans. We exposed Arabidopsis seedlings to methanol (control) and (+)- or (-)-borneol, and found that only (+)-borneol reduced the root length.
View Article and Find Full Text PDFThe pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors.
View Article and Find Full Text PDFGreen leaf volatiles (GLVs), the common constituents of herbivore-infested plant volatiles (HIPVs), play an important role in plant defense and function as chemical cues to communicate with other individuals in nature. Reportedly, in addition to endogenous GLVs, the absorbance of airborne GLVs emitted by infested neighboring plants also play a major role in plant defense. For example, the exclusive accumulation of ()-3-hexenyl vicianoside in the HIPV-exposed tomato plants occurs by the glycosylation of airborne ()-3-hexenol (Z3HOL); however, it is unclear how plants process the other absorbed GLVs.
View Article and Find Full Text PDFPulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice.
View Article and Find Full Text PDFGlandular trichomes (GTs) are epidermal structures that provide the first line of chemical defense against arthropod herbivores and other biotic threats. The most conspicuous structure on leaves of cultivated tomato (Solanum lycopersicum) is the type-VI GT (tVI-GT), which accumulates both flavonoids and volatile terpenoids. Although these classes of specialized metabolites are derived from distinct metabolic pathways, previous studies with a chalcone isomerase 1 (CHI1)-deficient mutant called anthocyanin free (af) showed that flavonoids are required for terpenoid accumulation in tVI-GTs.
View Article and Find Full Text PDFBackground: It is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries.
View Article and Find Full Text PDFFrameshifts in the Calreticulin (CALR) exon 9 provide a recurrent driver mutation of essential thrombocythemia (ET) and primary myelofibrosis among myeloproliferative neoplasms (MPNs). Here, we generated knock-in mice with murine Calr exon 9 mimicking the human CALR mutations, using the CRISPR-Cas9 method. Knock-in mice with del10 [Calr mice] exhibited an ET phenotype with increases of peripheral blood (PB) platelets and leukocytes, and accumulation of megakaryocytes in bone marrow (BM), while those with ins2 (Calr mice) showed a slight splenic enlargement.
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